Language：English   Publishing type：Research paper (scientific journal)  

Several studies have reported an association between sarcopenia and depression. Their results, however, are inconsistent, partly due to small sample sizes and lack of consideration of important confounders. The present study aimed to cross-sectionally examine this association in community-dwelling people in Japan. This study used baseline data from the Yuzawa cohort study (age ≥ 40 years), with the final analysis population comprising 2,466 participants. A self-administered questionnaire was used to elicit information related to sarcopenia, depressive symptoms, demographic characteristics, anthropometrics, disease history, and lifestyles. Sarcopenia was diagnosed using SARC-F, a validated questionnaire including components of Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls. Depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). For depressive symptoms, prevalence ratios (PRs) were calculated, and odds ratio (ORs) were obtained using simple and multiple logistic regression analyses. Mean age of participants was 61.7 years (standard deviation = 11.8), and 10.5% and 34.7% had sarcopenia and depressive symptoms, respectively. Sarcopenic individuals had a significantly higher PR (2.00), unadjusted OR (3.67), and adjusted OR (4.96) compared to non-sarcopenic individuals, with an estimated adjusted PR of 2.7. There was a significant dose-dependent association between SARC-F scores and depressive symptoms in sarcopenic individuals (adjusted P for trend = 0.0028). In conclusion, sarcopenia and depressive symptoms were robustly associated in community-dwelling, middle-aged and older people in Japan. However, the direction of this association is unclear, and a future cohort study will be needed to determine causality.

DOI： 10.1620/tjem.2022.J024

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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BACKGROUND: Although metabolic syndrome traits are risk factors for chronic kidney disease, few studies have examined their association with urinary biomarkers. METHODS: Urinary biomarkers, including A-megalin, C-megalin, podocalyxin, albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase, were cross-sectionally assessed in 347 individuals (52.7% men) with a urine albumin-to-creatinine ratio (ACR)  < 300 mg/g in a health checkup. Metabolic syndrome traits were adopted from the National Cholesterol Education Program (third revision) of the Adult Treatment Panel criteria modified for Asians. RESULTS: Participants had a mean body mass index, estimated glomerular filtration rate (eGFR), and median ACR of 23.0 kg/m2, 74.8 mL/min/1.73 m2, and 7.5 mg/g, respectively. In age- and sex-adjusted logistic regression analysis, A-megalin and albumin were significantly associated with the clustering number of metabolic syndrome traits (3 or more). After further adjustment with eGFR, higher quartiles of A-megalin and albumin were each independently associated with the clustering number of metabolic syndrome traits (adjusted odds ratio for A-megalin: 1.30 per quartile, 95% CI 1.03-1.64; albumin: 1.42 per quartile, 95% CI 1.12-1.79). CONCLUSIONS: Both urinary A-megalin and albumin are associated with the clustering number of metabolic syndrome traits. Further research on urinary A-megalin is warranted to examine its role as a potential marker of kidney damage from metabolic risk factors.

DOI： 10.1186/s13098-021-00779-5

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Physical activity is associated with subjective well-being. In rural communities, however, physical activity may be affected by environmental factors (e.g., nature and socioecological factors). We examined the association of two physical activities in rural life (farming activity and snow removal) with subjective well-being in terms of happiness and <italic>ikigai</italic> (a Japanese word meaning purpose in life). In this cross-sectional study, we analysed data collected from community-dwelling adults aged ≥ 40 years in the 2012–2014 survey of the Uonuma cohort study, Niigata, Japan. Happiness (<italic>n</italic> = 31,848) and <italic>ikigai</italic> (<italic>n</italic> = 31,785) were evaluated with respect to farming activity from May through November and snow removal from December through April by using an ordinal logistic regression model with adjustments for potential confounders. The analyses were conducted in 2019. Among the participants who reported some farming or snow-removal time, median farming and snow-removal time (minutes per day) was 90.0 and 64.3 for men and 85.7 and 51.4 for women, respectively. Ordinal logistic regression analysis showed that longer time farming was associated with greater happiness and <italic>ikigai</italic> in men (adjusted odds ratio for first vs. fourth quartile: happiness = 1.17, 95% confidence interval [CI] = 1.01, 1.35; <italic>ikigai</italic> = 1.29, 95% CI = 1.10, 1.50), and also in women (adjusted odds ratio for first vs. fourth quartile: happiness = 1.17, 95% CI = 1.001, 1.36; <italic>ikigai</italic> = 1.42, 95% CI = 1.20, 1.67). More snow-removal time was inversely associated with happiness and with <italic>ikigai</italic> in women only (adjusted odds ratio for first vs. fourth quartile: happiness = 0.75, 95% CI = 0.67, 0.85; <italic>ikigai</italic> = 0.78, 95% CI = 0.69, 0.88). Our findings showed that physical activity in rural life was associated with happiness and with <italic>ikigai</italic>, and gender differences were observed in their associations with more snow-removal time. These results may be useful in helping to identify people in rural communities who are vulnerable in terms of psychological well-being.

