記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Introduction

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy. Personal genome analyses have revealed numerous aHUS‐causing variants, mainly complement‐related genes. However, not all aHUS‐causing variants have been functionally validated.

Methods

An exome sequence analysis of a Japanese multiplex family composed of three patients diagnosed with aHUS in infancy and showing frequent relapses clustered in a dominant transmission mode was performed. Protein interaction between the C3d and C‐terminal domains of factor H was analyzed using a quartz crystal microbalance.

Results

Following filtering by heterozygous variants, amino acid substitutions, and allele frequency, the analysis revealed eight rare variants shared by the affected individuals. Variant prioritization listed C3 p.W1034R as the most likely candidate gene mutation in the affected individuals, despite being classified as a variant of uncertain significance. Binding of recombinant C3d harboring 1034R to recombinant short consensus repeats 15 to 20 of factor H was significantly suppressed compared with that of C3 with 1034W.

Conclusion

C3 p.W1034R results in an inherited form of aHUS that often presents with recurrent episodes, possibly because of impaired interactions between the C3d and C‐terminal domains of factor H. Following comprehensive genomic analysis, functional validation of C3 p.W1034R strengthens the molecular basis for aHUS pathophysiology.

DOI： 10.1002/mgg3.2288

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.

DOI： 10.1038/s41588-023-01422-x

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sodium magnetic resonance imaging can non-invasively assess sodium distribution, specifically sodium concentration in the countercurrent multiplication system in the kidney, which forms a sodium concentration gradient from the cortex to the medulla, enabling efficient water reabsorption. This study aimed to investigate whether sodium magnetic resonance imaging can detect changes in sodium concentrations under normal conditions in mice and in disease models such as a mouse model with diabetes mellitus. Methods: We performed sodium and proton nuclear magnetic resonance imaging using a 9.4-T vertical standard-bore super-conducting magnet. Results: A condition of deep anesthesia, with widened breath intervals, or furosemide administration in 6-week-old C57BL/6JJcl mice showed a decrease in both tissue sodium concentrations in the medulla and sodium concentration gradients from the cortex to the medulla. Further, sodium magnetic resonance imaging revealed reductions in the sodium concentration of the medulla and in the gradient from the cortex to the medulla in BKS.Cg-Leprdb+/+ Leprdb/Jcl mice at very early type-2 diabetes mellitus stages compared to corresponding control BKS.Cg-m+/m+/Jcl mice. Conclusions: The kidneys of BKS.Cg-Leprdb+/+ Leprdb/Jcl mice aged 6 weeks showed impairments in the countercurrent multiplication system. We propose the utility of 23Na MRI for evaluating functional changes in diabetic kidney disease, not as markers that reflect structural damage. Thus, 23Na MRI may be a potential very early marker for structures beyond the glomerulus; this may prompt intervention with novel efficacious tubule-targeting therapies.

DOI： 10.34067/KID.0000000000000072

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied. METHODS: We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP. RESULTS: Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06-11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Cardiac disfunctions were significantly associated with the high hANP level. CONCLUSIONS: The hANP level is indicative of both fluid volume and cardiac dysfunction. A threshold hANP level of 100 pg/mL can serve as a predictive marker for AHF and a practical indicator for volume control.

DOI： 10.1007/s10157-023-02333-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We present a family of two female Alport syndrome patients with a family history of impaired glucose tolerance. Whole exome sequencing identified a novel heterozygous variant of COL4A5 NM_033380.3: c.2636 C > A (p.S879*) and a rare variant of GCK NM_001354800.1: c.1135 G > A (p.A379T) as the causes of Alport syndrome and monogenic diabetes, respectively. Two independent pathogenic variants affected the clinical phenotypes. Clinical next-generation sequencing is helpful for identifying the causes of patients' manifestations.

DOI： 10.1038/s41439-023-00233-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m2 or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.

DOI： 10.1038/s10038-022-01094-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

DOI： 10.1159/000527900

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Clinical Investigation  

Inhibitors of the renin-angiotensin system (RAS) are widely used to treat hypertension. Using mice harboring fluorescent cell lineage tracers, single-cell RNA-Seq, and long-term inhibition of RAS in both mice and humans, we found that deletion of renin or inhibition of the RAS leads to concentric thickening of the intrarenal arteries and arterioles. This severe disease was caused by the multiclonal expansion and transformation of renin cells from a classical endocrine phenotype to a matrix-secretory phenotype: the cells surrounded the vessel walls and induced the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis. Ablation of the renin cells via conditional deletion of β1 integrin prevented arteriolar hypertrophy, indicating that renin cells are responsible for vascular disease. Given these findings, prospective morphological studies in humans are necessary to determine the extent of renal vascular damage caused by the widespread use of inhibitors of the RAS.

DOI： 10.1172/jci.insight.154337

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：The American Association of Immunologists  

Antiribosomal P protein (anti-P) autoantibodies commonly develop in patients with systemic lupus erythematosus. We have previously established hybridoma clones producing anti-P mAbs. In this study, we explored the pathogenesis of behavioral disorders induced by anti-P Abs using these mAbs. New Zealand Black × New Zealand White F1, New Zealand White, C57BL/6, and BALB/c mice were treated with 1 mg of anti-P Abs once every 2 wk. The behavioral disorder was evaluated by the tail suspension test, forced swim test, and open field test. Following administration of anti-P Abs, New Zealand Black × New Zealand White F1 and C57BL/6 mice developed depressive behavior and showed increased anxiety with elevated serum TNF-α and IL-6 levels. Anti-P Abs were not deposited in the affected brain tissue; instead, this mood disorder was associated with lower serum and brain tryptophan concentrations. Tryptophan supplementation recovered serum tryptophan levels and prevented the behavioral disorder. TNF-α and IL-6 were essential for the decreased serum tryptophan and disease development, which were ameliorated by treatment with anti-TNF-α neutralizing Abs or dexamethasone. Peritoneal macrophages from C57BL/6 mice produced TNF-α, IL-6, and IDO-1 via interaction with anti-P Abs through activating FcγRs, which were required for disease development. IVIg, which has an immunosuppressive effect partly through the regulation of FcγR expression, also prevented the decrease in serum tryptophan and disease development. Furthermore, serum tryptophan concentrations were decreased in the sera of systemic lupus erythematosus patients with anti-P Abs, and lower tryptophan levels correlated with disease activity. Our study revealed some of the molecular mechanisms of mood disorder induced by anti-P Abs.

DOI： 10.4049/jimmunol.2000260

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Protein-bound uremic toxins (PBUTs) are difficult to remove using conventional dialysis treatment owing to their high protein-binding affinity. As pH changes the conformation of proteins, it may be associated with the binding of uremic toxins. Albumin conformation at pH 2 to 13 was analyzed using circular dichroism. The protein binding behavior between indoxyl sulfate (IS) and albumin was examined using isothermal titration calorimetry. Albumin with IS, and serum with IS, p-cresyl sulfate, indole acetic acid or phenyl sulfate, as well as serum from hemodialysis patients, were adjusted pH of 3 to 11, and the concentration of the free PBUTs was measured using mass spectrometry. Albumin was unfolded at pH < 4 or >12, and weakened interaction with IS occurred at pH < 5 or >10. The concentration of free IS in the albumin solution was increased at pH 4.0 and pH 11.0. Addition of human serum to each toxin resulted in increased free forms at acidic and alkaline pH. The pH values of serums from patients undergoing hemodialysis adjusted to 3.4 and 11.3 resulted in increased concentrations of the free forms of PBUTs. In conclusion, acidic and alkaline pH conditions changed the albumin conformation and weakened the protein binding property of PBUTs in vitro.

DOI： 10.3390/toxins13020116

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ndt/gfaa319

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. METHODS: Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. RESULTS: Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3-30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. CONCLUSIONS: These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.

DOI： 10.1093/ndt/gfaa223

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記述言語：英語  

We report the case of a patient with complement factor H gene variant, who developed thrombotic microangiopathy on a mixed clinical background. A 79-year-old woman was transferred to Sanjo General Hospital for maintenance hemodialysis. She suffered from gastric non-Hodgkin lymphoma about two years ago and received chemotherapy and radiation therapy, leading to complete remission. About 13 weeks prior to her transfer to our hospital, she was referred to another hospital due to acute kidney injury, hemolytic anemia, and thrombocytopenia. Hemodialysis was immediately initiated, after which intravenous methylprednisolone and oral prednisolone were started; however, she became anuric within approximately week. The possibility of thrombotic microangiopathy was examined. However, she was in poor general condition and did not get the consent of her family, so no invasive searches such as a kidney biopsy were performed. Despite the cause of acute kidney insufficiency being unclear, she was transferred to us for maintenance hemodialysis. Her general condition was stable, and her renal function improved; hence, two months after transfer, a kidney biopsy was performed. Her clinical and typical renal histological findings indicated a diagnosis of thrombotic microangiopathy. There was a possible CFH gene of a very rare variant "c.526 T > C (p.Phe176Leu)" in exon 5. She was able to withdraw from hemodialysis therapy two weeks after the initiation of an angiotensin-converting enzyme inhibitor. Based on her clinical course and kidney biopsy findings, she was diagnosed with thrombotic microangiopathy with a very rare CFH variant. To ensure proper treatment choices such as eculizumab, the presence of complement dysregulation should be considered in cases of secondary thrombotic microangiopathy.

DOI： 10.1155/2021/2519918

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

The acyl-CoA synthetase medium-chain family member 2 (Acsm2) gene was first identified and cloned by our group as a kidney-specific "KS" gene. However, its expression pattern and function remain to be clarified. In the present study, we found that the Acsm2 gene was expressed specifically and at a high level in normal adult kidneys. Expression of Acsm2 in kidneys followed a maturational pattern: it was low in newborn mice and increased with kidney development and maturation. In situ hybridization and immunohistochemistry revealed that Acsm2 was expressed specifically in proximal tubular cells of adult kidneys. Data from the Encyclopedia of DNA Elements database revealed that the Acsm2 gene locus in the mouse has specific histone modifications related to the active transcription of the gene exclusively in kidney cells. Following acute kidney injury, partial unilateral ureteral obstruction, and chronic kidney diseases, expression of Acsm2 in the proximal tubules was significantly decreased. In human samples, the expression pattern of ACSM2A, a homolog of mouse Acsm2, was similar to that in mice, and its expression decreased with several types of renal injuries. These results indicate that the expression of Acsm2 parallels the structural and functional maturation of proximal tubular cells. Downregulation of its expression in several models of kidney disease suggests that Acms2 may serve as a novel marker of proximal tubular injury and/or dysfunction.

DOI： 10.1152/ajprenal.00348.2020

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. METHODS: This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation. RESULTS: LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. CONCLUSION: Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. TRIAL REGISTRATION: Trial registration number: jRCTs042180076.

DOI： 10.1007/s10157-020-01959-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type-1 angiotensin II receptor blockade (AT-1RB) on preventing CKD-related fragility fractures and elucidate its pharmacological mechanisms. AT-1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass unchanged. Olmesartan suppressed angiotensin II-dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II-dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT-1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress.

DOI： 10.1002/jbmr.4159

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate units that are linked by phosphoanhydride bonds and is involved in various pathophysiological processes. However, the role of polyP in immune cell dysfunction is not well-understood. In this study, using several biochemical and cell biology approaches, including cytokine assays, immunofluorescence microscopy, receptor-binding assays with quartz crystal microbalance, and dynamic light scanning, we investigated the effect of polyP on in vitro lipopolysaccharide (LPS)-induced macrophage inflammatory response. PolyP up-regulated LPS-induced production of the inflammatory cytokines, such as tumor necrosis factor ?, interleukin-1?, and interleukin-6, in macrophages, and the effect was polyP dose? and chain length?dependent. However, orthophosphate did not exhibit this effect. PolyP enhanced the LPS-induced intracellular macrophage inflammatory signals. Affinity analysis revealed that polyP interacts with LPS, inducing formation of small micelles, and the polyP-LPS complex enhanced the binding affinity of LPS to Toll-like receptor 4 (TLR4) on macrophages. These results suggest that inorganic polyP plays a critical role in promoting inflammatory response by enhancing the interaction between LPS and TLR4 in macrophages.