DOI： 10.1057/s41599-021-00723-y

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Other Link： http://www.nature.com/articles/s41599-021-00723-y

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BACKGROUND: Income inequality has dramatically increased worldwide, and there is a need to re-evaluate the association between socio-economic status (SES) and depression. Relative contributions of household income and education to depression, as well as their interactions, have not been fully evaluated. This study aimed to examine the association between SES and depressive symptoms in Japanese adults, focusing on interactions between education and household income levels. METHODS: This cross-sectional study used data from baseline surveys of two cohort studies. Participants were 38,499 community-dwelling people aged 40-74 years who participated in baseline surveys of the Murakami cohort study (2011-2012) and Uonuma cohort study (2012-2015) conducted in Niigata Prefecture, Japan. Information regarding marital status, education level, household income, occupation, activities of daily living (ADL), and history of cancer, myocardial infarction, stroke, and diabetes was obtained using a self-administered questionnaire. Depressive symptoms were examined using the Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression analysis was used to obtain odds ratios (ORs). Covariates included age, sex, marital status, education, household income, occupation, ADL, and disease history. RESULTS: Individuals with higher education levels had lower ORs (adjusted P for trend = 0.0007) for depressive symptoms, independently of household income level. The OR of the university-or-higher group was significantly lower than that of the junior high school group (adjusted OR = 0.79). Individuals with lower household income levels had higher ORs (adjusted P for trend< 0.0001) for depressive symptoms, independently of education level. The type of occupation was not associated with depressive symptoms. In subgroup analyses according to household income level, individuals with higher education levels had significantly lower ORs in the lowest- and lower-income groups (adjusted P for trend = 0.0275 and 0.0123, respectively), but not in higher- and highest-income groups (0.5214 and 0.0915, respectively). CONCLUSIONS: Both education and household income levels are independently associated with the prevalence of depressive symptoms, with household income levels showing a more robust association with depressive symptoms than education levels. This suggests that a high household income level may offset the risk of depressive symptoms from having a low education level.

DOI： 10.1186/s12889-021-12168-8

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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OBJECTIVE: Understanding the long-term prognosis of preeclampsia (PE) is important. Proteinuria and poor renal function persist in some PE patients, but the relationship between their histopathological findings of kidney and renal prognosis is unknown. Our objective was to clarify the relationship between clinicopathological features and renal prognosis in PE patients. STUDY DESIGN: Retrospective observational study. MAIN OUTCOME MEASURES: Seventy patients who had been referred to the Niigata University Hospital between 1977 and 2014 and were diagnosed with PE were classified into unimproved and improved groups. The unimproved group included patients whose serum creatinine level had doubled and/or whose proteinuria had persisted until the end of observation, which included three patients with end-stage kidney disease (ESKD). The improved group included patients whose serum creatinine level did not double and whose proteinuria had disappeared until the last observation. We examined and compared these patients' characteristics, clinical and laboratory findings, and renal histopathological findings from percutaneous kidney biopsies. RESULTS: There were no significant differences in the clinical backgrounds and clinical findings between the two groups during pregnancy. However, light microscopy findings of their kidney biopsies were able to identify significantly more severe duplications of the capillary loop, interstitial cell infiltration, and interstitial fibrosis in the unimproved group. CONCLUSIONS: Histopathological examination of the kidney may be a valid method for predicting the long-term prognosis of renal function and for histological a risk assessment of poor renal recovery in PE patients.

DOI： 10.1016/j.preghy.2021.05.015

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OBJECTIVES: Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. METHODS: Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. RESULTS: Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. CONCLUSION: Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

DOI： 10.1177/0961203320983906

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The COVID-19 pandemic might affect many aspects of the community and a range of psychiatric risk factors due to life changes, including people's behaviors and perceptions. In this study, we aim to identify specific life changes that correlate with psychological distress within the social context of the COVID-19 pandemic in Japan. In July 2020, workers (company employees and civil servants) in Japan were recruited from local institutions that had not had any confirmed COVID-19 cases as well as neighborhoods that had only a few cases. Participants completed a COVID-19 mental health survey (N = 609; 66.9% male). Psychological distress was identified based on Kessler-6 scores (≥13). Life changes were assessed by an open-ended question about life changes in participants and their family, workplace, and community due to the COVID-19 pandemic. A convergent mixed-method approach was used to compare the context of perceived life changes in participants with psychological distress and those without. As a result, 8.9% of participants had psychological distress, and sex and age categories were different between those with psychological distress and those without. Among the participants who responded to the open-ended question, the biggest life change was "staying at home," and the next biggest life changes were "event cancellations" and "increased workload" in participants with psychological distress, and "no changes" and "mask-wearing" in those without psychological distress, respectively. Regarding emotional/perceptual changes, "stress," "fear," and "anger" were more frequently reported by participants with psychological distress than those without (P <0.001). By integrating these findings, we identified themes focusing on vulnerable characteristics related to psychological distress. This study may provide a source in society for mediating psychological distress during a pandemic.

DOI： 10.1371/journal.pone.0256481

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BACKGROUND: Kidney dysfunction is associated with sarcopenia. Estimated glomerular filtration rate based on cystatin C (eGFRcys), an alternative to creatinine-based measures of kidney function eGFR, is not affected by muscle mass. Given that the association of eGFRcys with muscle weakness would be limited, we examined the association in older adults with normal or compromised kidney function. METHODS: This cross-sectional study involved 594 community-dwelling Japanese adults aged ≥40 years living in Yuzawa, Japan. Serum creatinine, cystatin C, and handgrip strength were concurrently measured at a health-check examination in 2015. eGFR was calculated according to the equation developed for the Japanese population using creatinine and cystatin C. Associations of eGFRcys and eGFRcreat with low grip strength (men, <26 kg and women, <18 kg) were analyzed using logistic regression models adjusted to control for potential confounders. RESULTS: Participants (mean age, 74.9 years) included 319 women and 109 individuals with low grip strength. Mean eGFRcys was 75.2 (SD 18.6) mL/min/1.73 m 2. Pearson's correlation coefficients of handgrip strength for eGFRcys and eGFRcreat were 0.19 (P < 0.001) and -0.04 (P = 0.281), respectively. Multivariate logistic regression analysis showed the adjusted odds ratio (OR) of low grip strength for the highest versus lowest quartile of eGFRcys value was 2.46 (95% confidence interval, 1.03-5.86; P-trend = 0.026); whereas the comparative adjusted OR for eGFRcreat was 0.67 (95% confidence interval, 0.34-1.32). CONCLUSION: Low kidney function as assessed by eGFRcys was associated with muscle weakness in community-dwelling Japanese older adults.