DOI： 10.1074/jbc.RA119.011763

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: Accumulation of protein-bound uremic toxins (PBUTs) is associated with mortality due to various systemic disorders in patients with chronic kidney disease (CKD), especially in those undergoing dialysis treatment. The clinical outcomes of such patients could be improved by removing sufficient amounts of PBUTs; however, conventional dialysis lacks this ability. We examined the efficacy of activated carbon in adsorbing circulating PBUTs through direct hemoperfusion (DHP) in vitro. Methods: An in vitro blood circulating system was constructed with 8.5 mL blood circulating around a column containing activated carbon (50, 100, or 200 mg). Bovine blood containing a kind of PBUT (at the same concentration as that found in the blood of dialysis patients) and blood from hemodialysis patients (n = 8) were used. After circulation for the designated amount of time, sera were collected and the levels of PBUTs, including indoxyl sulfate (IS), p-cresyl sulfate, indole acetic acid (IAA), phenyl sulfate, and hippuric acid, were analyzed with mass spectrometry. Results: Activated carbon decreased the PBUT level in bovine blood in a dose-dependent manner (e.g., reduction rate of IS: 67.9 +/- 3.8, 83.3 +/- 1.9, and 94.5 +/- 1.1% after 60-min circulation in columns containing 50, 100, and 200 mg activated carbon respectively). IS, PCS, and IAA were dramatically adsorbed by activated carbon from the blood of patients undergoing hemodialysis (pre vs. post 240-min reaction: IS 2.835 +/- 0.876 vs. 0.455 +/- 0.108 mg/dL [p < 0.01], PCS 3.208 +/- 2.876 vs. 0.768 +/- 0.632 mg/dL [p < 0.01], IAA 0.082 +/- 0.045 vs. 0.016 +/- 0.005 mg/dL [p < 0.01]). Conclusion: Activated carbon effectively adsorbed blood PBUTs in vitro. DHP with activated carbon could be a promising strategy for removing circulating PBUTs from the blood of patients with CKD.

DOI： 10.1159/000500014

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掲載種別：研究論文（学術雑誌）  

A 60-year-old male presented with accelerated hypertension, renal insufficiency, proteinuria, and hematuria. Percutaneous kidney biopsy revealed membranoproliferative glomerulonephritis (MPGN) without any immunoglobulin and complement deposition. On performing electron microscopy, deposits with a tubular, organized structure and approximately 60 nm in diameter were detected in the glomerular subendothelial spaces and mesangial areas. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) demonstrated the significantly increased deposition of fibrinogen and fibronectin in glomeruli. Immunohistochemistry and immunoelectron microscopy demonstrated that the deposits were composed of fibrinogen. Here we report a case of cryofibrinogen -associated GN in which LC-MS/MS and immunoelectron microscopy were useful for diagnosis. When MPGN with organized deposits without the deposition of immunoglobulins and complements is diagnosed, we considered the cryofibrinogen-associated GN in one of the differential diagnosis, and even skin symptoms cannot be detected.

DOI： 10.1016/j.ehpc.2018.12.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS INC  

Senescent cells have deleterious effects on the tissue microenvironment through proinflammatory senescence-associated secretory phenotypes; meanwhile, the onset of glomerulonephritis is predominant in younger adults. To clarify the influence of aging on the onset and development of glomerulonephritis, we used a murine model of antibody-mediated nephritis. Sheep nephrotoxic serum was administered in C57BL/6J mice at 12 weeks (adult) or 18 months old (aged) after pre-immunization with sheep IgG. Depositions of sheep IgG and autologous mouse IgG along the glomerular basement membrane and the serum titer of anti-sheep IgG-specific mouse IgG were similar between adult and aged mice. However, kidney injury was depressed in aged mice, accompanied by reduced macrophage infiltration in the glomeruli. The mRNA expression of most chemokines involved in monocyte/macrophage chemotaxis was not different between adult and aged mice, but the cell surface expression of C-C chemokine receptor (CCR) 1 and CCR2 was down-regulated in the monocyte/macrophage lineage cells infiltrating the kidneys of aged nephritic mice. Furthermore, expression of all four isotypes of the Fc gamma receptor (Fc gamma R) was reduced in these cells. Both CCR and Fc gamma R expression were down-regulated in monocyte/macrophage lineage cells, resulting in attenuated glomerular infiltration of these cells and impaired glomerular injury in aged mice.

DOI： 10.1093/gerona/gly019

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/toxins10030124

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background It is well known that atrophic renal changes are associated with chronic kidney disease (CKD) progression, but conventional diagnostic imaging methods such as noncontrast-enhanced computed tomography and magnetic resonance imaging (MRI) have been insufficient for precisely assessing kidney function because they cannot clearly distinguish between the medulla and cortex. Hence, here we used noncontrast-enhanced steady-state free precession (SSFP) MRI with a spatially selective inversion recovery (IR) pulse to improve visibility for renal corti-comedullary differentiation and evaluated the association between morphological parameters and kidney function in patients with CKD.Methods Kidney corticomedullary contrast ratio, cortical and medullary areas, and minimal cortical thickness of 107 patients with CKD G1-G5 were measured using SSFP MRI with a spatially selective IR pulse and the association between these morphological parameters and kidney function were evaluated.Results Corticomedullary contrast ratio was significantly improved on SSFP MRI compared with conventional in-phase T1-weighted gradient-echo MRI and positively correlated with estimated glomerular filtration ratio (eGFR), raw eGFR, and 24-h creatinine clearance. The medullary and cortical areas and minimal cortical thickness also positively correlated with those of kidney functional markers and the age. In patients with CKD and diabetes mellitus (DM), the correlation coefficients between raw eGFR and morphological parameters were higher than those in patients without DM, while minimal cortical thickness was larger in CKD patients with DM with a raw eGFR C 45 mL/min.Conclusion Kidney morphological parameters measured with SSFP MRI were clearly correlated with kidney function in patients with CKD, including those with advanced kidney dysfunction.

DOI： 10.1007/s10157-017-1413-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons for development of uremia-related complications. We examined the PBUT removal ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a representative PBUT, to HICBs was examined in vitro. The HICB column was used in patients undergoing hemodialysis for direct hemoperfusion with a regular hemodialyzer. The serum IS, indole acetic acid (IAA), phenyl sulfate (PhS), and p-cresyl sulfate (PCS) levels were measured before and after passing the column. HICBs adsorbed protein-free (free) IS in a dose- and time-dependent manner in vitro (55.4 +/- 1.4% adsorption of 1 millimolar, 251 mu g/mL, IS for 1 h). In clinical studies, passing the HICB-containing column decreased the serum level of free IS, IAA, PhS, and PCS levels significantly (by 34.4 +/- 30.0%, 34.8 +/- 25.4%, 28.4 +/- 18.0%, and 34.9 +/- 22.1%, respectively), but not protein-bound toxins in maintenance hemodialysis patients. HICBs absorbed some amount of free PBUTs, but the clinical trial to use HICB column did not show effect to reduce serum PBUTs level in hemodialysis patients. Adsorption treatment by means of direct hemoperfusion with regular hemodialysis may become an attractive blood purification treatment to increase PBUT removal when more effective materials to adsorb PBUTs selectively will be developed.

DOI： 10.1111/aor.12961

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Background: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. Methods: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). Results: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. Conclusions: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN.

DOI： 10.1093/ndt/gfw343

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS  

Prolactin is a polypeptide hormone with over 300 separate biologic activities. Its serum level is increased during pregnancy and lactation, and it has been reported that pregnancy and lactation affect drug and steroid metabolism in mice and humans. Several studies reported that pregnancy or lactation influences liver cytochrome P450 (P450) expression and its activity, affecting the biosynthesis of steroids and xenobiotics through growth hormone or sex hormones; however, the role of prolactin as the regulator of liver P450 expression has not been elucidated so far. In the present study, we focused on prolactin as the regulator of expression of liver sex-predominant genes, including P450s. To investigate the role of prolactin in the hepatic gene expressions, pCAGGS expression vector containing mouse prolactin cDNA was transfected by hydrodynamic injection into both male and female mice. Hyperprolactinemia phosphorylated signal transducer and activator of transcription 5 in the liver and augmented female mouse liver mRNA expression of Cyp3a16, Cyp3a41, Cyp3a44, Cyp2b9, and prolactin receptor genes, whose expressions were female-predominant in hepatocytes. Moreover, liver expression of male-predominant genes such as Cyp2d9, Cyp7b1, Mup1, and Alas2 were reduced in male mice with hyperprolactinemia. The serum levels of conventional regulators of hepatic gene expressions, growth hormone, and testosterone were not affected by hyperprolactinemia. We demonstrated that prolactin upregulated female-predominant genes in female mice and downregulated male-predominant genes in male mice. We conjecture that higher concentration of prolactin would alter steroid and xenobiotic metabolisms by modulating hepatic P450 gene expressions during pregnancy and lactation.

DOI： 10.1124/dmd.116.074658

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20-40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established.We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22).There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 +/- 4.4 vs. 9.9 +/- 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02).In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

DOI： 10.1007/s10157-016-1282-8

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

A 36-year-old woman who was undergoing dialysis for end-stage kidney disease (ESKD) was admitted to our hospital with consciousness disorder. She was diagnosed with Budd-Chiari syndrome due to antiphospholipid syndrome at the age of 28 years. Her kidney function and leg edema gradually deteriorated. After initiation of hemodialysis (HD), transient loss of consciousness due to hepatic encephalopathy during HD treatment occurred frequently. Her kidney replacement therapy was changed to online hemodiafiltration (HDF), which dramatically improved her hepatic coma. Compared with HD, HDF contributed to the increase in Fischer's ratio and decrease in tryptophan level, which has a high protein-bound property. This case suggests that HDF may be beneficial for hepatic encephalopathy in ESKD patients by modulating the amino acid profile.

DOI： 10.1007/s13730-015-0209-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The Oxford classification of IgA nephropathy consists of four markers as prognosticators. We retrospectively examined the relevance of extracapillary proliferation involving cellular and fibrocellular crescents (Ex) and arteriolar hyalinosis (A) on the long-term outcome of renal function.A total of 314 Japanese patients who were diagnosed with IgA nephropathy, with 12 months or more of follow-up period were included in this study. A total of 186 patients were with UP aeyen 0.5 g/day. Patients with diabetes mellitus or severe kidney injury (eGFR < 30 ml/min/1.73 m(2)) were excluded. The presence of Ex and A were scored 0 in the absence, and 1 in the presence, of each lesion. The end point was determined as a 50 % reduction in initial eGFR or end-stage renal disease defined as eGFR < 15 ml/min/1.73 m(2).In univariate analyses, the kidney survival rate was significantly lower in patients with Ex1 and A1 if UP aeyen 0.5 g/day. In the patients with UP < 0.5/day, none of the clinical and pathological parameters was determined as a risk factor. In the multivariate model including pathological parameters, Ex1 and A1 were independent risk factors for renal outcome if UP aeyen 0.5 g/day. In those patients treated with RAS-blocker or treated before introduction of methylprednisolone pulse therapy, Ex was the only independent risk factor. In multivariate analysis including clinical parameters, eGFR alone was a risk factor, due to strong correlation with other parameters.Ex and A would be associated with the renal outcome of the patients with UP aeyen 0.5 g/day.

DOI： 10.1007/s10157-015-1185-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

DOI： 10.1007/s10157-015-1216-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Leptin and IL-23 production in NTS nephritis.Leptin, one of the typical adipokines, is reported to promote T(h)17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob (FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative real-time PCR (qRT-PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT-PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/ob mice 7 days after NTS injection. The T(h)17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/ob mice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and T(h)17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.

DOI： 10.1093/intimm/dxv067

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Japan  

There have been several lines of evidences for familial aggregation of IgA nephropathy (IgAN), as well as mesangial deposition of IgA, suggesting that the susceptibility to this disease is genetically controlled. In our institute, family histories of hematuria, end-stage kidney disease, and glomerulonephritis are observed in about 10 % of cases with IgAN, even in those without any significant hereditary nephritis or kidney diseases. Recent large-scale genome-wide association studies (GWAS) of sporadic IgAN have identified multiple susceptibility loci, providing an insight into the genetic architecture of this disease, although each of their individual impact to the development of the disease is still not enough. It has been recognized that most of these loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. Further elucidation of the role of genetic variants underlying IgAN, and hologenetic views of gene variants and environmental factors, would be necessary to understand the precise pathogenic mechanism of IgAN in more detail.