DOI： 10.1093/gerona/glaa240

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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BACKGROUND: Evidence for primary prevention of chronic kidney disease (CKD) is insufficient. The population-based prospective Uonuma CKD cohort study aims to explore associations of lifestyle and other risk factors with CKD. We report here the study design and baseline profiles. METHODS: All 67,322 residents aged ≥40 years in Minamiuonuma City, Uonuma City, and Yuzawa Town, Niigata Prefecture, Japan and 11,406 participants who attended local health-check examinations were targeted for baseline questionnaire and biochemical sampling, respectively. Information was gathered from 43,217 (64.2%) questionnaires and 8,052 (70.6%) biochemical samples; 6,945 participants consented to both questionnaire and biochemical sampling at baseline, conducted between fiscal years 2012 and 2015. Participants provided information regarding sociodemographic, lifestyle, and self-reported outcomes. Urine albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. The primary outcome is CKD based on self-report and biochemical/clinical diagnosis. RESULTS: Mean age of questionnaire respondents was 63.3 (standard deviation [SD], 12.5) years for men and 64.3 (SD, 13.3) years for women. Among participants who submitted urine samples, median ACR was 10.0 (interquartile range [IQR], 5.0-24.0) mg/g for men and 13.0 (IQR, 7.7-27.0) mg/g for women, and median eGFR was 73.6 mL/min/1.73 m2 (IQR, 63.5-84.5) for men and 73.5 mL/min/1.73 m2 (IQR, 64.4-83.5) for women. ACR 30 mg/g or more was found in 1,741 participants (21.7%) and eGFR <60 mL/min/1.73 m2 in 1,361 participants (16.9%). CONCLUSION: The Uonuma CKD cohort study was established to investigate the impact of lifestyle on CKD development and to provide data for preventing the onset and progression of CKD.

DOI： 10.2188/jea.JE20180220

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Positive associations between vitamin D levels and hand grip strength have been reported worldwide, but the results are not consistent and few studies on East Asian populations have been published. The aim of this study was to determine whether such an association is present in a community-dwelling Japanese population, including elderly and middle-aged individuals. This study used a cross-sectional design. Participants were 492 community-dwelling individuals aged ≥ 40 years living in Yuzawa Town, Japan. The health check examination was conducted in 2015, and serum 25-hydroxyvitamin D [25(OH)D, an index of vitamin D levels], and hand grip strength were measured. Covariates were serum albumin concentration, body mass index, and physical activity level. The associations of serum 25(OH)D concentrations with hand grip strength and low grip strength (< 26 kg for men and < 18 kg for women) were analyzed using analysis of covariance and multiple logistic regression. Mean (standard deviation) age and serum 25(OH)D were 75.4 (9.0) years and 30.9 (9.1) ng/mL, respectively. The prevalence of serum 25(OH)D < 20, 20-29, and ≥ 30 ng/mL was 7.3%, 37.8%, and 54.9%, respectively. Mean hand grip strength in the 25(OH)D < 20 ng/mL group was significantly lower than that in the ≥ 30 ng/mL group (adjusted P ≤ 0.001). The 25(OH)D < 20 ng/mL group was significantly more likely to have low grip strength than the 25(OH)D ≥ 30 ng/mL group (odds ratio = 4.12). In conclusion, low serum 25(OH)D concentration (< 20 ng/mL) is associated with low grip strength in an older Japanese population.

DOI： 10.1007/s00774-019-01040-w

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OBJECTIVE: Glomerular filtration rate (GFR) decreases without or prior to the development of albuminuria in many patients with diabetes. Therefore, albuminuria and/or a low GFR in patients with diabetes is referred to as diabetic kidney disease (DKD). A certain proportion of patients with diabetes show a rapid progressive decline in renal function in a unidirectional manner and are termed early decliners. This study aimed to elucidate the prevalence of DKD and early decliners and clarify their risk factors. RESEARCH DESIGN AND METHODS: This combination cross-sectional and cohort study included 2385 patients with diabetes from 15 hospitals. We defined DKD as a urinary albumin to creatinine ratio (ACR) ≥30 mg/gCr and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We classified patients into four groups based on the presence or absence of albuminuria and a decrease in eGFR to reveal the risk factors for DKD. We also performed a trajectory analysis and specified the prevalence and risk factors of early decliners with sequential eGFR data of 1955 patients in five facilities. RESULTS: Of our cohort, 52% had DKD. Above all, 12% with a low eGFR but no albuminuria had no traditional risk factors, such as elevated glycated hemoglobin, elevated blood pressure, or diabetic retinopathy in contrast to patients with albuminuria but normal eGFR. Additionally, 14% of our patients were early decliners. Older age, higher basal eGFR, higher ACR, and higher systolic blood pressure were significantly associated with early decliners. CONCLUSIONS: The prevalence of DKD in this cohort was larger than ever reported. By testing eGFR yearly and identifying risk factors in the early phase of diabetes, we can identify patients at high risk of developing end-stage renal disease.