DOI： 10.1007/978-4-431-55588-9_3

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記述言語：日本語   出版者・発行元：一般社団法人 日本耳鼻咽喉科学会  

人体には構成細胞数の10倍以上の微生物が存在し, それらを細菌叢 (マイクロバイオーム) と呼んでいる. 近年, マイクロバイオームは肥満や免疫疾患など人体の健康状態へ影響を及ぼすことが判明しつつある. 口蓋扁桃にも多数の常在細菌が存在し, マイクロバイオームが各種疾患発症に関与している可能性が考えられる. 今回, その基礎となるデータとして, 感染のない小児口蓋扁桃の細菌叢に関し検討した. OSAS に対して手術目的で摘出した小児口蓋扁桃の深部から組織を切り出し, その細菌叢を16S rRNA 解析にて同定し, 細菌培養結果および北欧における Jensen らの報告と比較した. その結果, <i>Haemophilus</i> 属の検出が最多であり, <i>Sphingomonas</i> 属, 嫌気性菌である <i>Prevotella</i> 属, <i>Fusobacterium</i> 属がそれらに続いた. Jensen らの報告では, <i>Streptococcus</i> 属, <i>Neisseria</i> 属, <i>Prevotella</i> 属の順であり, 人種差, 食習慣および採取部位による相違の可能性が考えられた. 培養検査では, <i>Haemophilus</i> 属, 続いて <i>Streptococcus</i> 属, <i>Neiserria</i> 属が多く検出され, <i>Prevotella</i> 属, <i>Fusobacterium</i> 属など嫌気性菌の検出率は低かった. 培養検査では <i>Streptococcus</i> 属との共存下では嫌気性菌の発育が抑制されることが一因と考えられた. 細菌培養検査と異なり, PCR を用いた16S rRNA 解析では難培養性の常在細菌叢に関する検討が可能であり, マイクロバイオームに関する研究には必要不可欠の手技と考える. 今後は成人例との比較や病巣扁桃における口蓋扁桃細菌叢の変化に関して検討を行いたい.

DOI： 10.3950/jibiinkoka.119.29

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その他リンク： http://search.jamas.or.jp/link/ui/2016138976

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本移植学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1 beta, IS 1.0 mM: 101.8 +/- 21.8 pg/mL vs. 0 mM: 7.0 +/- 0.3 pg/mL, TNF-alpha, IS 1.0 mM: 96.6 +/- 11.0 pg/mL vs. 0 mM: 15.1 +/- 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% +/- 7.3% vs. 0 mM: 43.5% +/- 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.

DOI： 10.3390/toxins7083155

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The p.E66Q variant of the alpha-galactosidase A gene (GLA) is frequently found during screening for Fabry disease in dialysis patients in Japan. However, recent reports suggest that the p.E66Q variant is not a disease-causing mutation but is a risk factor for cerebral small-vessel occlusion. To evaluate the role of the p.E66Q in the progression of renal diseases, we performed a genetic association study in patients with chronic kidney disease (CKD).
In this study, we enrolled 1651 chronic hemodialysis and 941 non-dialysis patients who attended medical institutions in the Niigata Prefecture, Japan. The frequency of the p.E66Q allele was compared between hemodialysis and non-dialysis patients, with data from a previously published study of Japanese male newborns. In addition, we compared estimated glomerular filtration rates (eGFR) in the presence or absence of the p.E66Q variant in non-dialysis patients.
Of the 2233 alleles in hemodialysis and 1447 alleles in non-dialysis patients, 21 and nine harbored p.E66Q, respectively. However, p.E66Q allele frequencies did not differ between the two patient groups (0.90 versus 0.62 %, P = 0.35), and no significant difference in p.E66Q allele frequency was observed between male hemodialysis patients and the general Japanese population (0.52 versus 0.63 %, P = 0.67). Moreover, eGFR did not significantly differ between non-dialysis patients with the p.E66Q variant and patients with the wild-type allele (65.5 +/- A 10.7 versus 62.7 +/- A 16.6 mL/min/1.73 m(2), P = 0.69).
This study indicated that the p.E66Q variant of GLA does not affect the progression of CKD.

DOI： 10.1007/s10157-014-0969-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Multiple myeloma (MM) is a plasma-cell neoplasm that can cause renal disorders. Renal lesions in MM can present with a very rare pathological manifestation involving a specific monoclonal immunoglobulin (Ig). We report the case of a 33-year-old woman who had edema, fatigue, elevated serum creatinine levels, hypoalbuminemia, and hypercholesterolemia. She had persistent hematuria and proteinuria lasting 3 years. Serum protein electrophoresis showed an M-spike, and serum immunofixation demonstrated the presence of monoclonal IgG λ. She had proteinuria in the nephrotic range, and a monoclonal λ fragment was present on urine immunofixation. Renal biopsy showed proliferative glomerulonephritis with λ light chain and C3c deposition and inflammatory cell infiltration with CD68. Macrophage lysosomes contained λ light chains, suggesting their partial phagocytosis. She was diagnosed with symptomatic MM and was treated with bortezomib and dexamethasone and an autologous peripheral stem cell transplant conditioned with intravenous melphalan. She achieved a partial response with decreased serum monoclonal protein and improved renal function. This case may be categorized as a monoclonal gammopathy-associated proliferative glomerulonephritis. The biopsy finding of partially phagocytosed Ig λ light chains by macrophages is very rare; this pathological condition is similar to crystal-storing histiocytosis.

DOI： 10.1111/pin.12229

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 53-year-old man with an asymptomatic anterior mediastinal tumor undergoing hemodialysis was referred to our institution. He was diagnosed with thymic basaloid carcinoma based on the findings of a chest tomography-guided biopsy and successfully treated with carboplatin (300 mg/m(2)/day) and paclitaxel (200 mg/m(2)/day) on day 1 for six three-week cycles. To our knowledge, this is the first report regarding the efficiency of a carboplatin dose-definition method based on the body surface area with paclitaxel in a hemodialysis patient. This report may therefore be useful for treating hemodialysis patients who are candidates for carboplatin and paclitaxel therapy.

DOI： 10.2169/internalmedicine.54.3484

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

DOI： 10.1038/ng.3118

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Data regarding renal disease in the elderly (age a parts per thousand yen65 years old) and very elderly (age a parts per thousand yen80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy.From July 2007 to November 2011, all of the elderly native renal biopsy patients who had been registered in the Japan Renal Biopsy Registry (J-RBR; 2802 including 1596 males and 1206 females) were identified. Their data were compared with a control group of 7416 patients who ranged in age from 20 to 64 years old and were registered on the J-RBR over the same period. In addition, the clinical and pathological classifications of 276 very elderly patients were also analyzed.The indications for biopsy were nephrotic syndrome (NS) in 36.2 and 50.7 % of the elderly and the very elderly patients, chronic nephritic syndrome in 31.8 and 17.4 %, and acute kidney injury including rapidly progressive glomerulonephritis in 18.6 and 22.5 %, respectively. Primary glomerular disease was the most frequent diagnosis, followed by MPO-ANCA-positive nephritis, IgA nephropathy (IgAN), and diabetic nephropathy. In primary GN including IgAN, membranous nephropathy (MN) was the most frequent histological type, followed by IgAN and minor glomerular abnormalities. A comparison with the control group showed that MN, MPO-ANCA-positive nephritis, and amyloid nephropathy were more common in the elderly (P < 0.001), and IgAN was less common (P < 0.001). As for nephrotic syndrome in the elderly, MN was the most common histological type, followed by minimal change NS, diabetic nephropathy, amyloid nephropathy, and focal segmental glomerulosclerosis. There was a significant discrepancy between the urinary protein/creatinine ratio and daily proteinuria after the 7th decade of life.Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.

DOI： 10.1007/s10157-012-0673-8

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5x10(-32) 3x10(-10)), with heterogeneity detected only at the PSMB9/TAP1 locus (I-2 = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5x10(-4)). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3x10(-128)). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

DOI： 10.1371/journal.pgen.1002765

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語  

Gastric antral vascular ectasia (GAVE) is currently recognized as an important cause of gastrointestinal bleeding. Chronic kidney disease (CKD) is associated with a high incidence of GAVE. We report 3 patients with CKD who presented with severe anemia and were diagnosed with GAVE; they were resistant to endoscopic argon plasma coagulation. However, remission of anemia and improvement in GAVE lesions were observed after the initiation of hemodialysis. The pathogenesis of GAVE remains largely unknown, but mechanical stress of the antrum could play an important role. This stress may be reduced by hemodialysis through improvement of uremia-associated gastrointestinal symptoms. Therefore, the initiation of hemodialysis might be effective for intractable GAVE in CKD patients.

DOI： 10.1159/000332832

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Arg95Stop mutation of exon 4 in complement component 9 (C9) gene is common in individuals in Japan with C9 deficiency (C9D); however, understanding of the influences of C9D on human glomerulonephritis remains elusive. METHODS: A total of 1288 patients with chronic kidney disease (CKD) were recruited from the hospitals in Niigata prefecture. They were screened for the Arg95Stop mutation of C9 gene by allele-specific PCR. RESULTS: We identified two individuals with C9D among 1,288 CKD patients, a frequency comparable to that of the general Japanese population (0.16%). Case 1 involved a 44-year-old man presenting with nephrotic proteinuria. The hemolytic activity of CH50 was low, and the concentration of C9 was not detected. Sequencing of exon 4 of the C9 gene showed the Arg95Stop mutation. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Mesangial, subendothelial and subepithelial deposits were noticed with light and electron microscopy. Immunofluorescent study showed predominant mesangial IgA deposition. Case 2 involved a 62-year-old man presenting with proteinuria and hematuria. His CH50 level was decreased. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Immune deposits were also confirmed. The percentage of C9D among patients with mesangial proliferation and duplication of GBM in this study was 5.1%. CONCLUSION: These results suggested that the lack of membrane attack complex because of an Arg95Stop mutation of the C9 gene predisposed patients to pathognomonic glomerulonephritis.

DOI： 10.1007/s10157-010-0358-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000320175

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) often have inflammation and dyslipidemia that accelerate to atherosclerosis. This study aimed to evaluate chronic inflammation and dyslipidemia in CAPD patients.Methods: We measured inflammatory markers and lipoprotein subclasses in 20 CAPD patients (12 men and 8 women. aged 59.5 +/- 99 y) and 20 gender-matched controls. Lipoproteins were separated by high-performance liquid chromatography (HPLC) using an anion-exchange columnResults. High-sensitivity C-reactive protein and scrum amyloid A protein (SAA) were higher among CAPD patients vs. controls (1.6 +/- 2 2 vs 08 +/- 1 2 mg/l. p<0.05. 11.9 +/- 128 vs 45 +/- 24 mg/l). HPLC analysis revealed that chylomici on. VLDL. and IDL cholesterol levels were higher among CAPD vs controls In contrast, HDL cholesterol was lower among CAPD patients vs controls In the subgroup analysis, SAA levels were significantly lower among patients receiving CAPD for >3 y than among controls However, IDL cholesterol was consistently higher among CAPD patients vs controlsConclusions CAPD patients have chronic inflammation and dyslipidemia IDL cholesterol is the only lipoprotein subclass that is consistently elevated regardless of CAPD duration More attention should be paid to dyslipidemia in the management of the CAPD patients. (C) 2010 Elsevier B V All rights reserved.

DOI： 10.1016/j.cca.2010.07.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We present here a male patient who had developed nephrotic syndrome 11 yr after kidney transplantation. Nephrotic syndrome suddenly occurred after severe sunburn he got in Hawaii. Such a clinical course seemed very rare in kidney transplantation, and multifactorial etiology was suspected. The histological findings of graft biopsy were intricate. On light microscopy, there were mesangial expansion and endocapillary proliferation with duplication of GBM and crescent formation. Deposits of IgM in mesangium were the most prominent finding on immunofluorescence microscopy, but IgA and C3 deposits were also detected. Electron microscopy revealed paramesangial and a few subepithelial dense deposits. Additionally, small organized deposits were found in the subepithelial space. Based on these findings, a provisional diagnosis of IgA nephropathy superimposed on chronic transplant glomerulopathy was made. However, hepatitis C virus related nephropathy could not be excluded. © 2007 Blackwell Munksgaard.