DOI： 10.1136/bmjdrc-2019-000902

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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BACKGROUND: Although most cases of tubulointerstitial nephritis in paraproteinemia are monoclonal light chain deposition-mediated, interstitial nephritis as neoplastic interstitial cell infiltration has rarely been described. On the other hand, lympho-plasma-cell-rich tubulointerstitial nephritis, in which the infiltrative cells are usually polytypic, is often evident in primary Sjögren's syndrome (pSS). Herein we present a rare case of pSS in a patient who had been diagnosed as having IgA kappa-type monoclonal gammopathy of undetermined significance (MGUS) and developed tubulointerstitial nephritis with monotypic (IgA kappa) lympho-plasmacytic infiltrates. CASE PRESENTATION: A 74-year-old Japanese woman with pSS who had been diagnosed as having IgA kappa-type MGUS developed progressive renal dysfunction. Renal biopsy revealed tubulointerstitial nephritis with abundant plasma cell-rich mononuclear cell infiltrates without atypia. Immunohistochemical staining for immunoglobulins and light chains showed that most infiltrates were positive for IgA and kappa. Most of the infiltrative cells were positive for CD38 and CD138, and cells positive for CD 19 and CD 45 were also widely evident. Electron microscopy and immunofluorescence studies revealed no apparent immunological deposits in the glomeruli and tubules. Bone marrow and whole-body radiological examinations revealed no findings suggestive of multiple myeloma or lymphoma. Renal function improved rapidly with prednisolone 40 mg daily and has been maintained at the same level on low-dose prednisolone and azathioprine for 18 months. CONCLUSION: Tubulointerstitial nephritis with monotypic cell infiltrates, without immunological deposits, is a quite rare histological picture in MGUS, and might be a unique renal manifestation in patients with pSS.

DOI： 10.1186/s12882-019-1646-x

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OBJECTIVES: To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation and risk factors associated with this condition. METHODS: A total of 201 patients who received living-donor kidney transplantation (114 patients with ABO-identical kidney transplantation and 87 patients with ABO-incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti-A and anti-B antibodies were purified from human plasma, and these antibodies' bindings to human kidney were investigated in vitro. RESULTS: ABO-incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8-8.9, P < 0.001) after transplantation. Multivariate logistic regression analysis showed that non-use of mycophenolate mofetil, pretreatment immunoglobulin G antibody titer ≥64-fold and pretransplant immunoglobulin M antibody titer ≥16-fold were significant risk factors for systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation. Microvascular inflammation of 1-h post-transplant biopsy could be observed more frequently in thrombotic microangiopathy patients than in non-thrombotic microangiopathy patients. Anti-A and anti-B antibodies purified from human plasma showed a strong in vitro reaction against human kidney when the antibody titer was ≥16-fold. CONCLUSIONS: Antibody titer should be decreased to ≤16-fold until the day of ABO-incompatible kidney transplantation by desensitization therapy including mycophenolate mofetil. The 1-h biopsy results might help to diagnose systemic de novo thrombotic microangiopathy.

DOI： 10.1111/iju.14118

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Plasma cell-rich acute rejection (PCAR) and antibody-mediated rejection (ABMR), for which a standard treatment has not yet been established, are associated with poor graft survival after kidney transplantation. Here, we report a case series of 3 Japanese patients diagnosed with PCAR accompanied by ABMR. Steroid pulse therapy and rabbit antithymocyte globulin, plasma exchange, intravenous immunoglobulin, and rituximab therapies were sequentially performed in the first case. A graft biopsy after each treatment showed that plasma cell infiltration persisted. Five months after the initiation of rejection therapy, the patient was subjected to bortezomib therapy, which led to the partial elimination of plasma cells from the graft. However, the graft function gradually deteriorated, and hemodialysis treatment was warranted. In the other 2 cases, the patients received the same combination of therapy including bortezomib within a short period. Graft biopsies performed subsequently showed a marked decrease in the number of infiltrated plasma cells, and stabilization of renal graft function was achieved in both cases. Bortezomib, which targets plasma cells, is a potent drug that eliminates infiltrated plasma cells from the graft in PCAR. Thus, in addition to conventional therapy comprising plasma exchange, intravenous immunoglobulin, and rituximab against ABMR, bortezomib may be necessary to administer without any delay to control PCAR.

DOI： 10.1016/j.transproceed.2019.02.038

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DOI： 10.1007/s13730-019-00409-0

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BACKGROUND: Acid-base imbalance might promote the progression of chronic kidney disease (CKD), but whether nutrient-derived dietary acid load increases the risk of albuminuria or even high normoalbuminuria is unclear. METHODS: A Japanese cohort comprising 3250 men and 3434 women aged 40-97 years with urine albumin-to-creatinine ratio (ACR) < 33.9 mg/mmol or estimated glomerular filtration rate ≥ 15 ml/min/1.73 m2 were assessed. We performed a cross-sectional evaluation of the association between net endogenous acid production (NEAP), estimated as dietary protein to potassium content ratio, and the presence of high normoalbuminuria (ACR: 1.13-3.38 mg/mmol) or microalbuminuria. RESULTS: Median NEAP was 43.4 (interquartile range (IQR): 34.2-53.4) mEq/day in men and 35.0 (IQR: 27.7-43.6) mEq/day in women. Median ACR was 1.11 (IQR: 0.57-2.49) mg/mmol in men and 1.47 (IQR: 0.82-2.83) mg/mmol in women. In multivariate analysis, the adjusted odds ratio of the highest versus lowest NEAP quartile for microalbuminuria was 1.47 (95% confidence interval (CI): 1.08-1.99) in men and 1.54 (95% CI: 1.11-2.14) in women. For high normoalbuminuria or microalbuminuria, the adjusted odds ratio was 1.28 (95% CI: 1.02-1.59) in men and 1.39 (95% CI: 1.11-1.74) in women. From nutrient composition analysis, subjects with the highest potassium intake, but not protein intake, had lower adjusted odds ratios for the presence of microalbuminuria than those in the lowest quartile for potassium intake. CONCLUSIONS: Higher NEAP was associated with albuminuria and its association might negatively relate to potassium intake in an adult Japanese population.

DOI： 10.1186/s12882-019-1352-8

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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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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DOI： 10.1080/13506129.2019.1582512

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Language：Japanese   Publisher：THE JAPANESE UROLOGICAL ASSOCIATION  

<p> (Background) The standard treatment for recurrent immunoglobulin A nephropathy (rIgAN) after kidney transplantation (KTx) has not been established.</p><p> (Methods) The results of treatment consisting of tonsillectomy and steroid pulse therapy in 20 recipients who were diagnosed as rIgAN were retrospectively analyzed.</p><p> (Results) The level of proteinuria significantly decreased from 0.84±0.81 g/day to 0.27±0.31 g/day after treatment (P=0.007). Microscopic hematuria disappeared or improved in 58.3% and 66.6% of recipients 6 and 12 months after treatment, respectively. Serum creatinine levels remained stable for 5 years by the treatment, except for 3 cases of graft loss. Sixteen recipients received renal graft biopsies before and after treatment. Mesangial IgA deposition were dramatically decreased in 7 recipients (43.75%). The degree of mesangial hypercellularity, endocapillary hypercellularity, and crescents formation improved in 3 (18.8%), 6 (37.5%), and 4 (25%) recipients after treatment.</p><p> (Conclusion) Steroid pulse therapy combined with tonsillectomy may be clinically and histopathologically effective treatment for rIgAN after KTx.</p>

DOI： 10.5980/jpnjurol.110.92

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A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Glatm mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the GlatmTg(CAG-A4GALT) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure ( i.e., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules-Na+-K+-ATPase, uromodulin, and Na+-K+-2Cl- cotransporter-that are involved in Na+ reabsorption in mTALs and the associated loss of urine-concentrating ability resulted in progressive water- and salt-loss phenotypes. GlatmTg(CAG-A4GALT) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes polyuria and renal impairment and contributes to the pathophysiology of Fabry nephropathy.-Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the GlatmTg(CAG-A4GALT) Fabry model mice.

DOI： 10.1096/fj.201701374R

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Emotional disturbance including depression is associated with increased mortality among dialysis patients. The Self-Rating Depression Scale (SDS) is a simple tool for assessing emotional disturbance. This study investigated the relationship between emotional conditions as assessed with the SDS test and mortality among 491 hemodialysis patients. At baseline, 183 (37.3%), 180 (36.7%), 108 (22.0%), and 20 (4.1%) were classified as normal, borderline depression, depression, and severe depression, respectively. During the two years of observation period, 57 of 491 (11.6%) died. The SDS scores in the non-survivors were significantly higher than those in the survivors (p<0.0001). Logistic analyses showed that the diagnoses made by the SDS test were associated with significantly greater risks for all-cause mortality (99%CI: 1.905-3.698 for that without adjustment, 1.999-4.382 for that with full adjustment). When the SDS score = 50 was selected as the cut off value, the test screened two-year all cause death with sensitivity = 57.9% and the specificity = 78.1%. In conclusion, hemodialysis patients had high prevalence of emotional disturbance assessed by the SDS test, and high SDS score was significantly associated with all-cause mortality. These findings underscore the importance of screening for emotional conditions using the SDS test among hemodialysis patients.

DOI： 10.5387/fms.2016-21

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NEPHROLOGY  

Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologicfindings were interstitial nephritis with diffusely distributed CD3-positiveT lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3--Cl- anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell-tubulointerstitial nephritis.

DOI： 10.1681/ASN.2016101074

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log10%amyloid). The results of sex-, age-, and Log10%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

DOI： 10.1080/13506129.2017.1338565

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Language：Japanese   Publisher：腎移植・血管外科研究会  

移植医療におけるドナー不足は大きな問題であり、高齢者ドナーや心停止後摘出臓器の利用が世界的にも増加している。移植後の腎機能に影響する因子を検討することは以前より行われてきた。当院における59例の心停止下献腎移植の移植腎機能にかかわるレシピエント因子、ドナー因子、graft因子をそれぞれ後方視的に解析した。その結果、UNOSの定義するExpanded criteria donor(ECD)とgraft hyalinosisの程度が移植後腎機能に大きく影響する因子であることが分かった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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DOI： 10.1080/13506129.2017.1291421

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The mechanism of long-term B cell immunity against donor blood group antigens in recipients who undergo ABO-incompatible (ABOi) living-donor kidney transplantation (LKTx) is unknown. To address this question, we evaluated serial anti-A and anti-B antibody titers in 50 adult recipients. Donor-specific antibody titers remained low (≤1:4) in 42 recipients (84%). However, antibodies against nondonor blood group antigens were continuously produced in recipients with blood type O. We stimulated recipients' peripheral blood mononuclear cells in vitro to investigate whether B cells produced antibodies against donor blood group antigens in the absence of graft adsorption in vivo. Antibodies in cell culture supernatant were measured using specific enzyme-linked immunosorbent assays (ELISAs). Thirty-five healthy volunteers and 57 recipients who underwent ABO-compatible LKTx served as controls. Antibody production in vitro against donor blood group antigens by cells from ABOi LKTx patients was lower than in the control groups. Immunoglobulin deposits were undetectable in biopsies of grafts of eight recipients with low antibody titers (≤1:4) after ABOi LKTx. One patient with blood type A1 who received a second ABOi LKTx from a type B donor did not produce B-specific antibodies. These findings suggest diminished donor-specific antibody production function in the setting of adult ABOi LKTx.