DOI： 10.1111/j.1399-0012.2007.00715.x

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1111/j.1440-1797.2006.00690.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PORTLAND PRESS LTD  

To better understand the molecular pathogenesis of OPLL (ossification of the posterior longitudinal ligament) of the spine, an ectopic bone formation disease, we performed cDNA microarray analysis on cultured ligament cells from OPLL patients. We found that TSG-6 (turnout necrosis factor a-stimulated gene-6) is down-regulated during osteoblastic differentiation. Adenovirus vector-mediated overexpression of TSG-6 inhibited osteoblastic differentiation of human mesenchymal stem cells induced by BMP (bone morphogenetic protein)-2 or OS (osteogenic differentiation medium). TSG-6 suppressed phosphorylation and nuclear accumulation of Smad 1/5 induced by BMP-2, probably by inhibiting binding of the ligand to the receptor, since interaction between TSG-6 and BMP-2 was observed in vitro. TSG-6 has two functional domains, a Link domain (a hyaluronan binding domain) and a CUB domain implicated in protein interaction. The inhibitory effect on osteoblastic differentiation was completely lost with exogenously added Link domain-truncated TSG-6, while partial inhibition was retained by the CUB domain-truncated protein. In addition, the inhibitory action of TSG-6 and the in vitro interaction of TSG-6 with BMP-2 were abolished by the addition of hyaluronan. Thus, TSG-6, identified as a clown-regulated gene during osteoblastic differentiation, suppresses osteoblastic differentiation induced by both BMP-2 and OS and is a plausible target for therapeutic intervention in OPLL.

DOI： 10.1042/BJ20060027

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet. METHODS: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene. RESULTS: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype. CONCLUSIONS: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

DOI： 10.1007/s10157-005-0375-6

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記述言語：英語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.54.988_2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Aspirin-intolerant asthma (AIA) is a subtype of bronchial asthma characterized by development of bronchoconstriction evoked by non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit the cyclooxygenase pathway, leading to enhancement of the lipoxygenase pathway. We evaluated allelic association of 370 single nucleotide polymorphisms (SNPs) of 63 candidate genes, mostly from the arachidonic acid metabolic cascade, with AIA. After two rounds of screening with 198 AIA patients, multiple SNPs in the prostaglandin E(2) receptor subtype 2 (EP2) gene were associated with AIA (P<0.05). Among the 77 SNPs identified in the EP2 gene, we selected 17 SNPs on the basis of linkage disequilibrium and allelic frequencies (minor allele frequency >0.1) for further association study. SNPs in the promoter region of the EP2 gene, uS5, uS5b, and uS7, were significantly associated with AIA (permutation P=0.039-0.001). Analysis of haplotypes constructed according to the LD pattern showed a significant association with AIA (permutation P=0.001). The most significantly associated SNP, uS5, located in the regulatory region of the EP2 gene, was in a STATs-binding consensus sequence [AIA 31.1% versus control 22.1% (permutation P=0.0016) or versus aspirin-tolerant asthma 22.2% (permutation P=0.0017)]. Although STAT1 binding was not observed in gel mobility shift assay with HeLa nuclear extract, an unidentified protein was specifically bound to the allelic sequence. In in vitro reporter assay in HCT116 cells, the site containing the uS5 allele showed reduced transcription activity. Taken together, these results suggest that uS5 allele serves as a target of a transcription repressor protein. A functional SNP of the EP2 gene associated with risk of AIA should decrease the transcription level, resulting in reduction of the PGE(2) braking mechanism of inflammation and involvement in the molecular mechanism underlying AIA.

DOI： 10.1093/hmg/ddh332

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Transforming growth factor (TGF)-beta1, a multifunctional cytokine, which regulates proliferation and differentiation of a variety of cell types, has the central role in the development and progression of renal injury in both animal models and human. Although it has been suggested that genetic variations in the TGF-beta1 gene are associated with the activity of the gene product, their clinical significance in glomerular disease is unknown. We investigated whether the polymorphisms of C-509T and T869C in TGF-beta1 account for interindividual variation in manifestations of IgA nephropathy (IgAN) using 626 Japanese subjects including 329 patients with histologically proven IgAN and 297 healthy controls with normal urinalysis. The frequencies of genotypes, alleles, and major haplotypes were similar between the patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium, and the major haplotypes were C-C and T-T, which accounted for more than 95% of the total. In patients with -509CC and in those with the 869CC, urinary protein excretion was higher than in those with other genotypes, whereas no difference in other clinical manifestations was noted. Moreover, patients with -509CC and those with 869CC genotypes presented with a significant higher score of mesangial cell proliferation than in those with other genotypes. These results suggest that TGF-beta1 gene polymorphisms are specifically associated with heavy proteinuria and mesangial cell proliferation in Japanese patients with IgAN, although they do not confer susceptibility to this disease.

DOI： 10.1111/j.1399-0039.2004.00256.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND AND PURPOSE: Inflammatory cytokines are involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to examine the role of p38 mitogen-activated protein kinase (MAPK) in the development of vasospasm and cytokine production. METHODS: We measured the expression levels of genes and proteins related to inflammation in human vascular smooth muscle cells (hVSMCs) treated with hemolysate and FR167653 (FR) (1 micromol/L), a selective p38MAPK inhibitor, for 48 hours by TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. Twenty-one dogs were assigned to 3 groups of 7 animals: control, placebo, and FR-treated (1 mg/kg/d) groups in a double-hemorrhage model. The effects were assessed through the caliber of the basilar artery, and the changes in gene expressions and the activation of p38MAPK were assessed by Western blot analysis. RESULTS: Treatment of hVSMCs with hemolysate induced significant upregulation of interleukin (IL)-1alpha, IL-1beta, and IL-8 gene and protein expressions, which was suppressed significantly with FR. The mean vessel caliber on day 7, as a percentage of that of day 0, was 49% in the placebo, and 74% in the FR group (P=0.0001). The gene expression levels of IL-1alpha, IL-1beta, and IL-8 in the arterial wall were extremely elevated in the placebo, and significantly suppressed in the FR group (P=0.0027, 0.0002, and 0.0073). p38MAPK phosphorylation was stimulated in the placebo and hemolysate in vitro, and suppressed in the FR group. CONCLUSIONS: These results suggest that p38MAPK is activated in the arterial wall after SAH, leading to the development of vasospasm, possibly through the upregulation of inflammatory cytokines.

DOI： 10.1161/01.STR.0000127425.47266.20

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：B M J PUBLISHING GROUP  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL MUNKSGAARD  

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in lipid metabolism, insulin sensitivity, atherogenesis, and immune regulation. A genetic polymorphism (C161T) at exon 6 of PPARgamma gene (PPARG) was reported to be associated with the onset of coronary artery disease. However, there has been no report of an association with renal disease. Genomic DNAs were isolated from 225 Japanese patients with histologically confirmed immunoglobulin A nephropathy (IgAN). The PPARG C161T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. The association of the polymorphism with renal prognosis in IgAN patients was analyzed using the Kaplan-Meier method and Cox proportional hazard regression model. The PPARG polymorphism was not associated with the renal survival rate. However, when patients were stratified into those either with or without hypertension at the time of diagnosis, the renal survival of the CT/TT genotypes was significantly better in those without hypertension than those with the CC genotype. We report that the PPARG C161T polymorphism is associated with the survival of IgAN patients without hypertension. The T allele of the polymorphism might have a protective effect on the progression of IgAN.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DUSTRI-VERLAG DR KARL FEISTLE  

A 41 year-old woman complained of general bone pain and polyuria. She did not have Albright hereditary osteodystrophy. Laboratory examination revealed hypokalemia, hypocalcemia, and an elevation of serum intact PTH concentration. The patient was polyuric and relatively hypercalciuric, though her glomerular filtration rate (GFR) was normal. Neither urinary Pi nor cAMP excretion was remarkably promoted by an exogenous PTH load. An iliac bone biopsy revealed osteopenia, active osteoclastic bone resorption, fibrous transformation in bone marrow tissue, and severely disturbed calcification. Although the oral administration of alfacalcidol showed no effects, 3 weeks of intermittent intravenous injection of maxacalcitol therapy decreased the serum intact PTH concentration from 597 pg/ml to 40 pg/ml, and the bone pain was greatly relieved. However, plasma Ca concentration also decreased and symptoms of tetany appeared. Pseudohypoparathyroidism type Ib was the most likely diagnosis in this patient. In conclusion, maxacalcitol therapy satisfactorily suppressed parathyroid function in a patient with secondary hyperparathyroidism without uremia. Appropriate Ca supplementation was required to perform it safely.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING INC  

BACKGROUND: Blockade of the renin-angiotensin system (RAS) is well documented to be renoprotective; however, not all patients with glomerulonephritis respond well to this therapy. The interindividual variation in response to the RAS blockade may be in part genetically determined, whereas the results have been controversial. METHODS: We investigated whether the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker on renal prognosis is modified by the angiotensinogen gene (AGT) polymorphism in immunoglobulin A nephropathy (IgAN). In total, 259 patients with histologically proven IgAN were analyzed for clinical manifestations, renal survival, and their associations with AGT A(-20)C and M235T. RESULTS: The renal prognosis of 110 patients, who received ACE inhibitors/angiotensin receptor blocker during their clinical course, was significantly better than those without ACE inhibitors/angiotensin receptor blockers despite higher blood pressures and heavier proteinuria. The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 1.0 g/day) of 3.346 (P = 0.0001), hypertension of 1.949 (P = 0.01), deteriorated renal function of 3.040 (P < 0.0001), no ACE inhibitor/angiotensin receptor blocker administration of 2.725 (P = 0.0004), and the T235 and C(-20) haplotype of 1.608 (P = 0.0322). Only in patients carrying at least one M235 and A(-20) haplotype did the administration of ACE inhibitors/angiotensin receptor blockers have no significant effect on the prognosis of renal function (Kaplan-Meier, log rank test, chi2 = 0.700; P = 0.4028), whereas it was significant in patients who had other haplotypes of AGT (chi2 = 11.805; P = 0.0006). CONCLUSION: This study provides evidence that the M235T and A(-20)C genotype of AGT can influence the therapeutic efficacy of a RAS blockade on the renal survival in IgAN.

DOI： 10.1046/j.1523-1755.2003.00187.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi2=6.062, P=0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P=0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P=0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.

DOI： 10.1161/01.HYP.0000085193.25617.78

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN.

DOI： 10.1097/01.LAB.0000080600.49276.31

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BRITISH MED JOURNAL PUBL GROUP  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

The SA gene has been shown to be much more highly expressed in the kidneys of spontaneously hypertensive rats than in the corresponding wild-type strain. Genetic polymorphism of this gene has been shown to play a role in human hypertension, although the details of this association remain controversial. We investigated the possible associations between SA gene polymorphism and both hypertension and the prognosis of renal function in patients with immunoglobulin A nephropathy (IgAN). Genomic DNA was isolated from the peripheral blood of 367 individuals, including 274 patients with histologically proven IgAN and 100 controls without any history of renal disease. The SA genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) with Pst I. The frequencies of genotypes and alleles were not different between the patients with IgAN and those without renal disease. In the group without renal disease, the SA gene polymorphism was not associated with hypertension. However, in the patients with IgAN the A1 allele frequency was significantly higher in the hypertensives than in the normotensives. The renal survival of the patients with the A2 allele tended to be better than that of those without the A2 allele. The findings thus suggest that SA gene polymorphism may be associated with the renal prognosis of IgAN through its effect on blood pressure. Further, they suggest that the sensitivity to this gene polymorphism increases in patients with renal injury.

DOI： 10.1291/hypres.25.831

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PARTHENON PUBLISHING GROUP  

Carpal-tunnel syndrome (CTS) in long-term hemodialysis patients is caused by the deposition of amyloid as well as by the local inflammatory process. The recruitment of monocytes/macrophages in the tenosynovium, promoted by chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), is thought to play an important role in CTS development. The genetic polymorphism of these chemokines has been identified and their clinical function has been partly revealed We attempted to analyze the relationship between these polymorphisms and their susceptibility to CTS. The subjects of this study were 366 patients who underwent hemodialysis. Ninety-five patients received surgery for CTS. No significant difference was observed in the genotype distributions of MCP-1 or MIP-1alpha between patients who received CTS surgery and those that did not. However, with the use of a logistic regression model, the MCP-1 GG genotype was identified as a risk factor for the development of CTS, in addition to the duration and the age of initiation of dialysis, as confirmed by a Cox proportional hazards model. In conclusion, homozygosity for G at -2518 in the MCP-1 gene might be a candidate for the genetic marker of CTS development in Japanese hemodialysis patients.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING INC  

BACKGROUND: The M235T polymorphism of the angiotensinogen gene (AGT) is associated with an increased risk of primary hypertension, which may then lead to progressive renal disease. Recent studies showed that nucleotide substitution in the 5' upstream core promoter region of AGT affects the basal transcription rate of the gene. METHODS: To evaluate the role of AGT polymorphisms in the progression of IgA nephropathy (IgAN), we analyzed the association of A(-20)C and M235T polymorphisms with renal prognosis in histologically-proven IgAN patients using the Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: The incidence of hypertension during the course was associated with T235, but not with C(-20). The renal survival rate for 137 patients with creatinine clearance (C(Cr)) of 70 mL/min or greater at the time of renal biopsy, and follow-up time of two years or more was significantly lower in the patients with C(-20) (P = 0.008). The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 2 g/day) of 28.3 (95% CI, 7.3 to 109.8; P < 0.001), hypertension at the time of renal biopsy of 4.6 (95% CI, 1.8 to 11.9; P = 0.002), and C(-20) of 3.6 (95% CI, 1.5 to 8.7; P = 0.004). CONCLUSION: This work provides evidence that the C(-20) polymorphism of AGT, a subset of T235 alleles, is associated with progression of renal dysfunction in IgAN.