DOI： 10.1111/ajt.13937

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

BACKGROUND: 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. METHODS: 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 ≥ 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). RESULTS: In univariate analyses, the kidney survival rate was significantly lower in patients with Ex1 and A1 if UP ≥ 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 ≥ 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. CONCLUSION: Ex and A would be associated with the renal outcome of the patients with UP ≥ 0.5 g/day.

DOI： 10.1007/s10157-015-1185-0

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer Japan  

A 74-year-old woman presented with a 1-year history of dry mouth. She had also noticed bilateral submandibular and parotid swelling 6 months before she visited the otolaryngology department of our hospital. Contrast-enhanced computed tomography showed multiple hilar and mediastinal lymphadenopathy, diffuse enlargement of the pancreas with partial narrowing of the main pancreatic duct, and multiple low-density areas in the bilateral kidneys. There was marked elevation of the serum IgG, IgG4, and IgE levels, together with tubulointerstitial dysfunction, compatible with IgG4-RD. Pancytopenia, positivity for antinuclear antibody and anti-double-stranded DNA antibody, and marked hypocomplementemia were also observed, all consistent with systemic lupus erythematosus (SLE). Percutaneous kidney biopsy revealed no significant abnormality in the glomeruli by light microscopy. In tubulointerstitial areas, well circumscribed areas of intense lymphoplasmacytic infiltration accompanied by mild fibrotic changes were evident, and immunohistochemistry demonstrated marked infiltration of IgG4-positive plasma cells. The immunofluorescence studies, however, revealed diffuse mesangial and capillary deposition of IgG, IgA, IgM, C1q, and C3c in the glomeruli, being typical of lupus nephritis. This case demonstrates the concurrent development of both IgG4-RD and SLE, suggesting the possibility of common pathophysiological mechanisms.

DOI： 10.1007/978-4-431-55687-9_27

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Objective Ultrastructural studies of IgG4-related kidney disease (IgG4-RKD) characterized by tubulointerstitial nephritis (TIN) are limited in previous reports due to the rarity of the condition. In the present report, we performed ultrastructural examinations and assessed the pathogenesis of this disease.
Patients Clinicopathological studies were conducted in eight patients diagnosed with IgG4-RKD. Routine light, immunofluorescence and electron microscopy examinations and immunohistochemical assessments of IgG4 were performed using renal biopsy samples.
Results Hypocomplementemia, positive anti-nuclear antibodies and eosinophilia were confirmed in more than half of the cases. Electron dense deposits (EDDs) were frequently found in the glomeruli and interstitium. The rate of deposition was 62.5% in both mesangial areas and Bowman's capsule. EDDs were frequently detected on the tubular basement membrane (TBM) (87.5% of patients). The interstitium also contained EDDs on collagen fibers in 87.5% of the cases and on basement membrane-like materials in areas of fibrosis in 37.5% of the cases. The creatinine clearance levels were significantly lower in the patients with the latter pattern. Meanwhile, the rate of immunoglobulin and/or complement deposition on the TBM was observed in less than 37.5% of patients, and these findings were not entirely coincident with the cases of EDDs on the TBM.
Conclusion EDDs are frequently found in the glomeruli and interstitium in patients with IgG4-RKD; however, immunohistological studies do not provide evidence that IgG4-RKD involves TIN with immune complex nephropathy. The presence of interstitial EDDs may be related to the progression of interstitial fibrosis in the setting of IgG4-RKD.

DOI： 10.2169/internalmedicine.54.2581

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A 47-year-old Japanese man was admitted to our hospital for evaluation of proteinuria, which was detected when he was 37 years of age. His creatinine clearance levels had fallen to 76.3 mL/min/1.73 m2. A kidney biopsy was conducted, and the patient's low plasma α-galactosidase A levels suggested Fabry disease. After genetic counseling, GLA analysis revealed a novel mutation p.L387P. Interview with the patient revealed that both his younger brother and mother suffered from cardiomyopathy and were undergoing cardiological treatment. They also were positive for proteinuria. About 30 years ago, the patient's cousin (aged 25) was diagnosed with Fabry disease. He underwent hemodialysis for 9 years until his death at 42. At that time, the patient and his brother had not been investigated for Fabry disease so their cousin could not act as a proband for the brothers. Eventually, the patient, his mother, and his brother were put on enzyme replacement therapy with agalsidase beta. As this series of cases shows, medical interviews to collate both medical and family history were essential for the discovery of Fabry disease in these patients. In addition, being a treatable genetic disorder, Fabry disease should be listed in the standard differential diagnoses of systemic and familial diseases, including unknown cause of nephropathy or cardiomyopathy, for early detection of the disorder.

DOI： 10.1007/s13730-014-0108-3

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The sequential or simultaneous presentation of anti-glomerular basement membrane (anti-GBM) glomerulonephritis with membranous nephropathy (MN) has been infrequently reported. Although the mechanism underlying MN superimposed on anti-GBM glomerulonephritis is unknown, the two entities are believed to be interrelated. We report the case of a 75-year-old woman diagnosed with rapidly progressive glomerulonephritis. Renal biopsy revealed crescentic glomerulonephritis with linear and granular staining of immunofluorescent IgG1 and IgG4 granular staining on the capillary loops. Electron microscopy revealed extensive subepithelial deposits. These findings suggested simultaneous development of anti-GBM glomerulonephritis and MN in this case. Serum phospholipase A2 receptor (PLA2R) antibody was negative. The patient was treated with prednisolone and plasma exchange, resulting in resolution of renal insufficiency and a decrease in urinary protein. The rapid decrease in urinary protein and absence of PLA2R antibody suggest that the mechanism of MN associated with anti-GBM glomerulonephritis differs from that of primary MN.

DOI： 10.1007/s13730-013-0094-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 69-year-old man presented with proteinuria and hematuria. He had received total parenteral nutrition for massive small bowel resection. However, due to the iatrogenic lack of trace elements for the next four years, he developed severe copper-deficiency anemia and neutropenia. In addition, his proteinuria and kidney dysfunction worsened concurrently with the development of nephrotic syndrome and end-stage kidney disease. After receiving trace elements, the patient's anemia and neutropenia improved, and the anuria dramatically resolved. Copper-containing enzymes, including ceruloplasmin have an antioxidant activity. In patients with various types of glomerular injuries, the ceruloplasmin expression is known to be increased. Copper deficiency can worsen nephrotic syndrome by decreasing the ceruloplasmin activity, which protects the glomeruli.

DOI： 10.2169/internalmedicine.53.2338

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BACKGROUND: Patient and graft survival after successful kidney transplantation (KT) have improved despite an increase in the number of challenging cases. Various factors have evolved during the long history of kidney transplantation. METHODS: Between 1988 and 2012, a total of 292 living donor and 56 deceased donor KTs were performed at Niigata University Hospital. Long-term patient and graft survival and changes in background during a 20-year period in a single center were retrospectively analyzed. RESULTS: Excellent patient survival rates of 95.1% at 20 years for living donor KT and 96.2% at 15 years for deceased donor KT were observed. Graft survival rates at 1, 5, 10, 15, and 20 years were 96.8%, 95.4%, 83.1%, 61.8%, and 56.2% in living donor KT, respectively. In contrast, graft survival rates at 1, 5, 10, and 15 years in deceased donor KT were 89.0%, 80.3%, 77.3%, and 33.8%, respectively. These survival rates have dramatically improved since 2002 (91.7% for living and 80.9% for deceased donor KT at 10 years post-transplantation). The number of elderly recipients (older than 60 years) and the percentage of grafts donated from spouses have increased. The rejection rate decreased and the cytomegalovirus antigenemia-positive rate increased during the 20-year period assessed. The percentage of pre-emptive KTs progressively increased, with graft survival in this group tending to be better than non-preemptive KTs. The causes of graft loss were chronic allograft dysfunction (54.7%), acute rejection (11.1%), and malignancies (9.4%). After living donor KT, the principal predictors of graft loss were if the recipient was younger than 30 years, if the donor was older than 50 years, and if the rejection episodes occurred after living donor KT. In contrast, the only risk factor in the case of deceased donor KT occurred after transplantation from donors who were older than 50 years. CONCLUSIONS: A summary of the long-term outcome of KT over 20 years in a single center has been reported. Along with the changes in patient backgrounds, immunosuppressive drugs, and our knowledge of transplantation, patient and graft survival outcomes have also changed. Investigation into such outcomes during a different transplantation era is required to fully appreciate advances in KT.

DOI： 10.1016/j.transproceed.2013.10.052

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Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal-dominant disorder that is characterized by hyperuricemia and chronic renal failure and results in end-stage renal failure. FJHN is caused by mutations in the UMOD gene, which encodes uromodulin. Uromodulin contains three epidermal growth factor (EGF)-like domains, a domain of eight cysteine residues (D8C), and a zona pellucid-like domain. Over 90 % of UMOD mutations are missense mutations, and over 80 % exist in exon 4, which encodes both D8C and the EGF-like domains. A 56-year-old woman was diagnosed with hyperuricemia with a serum uric acid level of 7.5 mg/dL, and stage III chronic kidney disease (CKD) with a serum creatinine level of 1.12 mg/dL and an estimated glomerular filtration rate of 39.9 mL/(min 1.73 m2). The patient had a family history of hyperuricemia and stage IV CKD; both the patient and her affected family members had a novel mutation in the UMOD gene: c.C518G (p.P173R), located between the EGF-like domains and D8C. This mutation, along with previously reported nearby mutations, causes a clinically mild phenotype of FJHN. It is important that physicians consider the diagnosis of FJHN in patients with a family history of hyperuricemia associated with renal dysfunction, even if the patient has only mild renal impairment.