DOI： 10.1046/j.1523-1755.2002.00517.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING INC  

BACKGROUND: Uteroglobin is a multifunctional protein and both its gene knockout and antisense transgenic mouse models develop the pathological and clinical features of IgA nephropathy. A genetic polymorphism in uteroglobin has been reported to be associated with progression of IgA nephropathy in a Caucasian population, but the findings remain controversial. METHODS: Genomic DNA was isolated from 595 individuals including 239 patients with IgAN, 160 patients with glomerulonephritis distinct from IgAN, and 196 healthy controls. The uteroglobin G38A genotype was determined by PCR-RFLP with Sau96I. To examine the possible association of uteroglobin gene polymorphism in the patients with and without IgAN, the uteroglobin genotype and allele frequency were compared between the two groups. In addition, associations between the polymorphism and blood pressure, proteinuria and prognosis of renal function were analyzed in the patients with IgAN to investigate the role of this gene polymorphism in the risk of progressive renal dysfunction in IgAN patients. RESULTS: The Cox proportional hazard regression model revealed that hypertension and proteinuria at the time of renal biopsy were independent risk factors for poor renal survival. Uteroglobin genotype was not significantly associated with the renal survival rate. However, in the patients with heavy proteinuria (more than 2 g/day) or in those with hypertension at the time of renal biopsy, the renal survival of patients with the GG genotype was significantly worse than the other genotypes. CONCLUSION: Uteroglobin GG genotype may be a genetic marker for rapid disease progression to end-stage renal failure, especially in the IgAN patients with heavy proteinuria or high blood pressure.

DOI： 10.1046/j.1523-1755.2002.00336.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

This study investigates the circadian blood pressure variation of non diabetic chronic hemodialysis (HD) patients on both HD and non-HD days as well as the factors affecting diurnal BP variation. Forty-nine HD patients aged 61.8+/-12.9 years who were on daytime HD for 97+/-68 months were studied. No significant difference was found in every daytime and nighttime BP between the first (HD) and the second (non-HD) day. However, the ratio nighttime/daytime BP was significantly higher on the second day. Each BP diurnal variability pattern was classified as either Dipper (D: the ratio nighttime/daytime mean BP 0.8-0.9), nondipper (0.9&lt; ND&lt;1.0), or inverted dipper (ID&gt;1.0). More than 75% of the cases were classified as ND (26 cases) or ID (11 cases). The ultrafiltration rate in D was significantly less than that in ND and ID. The difference of plasma renin activity between pre- and post-HD (dRen) was significantly higher in ID than in D and ND. The amount of dialysis (Kt/V) was found to be significantly correlated with nighttime BP fall. Ultrafiltration, dRen and KW were independent factors for the abnormal BP diurnal variability. In conclusion, the decreased nocturnal BP fall seen in non-diabetic HD patients is associated with increased extracellular fluid even in the patients without overt overhydration, whereas relatively insufficient amount of dialysis (low Kt/V) may be another possible cause. The increased dRen observed only in ID patients may reflect occult cardiovascular damage or functional disturbances in aortic and carotid baroreflexes caused by arterial structural changes.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG TOKYO  

The molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc alpha receptor (Fc alphaR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5'-untranslated region region of the Fc alphaR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and T+56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the Fc alphaR gene do not appear to be primarily involved in the susceptibility to IgAN.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders  

• We report the case of a patient who presented with disseminated tuberculosis-associated hemophagocytic syndrome (HPS). A 40-year-old man was admitted because of fatigue, fever, and renal dysfunction. Chest radiograph and computed tomography scan showed diffuse reticulonodular shadow, and Mycobacterium tuberculosis was identified. Peripheral blood counts decreased rapidly, and bone marrow aspiration revealed hemophagocytosis by macrophages. Despite antituberculous and steroid pulse therapy, multiple organ dysfunction syndrome developed. After plasma exchange and continuous hemodiafiltration were started, hypercytokinemia and vital signs improved dramatically. Although disseminated tuberculosis-associated HPS carries a poor prognosis, acute blood purification may be an effective means of treating HPS involving multiple organ dysfunction syndrome. © 2001 by the National Kidney Foundation, Inc.

DOI： 10.1053/ajkd.2001.27727

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Leukocyturia is associated with postinfectious glomerulonephritis (GN), interstitial nephritis, and renal allograft rejection. In addition, prominent infiltration of T cells and macrophages is commonly observed in the renal tissues of patients with GN, accompanied by cellular crescent formation and/or interstitial cell infiltration. Because these infiltrating T cells were thought to participate in the development of the diseases and to appear in the urinary space while functioning as effector cells in the renal inflammatory lesion, the study focused on the characterization of T cells that appeared in urine. Freshly voided urine cells were analyzed by flow cytometry to determine their phenotype and by reverse transcriptase-PCR to detect cytokine mRNA. In urine from patients with different forms of GN, including IgA nephropathy, Henoch-Schönlein purpura nephritis, and anti-neutrophil cytoplasmic antibody-associated GN, T cells appeared together with macrophages. The urine T cells were mainly CD45RA-, CD45RO+, and CD62L (L-selectin)-, which are the phenotypic features of effector T cells. In agreement with this finding, T cells infiltrating glomeruli, crescents, and tubulointerstitial lesions were also effector type. Moreover, these urine cells expressed mRNA of the T helper lymphocyte 1 cytokines, interleukin-2, and/or interferon-γ. These findings suggest that the appearance of effector T cells in urine may reflect the cellular immune reaction that occurs in the kidneys of patients with GN accompanied by active cell infiltration.

DOI： 10.1681/ASN.V12122636

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of plgR in the patients with and without IgAN. Subjects and Methods Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as Al and A2 with and without Pvu II site, respectively. Results The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was higher in IgAN than in other renal diseases (Al and A2
0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, X2=9.84, P=0.0017, Odds ratio=1.71). Moreover, the subjects with A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other renal diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (Al and A2
0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, X2=12.44, P=0.0004, Odds ratio=3.01). Conclusion This is the first demonstration of the pIgR gene polymorphisms in IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN. (Internal Medicine 40: 867-872, 2001). © 2001, The Japanese Society of Internal Medicine. All rights reserved.

DOI： 10.2169/internalmedicine.40.867

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The earliest commitment to the formation of glomeruli is recognizable in S-shaped bodies. Although cell-cell adhesion seems likely to play a crucial role in this process, how glomerular epithelial cells segregate from the other parts of the nephron is unknown. In this study, immunofluorescence microscopy and monoclonal antibodies specific for mouse R-, E-, P- and N- cadherins were used to examine which of these adhesion molecules are involved in glomerulogenesis of the mouse kidney. Weak R-cadherin staining was first found in the vesicle stage, becoming restricted to glomerular visceral epithelial cells (VEC) during the S-shaped body stage. The intensity of this staining became stronger in the capillary loop stage, whereas parietal epithelial cells (PEC) and tubular cells did not stain. In the maturing stage, VEC gradually lost their staining for R-cadherin. E-cadherin was detected in ureteric buds and the upper limb of S-shaped bodies. From the capillary loop to the maturing stage, anti-E-cadherin stained epithelial cells in all tubule segments, but no label was seen in VEC or PEC. P-cadherin was also stained in the ureteric buds and in the upper limb of S-shaped bodies. N-Cadherin was weakly stained in cells at the vesicle stage, but thereafter staining of N-cadherin was not detected at any stage of glomerular formation. Immunoelectron microscopy of differentiating VEC was performed using antibodies specific to α-catenin, which is associated with cadherin. Subsequently, immunogold particles identifying α-catenin were localized on junctions between primary processes of VEC. These findings indicate that R- cadherin is uniquely expressed in differentiating VEC, suggesting an important role in the early stages of glomerulogenesis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glomerular expression of the major rate-limiting enzymes for prostanoid synthesis, cyclooxygenase isoforms (COX-1 and COX-2) and cytosolic phospholipase A2 (cPLA2), was investigated in anti-Thy-1 nephritis in rats. Ribonuclease protection assay demonstrated minimal COX-1 mRNA expression in glomeruli of control rat kidneys and a gradual increase of expression from day 1 to day 10 after administration of monoclonal anti-rat Thy-1 antibody. On the other hand, COX-2 mRNA expression, also minimal in the normal glomeruli, was enhanced in a biphasic pattern with two peaks at 1 h and day 10. Expression of cPLA2 mRNA, which was undetectable in normal glomeruli, was induced on day 1 and increased gradually in a pattern similar to that of COX- 1 mRNA expression. Immunofluorescence microscopy, using antibodies against COX isoforms, showed that both COX-1 and COX-2 were negligible or faintly detectable in the glomeruli of control rat kidneys. In contrast, the immunofluorescence for COX-1 was intensified on days 4 and 10 along the glomerular capillary walls probably in glomerular epithelial and/or endothelial cells, whereas COX-2 staining was exclusively enhanced in the glomerular epithelial cells at 1 h and day 10 during the course of anti-Thy- 1 nephritis. These findings indicate that prostanoids generated through induction of COX-l, COX-2, and cPLA2 are implicated in the mediation of the mesangial cell injury model. In particular, the upregulation of COX-2 expression in glomerular epithelial cells in the selective mesangial cell injury model suggests an intercellular interaction between mesangial cells and glomerular epithelial cells.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aims: Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients. Methods: We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era. Results: The mean duration of HD was 6 years, the mean duration of the patients' marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery. Conclusions: The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.

DOI： 10.1159/000045086

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE INC  

To identify genes expressed predominantly in the kidney with chronic and progressive glomerulosclerosis but not in acute and transient form of glomerulonephritis, we induced progressive glomerulosclerosis in rats by applying unilateral nephrectomy prior to injection of monoclonal anti-Thy1.1 antibody (OX-7), which cause acute and transient glomerulonephritis with single injection. In rats with nephrectomy and OX-7 injection (Nx group), proteinuria increased with time and mesangial expansion accompanied with interstitial fibrosis was recognized, whereas transient proteinuria and mesangiolysis followed by mesangial hypercellularity were seen in rats with sham operation and OX-7 injection (Sham group). Four weeks after the induction of glomerulonephritis, mRNAs were isolated from kidney cortex of both groups and used for cDNA synthesis. By subtraction hybridization of cDNAs from Nx with excess amount of those from Sham, we isolated and sequenced several genes expressed specifically in the Nx group. These included genes, which contain identical sequences with serine protease inhibitors, cytokine receptors, osteopontin as well as genes with unknown function. These genes may play important roles in the process which promotes acute glomerular damage advance to chronic and progressive glomerulosclerosis.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

To identify genes expressed predominantly in the kidney with chronic and progressive glomerulosclerosis but not in acute and transient form of glomerulonephritis, we induced progressive glomerulosclerosis in rats by applying unilateral nephrectomy prior to injection of monoclonal anti-Thy1.1 antibody (OX-7), which cause acute and transient glomerulonephritis with single injection. In rats with nephrectomy and OX-7 injection (Nx group), proteinuria increased with time and mesangial expansion accompanied with interstitial fibrosis was recognized, whereas transient proteinuria and mesangiolysis followed by mesangial hypercellularity were seen in rats with sham operation and OX-7 injection (Sham group). Four weeks after the induction of glomerulonephritis, mRNAs were isolated from kidney cortex of both groups and used for cDNA synthesis. By subtraction hybridization of cDNAs from Nx with excess amount of those from Sham, we isolated and sequenced several genes expressed specifically in the Nx group. These included genes, which contain identical sequences with serine protease inhibitors, cytokine receptors, osteopontin as well as genes with unknown function. These genes may play important roles in the process which promotes acute glomerular damage advance to chronic and progressive glomerulosclerosis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Academic Press  

Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25), mRNA of IL-1β, interferon gamma INF-γ and tumor necrosis factor alpha (TNF-α) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast, IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-β1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4+ T cells, a number of neutrophils were found in the myocardium, especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-γ, which further activates macrophages in the myocardium. Consequently, TNF-α and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-β1 and one representative Th2 cytokine. IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.

DOI： 10.1006/jmcc.1996.0293

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：日本臨床社  

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その他リンク： http://search.jamas.or.jp/link/ui/2019198060

記述言語：日本語   出版者・発行元：フジメディカル出版  

近年、シークエンス技術の革新に伴い、ヒト腎疾患のゲノム解析は飛躍的に進歩した。網羅的ゲノム解析は遺伝性希少疾患の原因遺伝子同定を進めるとともに慢性腎臓病患者の遺伝子診断まで試みられている。また、遺伝性間質性腎疾患の原因遺伝子から腎疾患の表現型を大きく包括する、常染色体優性尿細管間質性腎疾患(ADTKD)の疾患概念も確立された。質量分析によるプロテオーム解析もヒト腎疾患の原因解明に寄与している。原発性膜性腎症の原因は、ウェスタンブロットで患者血清に反応するヒト糸球体蛋白質が質量分析により同定された(PLA2RおよびTHSD7A)。糸球体に細線維構造物が沈着する細線維性糸球体腎炎に対しては、腎生検標本からレーザーキャプチャマイクロディセクションで糸球体を単離し、質量分析でDNAJB9が同定された。上記はいずれも診断マーカーとしても応用されている。今後も解析技術の進歩により腎疾患の原因解明と治療への応用が期待される。(著者抄録)

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その他リンク： http://search.jamas.or.jp/link/ui/2019250267

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)メディカルドゥ  

ゲノムワイド関連解析(GWAS)をはじめとした遺伝子解析技術の急速な進歩により、腎泌尿器科領域でも様々な疾患に関与する感受性遺伝子が多数同定され、病因解明に大きく貢献している。IgA腎症では、その発症に腸管を中心とした粘膜免疫が強く関与することや様々な自己免疫疾患と感受性遺伝子を共有することが判明し、特発性膜性腎症においても疾患発症に強く寄与する分子群が同定され、慢性腎臓病に関連すると判明した感受性遺伝子座は50以上にものぼる。今後、さらに感受性遺伝子の探索と環境因子との関連について研究を進めることで、多因子疾患の発症機序の解明と新たな治療法の開発につながることが期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

DOI： 10.19020/CD.0000000349

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

IgA腎症は口蓋扁桃をはじめとする上気道粘膜上皮における細菌抗原の感作が病因として想定され,わが国を中心にIgA腎症患者に対する口蓋扁桃摘出術が広く行われているが,扁摘治療の理論的根拠については未だ確立していない.一方で,急速な進歩を続けるゲノム解析技術がIgA腎症にも応用され,病巣感染に関連する病態の解明も進められている.ゲノムワイド関連解析では外来抗原に対する粘膜免疫応答に関与する複数の疾患感受性遺伝子が同定され,さまざまな自己免疫疾患と感受性遺伝子を共有することが判明した.また,次世代シークエンサーを使用したマイクロバイオーム研究により,IgA腎症に特有の細菌叢組成の網羅的解析も可能となった.今後,扁桃病巣感染と粘膜免疫応答の関連に対する解析が進められ,IgA腎症の発症機序の解明と標準治療法の開発へ繋がることが期待される.(著者抄録)

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2018235919

記述言語：日本語   出版者・発行元：(公社)日本透析医会  

背景・目的:蛋白結合尿毒症物質(protein-bound uremic toxins;PBUTs)の血中濃度高値は種々の透析関連合併症の原因となる。我々はヘキサデキル基固定セルロースビーズ(hexadecyl-immobilized cellulose bead;HICB)のPBUTsの吸着効果について臨床的に検討した。方法:HICBを含有したカラム(リクセルS-35)を維持血液透析患者に使用した。カラム通過前後と2週間使用前後の血清インドキシル硫酸(indoxyl sulfate;IS)、インドール酢酸(indole acetic acid;IAA)、フェニル硫酸(phenyl sulfate;PhS)、そしてpクレシル硫酸(p-cresyl sulfate;PCS)濃度を質量分析により測定した。結果:リクセルS-35通過後に蛋白結合していない血中フリーIS、IAA、PhSとPCS濃度は34.4±30.0%、34.8±25.4%、28.4±18.0%と34.9±22.1%減少した。しかし、蛋白結合したPBUTsはカラム通過後に有意に減少しなかった。リクセルを2週間使用したが、血中PBUT値は有意に低下しなかった。結論:HICBsはPBUTsを部分的に吸着した。この吸着効果は臨床的に十分でなく、今後PBUTs吸着効果のより優れた血液浄化器の開発が望まれる。(著者抄録)

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記述言語：日本語   出版者・発行元：新潟急性血液浄化研究会  

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記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

次世代シークエンサーの登場・発展に伴い、サンプル内の細菌叢全体のDNAを使用して網羅的に解析する、マイクロバイオーム研究が盛んにおこなわれるようになっている。IgA腎症では口蓋扁桃などの粘膜免疫反応と発症との関連性が指摘され、治療として口蓋扁桃摘出術がおこなわれているが、理論的根拠はいまだに得られていない。今回、16SリボソームRNA解析を使用して、IgA腎症患者の口蓋扁桃の細菌叢を検討した。各細菌属の存在比率や検体間の系統組成を分析した結果、IgA腎症では小児扁桃肥大との明確な違いが観察された。一方でIgA腎症患者の口蓋扁桃のマイクロバイオームは習慣性扁桃炎患者と類似しているという結果が得られ、IgA腎症の発症には扁桃の感染病巣としての役割、さらに細菌に対する生体の反応が重要であることが考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：BioMed Central Ltd.  

Accumulation of uremic toxins induces various uremia-related complications in patients with chronic kidney disease, particularly those undergoing dialysis treatment. Direct interactions of uremic toxins with organ tissues are thought to be a major pathophysiological mechanism for disease
for example, indoxyl sulfate reacts directly with macrophages and accelerates atherosclerosis. The removal of sufficient volume of uremic toxins will prevent uremia-related complications in dialysis patients. Hemodialysis with the use of a high-flux dialysis membrane, long or frequent treatment, and increased blood/dialysate flow has improved removal of water-soluble small molecular weight uremic toxins. Middle molecular weight molecules are removed more effectively with hemodialysis using a high-flux membrane, hemodiafiltration and hemofiltration, and a direct hemoperfusion method using β2-microglobulin adsorption column, which is useful in reducing serum β2-microglobulin levels as well as improving dialysis-related amyloidosis-induced clinical symptoms. With improvements in dialysis therapies, removal of low and middle molecular weight water-soluble molecules has improved
however, conventional dialysis treatment is limited in its ability to remove protein-bound uremic toxins (PBUTs). Recent findings suggest that adsorption treatments using oral charcoal adsorbent, mixed matrix membrane hollow fiber, and additive charcoal in the dialysate, in addition to conventional dialysis treatment, may effectively remove a substantial amount of PBUTs. Further improvement of renal replacement therapy, including dialysis and additional therapeutic strategies, is needed for better clearance of small and middle molecular weight molecules and PBUTs, which will lead to improved survival and quality of life for dialysis-dependent chronic kidney disease patients.

DOI： 10.1186/s41100-016-0056-9

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本口蓋裂学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

ヒトの常在細菌叢ゲノムを解析する技術であるヒトマイクロバイオーム研究は,近年発達が著しい分野のひとつである.常在細菌叢ゲノムを網羅的に解析するこの手法は,従来,培養困難で,その存在すら知られていなかった共生細菌の存在を明らかにした.これらが宿主にとっても必要不可欠な機能を共有しており,また,常在細菌叢の異常が数々の疾患の発症と密接に関わっていることが明らかになってきている.マイクロバイオーム研究の現況を踏まえ,今後の臨床腎臓学への応用について考察する.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00974&link_issn=&doc_id=20151210100091&doc_link_id=issn%3D0022-1961%26volume%3D116%26issue%3D6%26spage%3D1214&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D116%26issue%3D6%26spage%3D1214&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：一般社団法人 日本内科学会  

DOI： 10.2169/naika.104.1930

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01159&link_issn=&doc_id=20150918170030&doc_link_id=10.2169%2Fnaika.104.1930&url=https%3A%2F%2Fdoi.org%2F10.2169%2Fnaika.104.1930&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：メディカルレビュー社  

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その他リンク： http://search.jamas.or.jp/link/ui/2015015827

記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：(株)南江堂  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00974&link_issn=&doc_id=20140611240061&doc_link_id=10.15106%2FJ00974.2014274446&url=https%3A%2F%2Fdoi.org%2F10.15106%2FJ00974.2014274446&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)中外医学社  

ヒトゲノムに続く第2のヒトゲノムとして,ヒトマイクロバイオームが注目されている.マイクロバイオームとは,そこに存在する微生物全体を指す用語である.人体にはヒトの細胞の10倍を超える数の常在細菌(約1000兆個)が存在しており,常在菌の種類や菌数,組成比は個人間で大きな多様性を示す.近年,ヒトマイクロバイオームの実態が明らかになるとともに,ヒトの健康状態との関連性が研究され始めている.ヒトが合成できない化合物の遺伝子を持つ細菌や免疫に関与する細菌などが指摘されており,マイクロバイオーム研究によって,これまでとは違った方向から人体へのアプローチができる可能性がある.本稿では,マイクロバイオーム研究の概要とともに,現在最も多く行われている腸内細菌叢研究を中心に概説し,腎臓分野における今後の展望を考察する.(著者抄録)

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

対象は平成22年10月〜23年10月に登録されダルベポエチンアルファ(DA)による治療を開始した保存器慢性腎臓病(ND)患者181例(男112例、女69例、平均年齢74.0歳)と、平成23年10月〜24年4月に登録されエポエチンベータペゴル(C.E.R.A.)による治療を開始したND患者140例(男86例、女54例、平均年齢73.8歳)。いずれもヘモグロビン(Hb)値(g/dL)は、ベースラインの9.6〜9.7から投与開始2ヵ月後には10.3〜10.5へ上昇し、以後観察期間を通して11.0以上13.0未満の達成割合は40〜50%で推移した。一方、赤血球造血刺激因子製剤(ESA)未投与患者におけるHb値上昇速度はDAが0.137/週、C.E.R.A.は0.063/週と2倍の違いを認め、前者がより短い期間でHb値を目標範囲に到達し得ることが示唆された。観察期間中、血圧の変動は来たさず安全性が示された。

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記述言語：日本語   出版者・発行元：(株)南江堂  

膜性増殖性糸球体腎炎(MPGN)は蛍光抗体所見により,免疫複合体を介したMPGN(IC-MPGN)と補体副経路を介したMPGN(AP-MPGN)に分類される.IC-MPGNの多くは基礎疾患を有し,感染症,自己免疫疾患,血液疾患が重要である.AP-MPGNでは補体制御分子の遺伝子変異や自己抗体が関与する.IC-MPGNの治療は,基礎疾患に対する治療が優先される.基礎疾患が不明の特発性については,ネフローゼ症候群や高度の組織障害を示す症例については,副腎皮質ステロイドや免疫抑制薬の併用が試みられる.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00974&link_issn=&doc_id=20130926230011&doc_link_id=issn%3D0022-1961%26volume%3D112%26issue%3D4%26spage%3D699&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D112%26issue%3D4%26spage%3D699&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2014076243

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

DOI： 10.4009/jsdt.46.501

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01159&link_issn=&doc_id=20130524160010&doc_link_id=10031185292&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10031185292&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)中外医学社  

次世代シークエンサーの登場により,短時間で大量の配列情報を解析することが可能な時代が到来した.シークエンサー機器の開発速度は著しく,いわゆる「1000ドルゲノム」が現実となりつつある.次世代シークエンサーは様々な研究分野に影響を与えており,疾患遺伝子研究においてはエクソーム解析が精力的に行われている.エクソーム解析では,得られた配列データから変異リストを作成し,主にフィルタリング法を用いて候補遺伝子を絞り込む.腎臓病研究においても遺伝性希少疾患を中心にエクソーム解析は応用され,原因遺伝子が同定されている.このようなパーソナルゲノム研究は近い将来,診療へ導入されることが推測されるが,個人のゲノム情報が適切に保護される基盤整備が必要である.(著者抄録)

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2013193659

記述言語：日本語   出版者・発行元：新潟医学会  

高血圧は心血管病の最大の危険因子であり, 家庭血圧を用いた厳格な血圧コントロールが重要である. 近年は内臓肥満, メタボリックシンドロームや糖尿病, 慢性腎臓病などの疾患が増加し, 高血圧の病態との関連が注目されている. 超高齢化社会を迎え, 高齢者高血圧の降圧療法も重要な課題であり, 高血圧診療の指針としてJSH2009が活用されている.

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その他リンク： http://hdl.handle.net/10191/35438

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)東京医学社  

新規導入患者の年次比較、腹膜透析(PD)継続患者の集計、2009年初回登録患者の1年予後について解析した。導入期の総Kt/Vはガイドラインで示される総Kt/V最低値1.7以上を示した。導入期に総Kt/V1.7以上を満たす症例(達成率)はそれぞれ65.6%、73.3%と経時的に上昇した。継続患者では総Kt/Vの平均値1.88、達成率60.7%であった。男性において総Kt/V≧1.7達成率が49.5%であったのに対し女性では87.8%と高率であった。尿量100mL/日をカットオフ値とすると、PD継続期間と血中β2MG値の2項目に有意差がみられた。継続患者の1日尿量に関して、残腎KがVのみならず総Kt/Vと有意な正相関、PD Kt/Vとは負の相関を認めた。原疾患別に糖尿病性腎症群では、その他の腎症群に比較して1年後の生存率が有意に低下した。

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その他リンク： http://search.jamas.or.jp/link/ui/2013095414

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

DOI： 10.4009/jsdt.45.651

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

高P血症合併PD患者に炭酸ランタン(LaC)を投与し、消化器症状関連QOLの変化を検討した。高P血症合併PD患者11例を対象とした。原疾患は慢性糸球体腎炎8例、腎硬化症3例であった。血清P濃度は8週間後から有意に低下し、12週間後には5例の血清P濃度が管理目標値に到達した。血清補正Ca濃度およびintact-PTHには有意な変化は認めなかった。12週間後のLaC投与量は1500±671mg/日であった。CaCO3、セベラマー塩酸塩および活性型ビタミンD製剤の試験期間中の投与量の変更はなかった。GSRS全体スコアおよびすべての下位尺度に有意な変化は認めなかった。1例において、腹痛の副作用を認めたが、LaC投与中止および下剤の投与により軽快した。LaCはPD患者の高P血症治療の新たな選択肢として有用と考えられた。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

腹膜透析(PD)合同レジストリーとベースライン解析を実施した。多施設合同レジストリーと前向きコホート研究を開始し、初年度は4施設から128例を登録した。導入原疾患では、糖尿病性腎症は31.3%で第2位であった。慢性糸球体腎炎が44.5%で第1位、腎硬化症は14.1%で第3位であった。経過年数とともに残腎Kt/Vは有意に低下し、腹膜Kt/Vは増加し、総Kt/Vは一定であった。糖尿病(DM)群で残腎Kt/Vの低下および腹膜Kt/Vの増加が顕著な傾向を認めた。残腎機能に関して、尿量100mL/日以上が88.3%を占めた。尿量と残腎Kt/Vは有意な正相関、腹膜Kt/Vは負相関を認め、DMの有無にかかわらず同様の傾向を認めた。腹膜透過性が高い群ほどDMの割合が高く、イコデキストリン使用頻度が高かった。DM群で男性が多く、腹膜透過性の亢進、尿量減少、イコデキストリン・高張液処方率が高値であった。

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2011326232

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：日本メディス(株)  

腹膜透析患者18例(男12例・女6例・平均67.2歳)を対象に、エポエチンベータ製剤とダルベポエチンアルファ製剤を用いて皮下投与時の疼痛に関し一重盲検クロスオーバー比較試験を行った。その結果、投与終了直後のVisual Analog Scale(100mm)平均値はエポエチンベータ製剤が40.7mm、ダルベポエチンアルファ製剤が65.4mm、投与終了1分後はそれぞれ7.4mm、18.8mmで、エポエチンベータ製剤の方が疼痛程度は有意に低かった。Wong-Baker Face Pain Rating Scale(6段階評価)では、投与終了直後でエポエチンベータ製剤が推定平均1.6、ダルベポエチンアルファ製剤が2.7で、エポエチンベータ製剤の方が疼痛程度は有意に低値であった。スコア出現頻度はエポエチンベータ製剤1.5、ダルベポエチンアルファ製剤3.5が最も多く、中央値はそれぞれ1.5、2.5で、Wilcoxon符号付順位和検定ではエポエチンベータ製剤で強い痛みを感じた患者が有意に少なかった。

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記述言語：日本語   出版者・発行元：(株)南江堂  

・CKDの進行や治療効果には基礎疾患が同じでも個人差が認められ、患者個人の遺伝背景によるところが大きい。・近年、ゲノム解析技術の著しい進歩により患者個人が有する遺伝情報を網羅的に解析することが可能となり、あらかじめ治療薬の効果や投薬量、副作用の有無を推測することが一部の薬剤では可能となりつつある。また、腎疾患の発症や進行を予測するバイオマーカーの探索も進められている。・将来、これらの情報が適切に医療の現場に提供され、患者個人に適した治療や腎疾患の予防・早期発見・早期治療につながるオーダーメイド医療の実現が望まれる。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00974&link_issn=&doc_id=20110128230019&doc_link_id=issn%3D0022-1961%26volume%3D107%26issue%3D2%26spage%3D295&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D107%26issue%3D2%26spage%3D295&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(株)中外医学社  

ヒトゲノムの解読と HapMapプロジェクトにより, Single Nucleotide Polymorphism (SNP)データベースが整備され,全ゲノム関連解析 Genome-Wide Association Study(GWAS)が可能になった.GWASにより多くの疾患のリスクアレル (common variant)が明らかになり,腎臓領域でも腎機能やCKD,糖尿病性腎症,IgA腎症と関連するSNPsが報告されている.ゲノムシークエンス技術の著しい進歩とともに, copy number variationやrare variantの関与も明らかとなり,複合疾患の遺伝背景の解明が期待される.(著者抄録)

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記述言語：日本語   出版者・発行元：(株)日本医学館  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

55歳男。慢性腎不全が進行して51歳時に腹膜透析導入され、以後CAPDを継続していた。今回、便潜血陽性を指摘され、大腸内視鏡検査にて上行結腸肝彎曲よりに0-I sp型の腫瘍性病変を認め、生検で大腸癌、深達度smと診断された。入院時の諸検査より上行結腸癌[A]cSMcN0cH0cM0 cStage Iと術前診断し、腹腔鏡下右半結腸切除術D3郭清を施行した。腫瘍は漿膜面に引きつれを認め、術後診断はMPsN0sH0sP0sM0 sStage Iであった。なお、手術に際しては第3病日より血液透析を週3回併用し、CAPDは手術日早朝に排液した。術後は2日目よりHD週3回を継続し、約2週間でCAPD再開して15日目に退院となった。術後85日目に腹膜機能検査を行ったが、術前と比べ明らかな低下は認めなかった。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

2005年に全国腎臓病協議会が実施した透析患者へのアンケート調査によると、PD選択者のうち70%以上がHDについて何らかの説明を受けていたが、HD選択者のうちPDについて説明を受けていたのは40%以下であった。これは療法説明において内容の偏り・情報不足があることを示唆している。当院では2004年3月から一部の患者に対して看護師による療法説明を開始した。また、腎代替療法導入時のさらなる看護介入の必要性を感じ、2009年3月に看護師による「腎疾患指導外来」を開設した。今回、開設後約半年を経過し、現在の活動状況について報告した。また、「腎疾患指導外来」受診後の患者(腎代替療法導入前)に対してKDQOL-SFによる調査を行い、本外来受診者の特徴と、療法選択時に求められる看護について検討したので併せて報告した。KDQOL-SF調査の結果、本外来受診者の特徴として、身体的・社会的機能は保たれているが、精神面の健康度はやや低く、障害受容過程の段階にあることが示唆された。療法選択時に求められる看護とは、まず患者の思いや悩みの内容をじっくり聞き、患者の感情を受け止めつつ情報提供や指導を行い、適応を促すことであると考えられた。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

腹膜透析(PD)患者の貧血治療において従来用いられていたエポエチンアルファ/ベータ(Epo)に比べ、遺伝子組換えヒトエリスロポエチン製剤であるダルベポエチンアルファ(DA)は約3倍の半減期を有するため投与間隔を長くできる特徴がある。そこで今回、EpoからDAに切り替えることで貧血が改善できるかについて検討した。対象はDA切り替え前の平均Hb濃度11g/dl未満のPD患者22例(男性14例、女性8例、平均年齢64.6±11.4歳)で、DAに切り替え後3ヵ月経過時点でHb濃度11g/dl以上となった達成群(A群)と11g/dl未満の非達成群(NA群)の2群間で比較した。その結果、EpoからDAへの切り替えにより全例で貧血は改善したが、切り替え後3ヵ月時点での比較では、A群ではNA群と比較して有意に貧血の程度が軽く、血清尿酸値・血清リン値が低く、尿素クリアランスにおいても透析液のみのweekly kt/vが有意に高かった。以上より、腹膜透析において透析効率の良い群においてはDAによる貧血改善効果が高いことが推察された。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

高齢透析患者を対象に心血管系合併症(CVD)における腹膜透析(PD)と血液透析(HD)の影響について多施設共同研究で検討した。対象は55歳以上、3ヵ月以上にわたり透析治療を継続している症例で、2009年11月時点でPDは53例(男性36例、女性17例、平均年齢68.1±7.9歳)、HDは50例(男性29例、女性21例、66.9±8.0歳)が登録された。その結果、1)70歳以上はPD43.4%・HD46.0%、透析期間はPD22.8±12.5ヵ月・HD68.2±65.2ヵ月、糖尿病はPD37.8%・HD32.0%、高血圧PD90.6%・HD82.0%、CVDはPD28.3%・HD18.0%であった。2)CVD関連血液マーカーではNT-proBNPはPDよりHDが有意に高値であり、Fetuin-AはHDが有意に低値であった。3)透析期間と血液マーカーの間にはPDでは有意な相関関係は認められなかったが、HDでは Fetuin-Aと透析期間に有意な負の相関がみられた。4)CVDと血液マーカーとの関連では、HDでCVDを有する症例でNT-proBNP が高値を示す傾向、PDではCVDを有する症例でFetuin-Aが有意に低値を示すことが明らかとなった。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

PD患者宅と病院にテレビ電話付き情報端末を設置してインターネット回線を通した診療を行うことが可能であるか検討した。音声の条件は、顔をみながらハンズフリーでの会話ができること、映像の条件は、診療に耐えうる品質の映像が得られ、瞬時に画面の切り替えができることをゴールに設定して実証実験を行った。結果、音声・映像とも目標は概ね達成された。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

CiNii Article

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その他リンク： http://search.jamas.or.jp/link/ui/2011176734

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

腎糸球体病変は全身性疾患に伴うことが非常に多く、なかでも肝炎ウイルスに合併する腎症は慢性肝炎をはじめとする肝障害とともに総合的に治療する必要がある。近年、インターフェロン(IFN)や抗ウイルス薬の進歩は著しく、肝炎ウイルス関連腎症の治療にも応用されている。C型肝炎ウイルス(HCV)感染症では混合型クリオグロブリン血症・膜性増殖性糸球体腎炎を伴いやすく、腎機能に応じたインターフェロン・リバビリンによる治療が推奨される。B型肝炎ウイルス(HBV)感染症は慢性腎症・膜性増殖性糸球体腎炎と関連があり、若年者ではインターフェロン、中年以降ではエンテカビルによる治療が推奨される。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J00060&link_issn=&doc_id=20100614090010&doc_link_id=%2Faa7ayuma%2F2010%2F023311%2F011%2F1096-1098%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2010%2F023311%2F011%2F1096-1098%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J02822&link_issn=&doc_id=20100616470007&doc_link_id=10.4009%2Fjsdt.43.426&url=https%3A%2F%2Fdoi.org%2F10.4009%2Fjsdt.43.426&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：東京医学社  

CiNii Article

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記述言語：日本語   出版者・発行元：(株)日本医学館  

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記述言語：日本語   出版者・発行元：(NPO)生物試料分析科学会  

透析患者における血清脂質とアポ蛋白、炎症マーカの特徴を明らかにするために、透析患者と健常ボランティアにおいてこれらを測定し、両者を比較検討した。透析患者17例(透析群)と、健常者17例(正常群)を対象とした。透析群では、正常群に比べTCが25%、LDL-Cが28%低く、これに対応してアポBも18%低かった。TG、アポCIII、アポEは両群でほぼ同じだったが、アポCIIのみ透析群で31%低下した。HDL-Cは透析群で22%低く、その主要成分であるPL、アポAI、アポAIIも有意な低下を示した。LCAT活性は、透析群で32%低かった。透析群では、アポB/AI比が高い傾向があり、アポCIII/アポCII比は正常群より約1.7倍と著明に上昇した。炎症マーカは、透析群ではhs-CRPが正常群の約4倍、SAAは約2倍に上昇した。

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)日本医学館  

近年、腎移植医療は著しく進歩しているが、一方で移植腎機能を喪失し、透析療法を再開する症例も増加している。最近の大規模な疫学研究から、腎移植後のPDは新規に導入するPDとほぼ同様の生命予後が得られるとする報告が多い。免疫抑制療法は、残存グラフト機能を良好に維持するために必要であるが、腹膜炎などの感染症のリスクも高まり、生命予後からみた適切な減量プロトコールの確立が望まれる。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)東京医学社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)東京医学社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(公社)全日本鍼灸学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2009143472

記述言語：日本語   出版者・発行元：(株)東京医学社  

外因性腹膜透析(PD)関連腹膜炎との鑑別に苦慮した、PDの経渦中に虫垂穿孔による急性腹症を発症し、虫垂切除、PDカテーテル抜去を施行した事例(65歳・男性)について報告した。PD患者において、消化管穿孔が原因の腹膜炎は外因性腹膜炎と比較して重症かつ予後不良であるため、外科的治療など速やかな対応が必要であると考えた。

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)東京医学社  

腹膜透析症例における動脈硬化の危険因子を明らかにすることを目的に、当院で腹膜透析を行っている32症例(糖尿病(DM)9例、非DM23例。平均腹膜透析期間:20.1±15.9ヵ月)を対象に、血管の硬さを示すCAVI(Cardio-Ankle Vascular Index)と下肢動脈閉塞の指標であるABI(Ankle Brachial Index)を測定し、臨床背景因子との関連を検討した。その結果、DM症例は非DM症例に比べて有意にCAVIが高値であり、非DM症例では年齢に加えて低HDL-C血症が危険因子であることが示唆された。

CiNii Article

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記述言語：日本語   出版者・発行元：(株)東京医学社  

抗凝固療法を受けている患者で腹膜透析カテーテル出口部作製術後に上腸間膜動脈閉塞症をきたした症例を経験した。そこで、抗凝固療法を受けている患者に対する周術期の留意点について、胸部疾患手術や内視鏡検査の際に用いられているガイドラインを参考に検討した。結果、抗凝固療法を受けている患者であっても術前にPT-INRを適正な範囲にコントロールしておけば安全に腹膜透析カテーテル留置術を行うことができ、そうすることで周術期のワーファリン休薬による過凝固など予測の難しい合併症を回避できると考えられた。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

腹膜透析(PD)における二次性副甲状腺機能亢進症(SHPT)の増悪と透析液カルシウム濃度の関連を検討することを目的に、当院に通院している透析期間が6ヵ月以上の維持PD患者19名を対象に、透析液カルシウム濃度が3.5mEq/L(高カルシウム透析液)使用群と2.5mEq/L(低カルシウム透析液)使用群に分け、SHPTのマーカーである血清intact-PTH(iPTH)などを比較、検討した。その結果、低カルシウム透析液から高カルシウム透析液へ変更した5名においてiPTHが減少する傾向がみられたことから、透析液カルシウム濃度を上げることがSHPTの進行に対して抑制的に作用することが考えられた。

CiNii Article

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   出版者・発行元：新潟大学  

Endothelin 1 (ET-1) is a potent vasoconstrictor that plays an important role in the progression of renal injury. IgA nephropathy (IgAN), the most prevalent form of primary glomerulonephritis, is one of the major causes of end stage renal disease (ESRD) and the susceptibility to progressive renal dysfunction in this disease may be determined by genetic variations. In the present study, we investigated 308 patients with biopsy-proven IgAN for possible associations between ET-1 K198N polymorphism and clinical and histopathological manifestations. At the time of biopsy, the ET-1 198KK genotype was significantly associated with a higher incidence of hypertension and lower renal function, and the renal survival of patients with the ET-1 198KK genotype was significantly worse than those with other genotypes. Moreover, with respect to the histopathological characteristics of renal biopsy findings, the 198KK genotype was significantly associated with higher scores of global sclerosis, interstitial fibrosis, and arteriosclerosis of large arteries than other genotypes, whereas no difference was observed in other histological parameters including mesangial cell proliferation, mesangial matrix increase, the adhesion of glomerular tufts to Bowman's capsule, and crescent formation. The results of the present study indicate that the K198N polymorphism can be a marker for severe renal vascular injury and poor renal survival in patients with IgAN.

CiNii Article

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その他リンク： http://search.jamas.or.jp/link/ui/2008231311

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

Incompleteness of O-glycosylation in the IgA1 hinge has been implicated as a central mechanism in the development of IgA nephropathy. Although underglycosylation was reported to be an acquired abnormality, genes for enzymes of O-glycosylation, such as C1GALT1, may be responsible for susceptibility to IgA nephropathy.

DOI： 10.1038/sj.ki.5002139

Web of Science

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記述言語：日本語   出版者・発行元：(公財)日本腎臓財団  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J00990&link_issn=&doc_id=20050315230010&doc_link_id=%2Fdg3nigta%2F2004%2F011812%2F011%2F0713-0713%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2004%2F011812%2F011%2F0713-0713%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

腎糸球体メサンギウム領域への免疫グロブリンA(IgA)沈着を伴う増殖性腎炎を特徴とするIgA腎症は,最も頻度の高い原発性糸球体腎炎であり,慢性腎不全の主要な原疾患でもある.本症におけるIgA沈着機序と腎機能低下速度の個人差の機序は不明であるが,遺伝的な背景が,本症の発症と進行の両者に関与する可能性が,近年指摘されてきた.この遺伝的背景を明らかにできれば,IgA腎症の病態と進行機序をより詳細に理解することが可能となる.最近の著者らによる臨床分子遺伝学的な研究を紹介した

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J00990&link_issn=&doc_id=20040519030001&doc_link_id=%2Fdg3nigta%2F2004%2F011803%2F001%2F0149-0153%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2004%2F011803%2F001%2F0149-0153%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：英語   出版者・発行元：BLACKWELL PUBLISHING INC  

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記述言語：日本語   出版者・発行元：(株)現代医療社  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J00990&link_issn=&doc_id=20030220040016&doc_link_id=%2Fdg3nigta%2F2002%2F011611%2F016%2F0571-0571%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2002%2F011611%2F016%2F0571-0571%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J00990&link_issn=&doc_id=20020912150003&doc_link_id=%2Fdg3nigta%2F2002%2F011605%2F004%2F0201-0205%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2002%2F011605%2F004%2F0201-0205%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：新潟大学  

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その他リンク： http://search.jamas.or.jp/link/ui/2003021483

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2002172628

記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2002197472

記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

Sprague-Dawleyラットに片腎摘出,または対照として疑似手術を行い,1時間後にマウス抗ラットThy1.1モノクローナル抗体(OX-7)を静注し,それぞれをNx群,Sham群とした.尿蛋白は,Sham群では1週に一過性に尿蛋白量が増加,3週で正常に復した.Nx群でも1週にピークを示し,3週で低下するが,その後6ヵ月まで進行性に増加した.1ヵ月目の光顕像では両群とも明らかな差はないが,6ヵ月目のSham群でメサンギウム基質の増加(1ヵ月)が減少,ほぼ正常に回復したが,Nx群ではメサンギウム基質は更に増加,一部に完全に硬化した糸球体も見られた.1ヵ月の時点の両群の腎皮質における発現mRNAをcDNA subtraction法を用いて解析,発現量に差のある遺伝子を検出,クローニングして塩基配列を決定した.得られた17クローンのうち,3,7,9,12,15のクローンは既知の塩基配列ではなく,クローン14.4はosteopontinと同一の塩基配列であった

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC NEPHROLOGY  

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記述言語：英語   出版者・発行元：AMER ASSOC IMMUNOLOGISTS  

CD8-positive lymphocytes (CD8(+) lym) and ICAM-1/LFA-1 interaction have been implicated in the glomerular accumulation of monocytes/macrophages (Mo/M0) and crescent formation in antiglomerular basement membrane (anti-GBM) glomerulonephritis of WKY rats. In the present study, the role of CD8(+) lym in the expression of ICAM-1 and inflammatory cytokines as well as in the accumulation of Mo/M0 in the glomeruli was examined by RNase protection assay and immunofluorescence microscopy. ICAM-1 expression was apparent at 1 h and markedly enhanced at day 3 in glomeruli after an anti-GBM Ab injection in parallel with glomerular accumulation of Mo/M0. Expression of mRNA for IL-1 beta, TNF-alpha, and IFN-gamma, known to enhance ICAM-1 expression, and MIP-1 alpha, MIP-1 beta, and MCP-1, known to activate leukocyte integrins or to act as chemokines, were also induced in the glomeruli at a mRNA level in a profile similar to that of ICAM-1 expression. By depleting the CD8(+) lym in the circulation, the increased glomerular expression of ICAM-1 and the cytokines, except IL-1 beta, and the Mo/M0 accumulation were suppressed, indicating a crucial role of CD8(+) lym in the accumulation of Mo/M0 through stimulation of ICAM-1 and induction of cytokines.

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：社団法人 日本呼吸器学会  

43歳女性. 麻酔導入薬の使用時に発見された肺胞低換気の精査目的で当科に入院. 神経学的および呼吸生理学的検査により中枢性肺胞低換気症候群と診断されたが, MRI, 血管造影で両側椎骨動脈の異常拡張, 蛇行による延髄腹側の圧迫を認め, 責任病変の可能性が疑われた. 夜間の人工呼吸管理により肺胞低換気は改善した. 在宅人工呼吸を導入し, 日中の生活に異常なく, 通院中である.

DOI： 10.11389/jjrs1963.34.1003

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記述言語：英語   出版者・発行元：AMER SOC INVESTIGATIVE PATHOLOGY, INC  

To elucidate a possible involvement of nitric oxide in the development of a mesangial proliferative glomerulonephritis induced by anti-Thy-1 antibody administration, glomerulnr expression of three isoforms of NO synthase (NOS), inducible NOS (iNOS), brain NOS, and endothelial NOS, was examined at both mRNA and protein levels by ribonuclease protection assay and immunofluorescence microscopy. Light microscopy showed an accumulation of polymorphonuclear leukocytes at 1 hour, lysis of mesangial cells at 1 day, a mesangial proliferative lesion at 4 to 10 days, and minimal residual glomerular lesions by 28 days. Ribonuclease protection assay showed that the glomerulnr expression of iNOS mRNA peaked at 1 hour and decreased thereafter. No substantial expression of iNOS mRNA was observed in normal glomeruli or in the nephritic glomeruli obtained at different time points (1, 4, 10, or 28 days). By immunofluorescence microscopy with a specific monoclonal antibody, an intense reaction for iNOS was demonstrated in a few cells in the glomeruli at 1 hour. Most of the iNOS-positive cells were identified as polymorphonuclear leukocytes. iNOS-positive cells were found less frequently in the glomeruli on days 1 and 4, Endothelial NOS mRNA tuns constitutively expressed in normal glomeruli and increased biphasically with two peaks at 1 hour and at 4 days or later; however, the peak expression was much less than that of iNOS mRNA at 1 hour. Expression of brain NOS mRNA was not detectable in either no,rmal or nephritic glomeruli. These results show, that iNOS is predominantly expressed in poly,morphonuclear leukocytes accumulating at 1 hour in the glomeruli of anti-Thy-1 glomerulonephritis and suggest an involvement of NO in the initiation of the disease.

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：一般社団法人 日本心身医学会