DOI： 10.1007/s13730-013-0069-y

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A 31-year-old woman with proteinuria, hypocomplementemia, rheumatoid factor, and high serum polyclonal IgM concentration was admitted to our hospital for renal biopsy. She had a past history of two renal biopsies. When she was 12 years old, she developed proteinuria, microscopic hematuria, and hypocomplementemia. She was diagnosed as having 'IgM nephropathy' based on minor glomerular abnormalities as determined by light microscopy and IgM and C3 deposition in the mesangial region by immunofluorescence microscopy at the first biopsy. Despite corticosteroid treatment, her proteinuria did not improve and she discontinued regular outpatient checkups. When she was 29 years old and pregnant, she developed preeclampsia and, after delivery, a second renal biopsy was implemented. She was diagnosed as having progressed 'IgM nephropathy' with endotheliosis induced by preeclampsia. She was treated with angiotensin II receptor blocker and her proteinuria diminished; however, 1 year after the delivery, she developed proteinuria again, along with microscopic hematuria and hypocomplementemia. A third renal biopsy was conducted at 31 years of age and she was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type I on the basis of diffuse mesangial proliferation, endocapillary hypercellularity with double contour of the capillary wall, and lobular formation in glomeruli, as determined by light microscopy. Immunofluorescence staining demonstrated deposits of C3, C4, C1q, and IgM in the mesangial region and capillary wall. She underwent corticosteroid therapy followed by normalization of urinalysis and serum complement level. Although she had initially been diagnosed with 'IgM nephropathy', she was finally diagnosed with secondary MPGN and was successfully treated by corticosteroid therapy.

DOI： 10.1007/s13730-012-0042-1

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Podocytic infolding glomerulopathy (PIG) has been proposed as a new disease entity. A 14-year-old girl underwent renal biopsy at our institution because of a chance finding of proteinuria. Light microscopic findings revealed a minor glomerular abnormality, but under a higher magnification, after periodic acid methenamine silver staining, a bubbling appearance in the glomerular basement membrane (GBM) was observed. An electron microscopic examination revealed microspheres in the GBM, which were sparse but global. The patient was diagnosed as having PIG. After 3 years, her urinary protein had increased and a second biopsy was performed, showing focal segmental glomerulosclerosis in addition to a lesser degree of podocytic infolding than at the first biopsy. This is the first report of a case complicated by a different type of glomerulonephritis after being diagnosed as PIG. A few cases of PIG are complicated by focal segmental glomerulosclerosis, suggesting several mechanisms for the disorder.

DOI： 10.1159/000354591

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Pentraxin-3 (PTX3) is an acute phase reactant produced by a variety of cell types at sites of local inflammation. We examined by immunohistochemistry renal biopsies from patients with acute rejection (n = 10), protocol biopsies without rejection (n = 37), and peri-operative donor biopsies of the same transplant patients (n = 94) for intra-renal expression of PTX3, and its correlation with clinical, laboratory, and histopathologic parameters. PTX3 was mainly expressed in the interstitium of renal allograft. In the non-rejection biopsies (pre- and post-reperfusion and protocol biopsies), PTX3 expression area (PTX3%) was equally maintained at a low level, whereas in the rejection biopsies, PTX3% was significantly higher (p < 0.0001). Treatment of acute rejection resulted in a significant reduction of PTX3% (p < 0.0001). PTX3% positively correlated with the degree of allograft dysfunction and acute rejection scores of Banff classification (2009). This study suggests that PTX3% may be an available histological marker of acute renal allograft rejection.

DOI： 10.1111/j.1399-0012.2012.01641.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

BACKGROUND: IgG4-related disease is a multi-organ disorder characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive cells into affected organs. In routine studies, however, IgG subclasses are not estimated. In the present study, we attempted to clarify the light-microscopic characteristics of IgG4-related tubulointerstitial nephritis (TIN) to facilitate distinction from non-IgG4-related TIN in specimens obtained by renal biopsy using routine staining. METHODS: In specimens from 34 cases of TIN (13 IgG4-related and 21 non-IgG4-related), 9 nephrologists independently reviewed the following histological features of interstitial lesions: (i) cell infiltration extending into the renal capsule, (ii) cell infiltration into the renal medulla, (iii) regional lesion distribution, (iv) lymphoid follicles, (v) granulomatous lesions, (vi) necrotizing angiitis, (vii) eosinophil infiltration, (viii) neutrophil infiltration, (ix) tubulitis, (x) peritubular capillaritis, (xi) storiform fibrosis and (xii) the stage of interstitial fibrosis. The modified nominal group technique was applied to obtain a consensus in the pathological interpretation. RESULTS: Consensus was successfully attained among the diagnosticians for all but one pathological feature (regional lesion distribution). Storiform fibrosis was demonstrated in 12 of 13 (92.3%) cases of IgG4-related TIN but in none of the cases of other types of TIN. Cell infiltration extending into the renal capsule was also observed only in IgG4-related TIN. Conversely, neutrophil infiltration, severe tubulitis, severe peritubular capillaritis, granulomatous lesions and necrotizing angiitis were evident only in non-IgG4-related TIN. CONCLUSIONS: This study revealed some useful and characteristic features for distinguishing IgG4-related from non-IgG4-related TIN on the basis of light-microscopic observation.

DOI： 10.1093/ndt/gfr761

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Immunoglobulin (Ig) G4-related kidney disease characterizing tubulointerstitial nephritis (TIN) is an organ complication recognized in IgG4-related systemic diseases that has some unique aspects compared to other types of TIN. TIN lesions in the kidney can be tumor-like, focal or diffuse. Abnormal urinalysis is usually mild or absent even in the cases with deteriorated renal dysfunction. Some cases are accidentally diagnosed from radiological findings without renal dysfunction and/or abnormal urinalysis. The typical pathological findings of TIN are unique fibrosis and infiltration of massive lymphocytes and IgG4-positive plasma cells. Glomerular lesions are rare but the complication of mesangial proliferative glomerulonephritis and membranous nephropathy is occasionally reported. Pathogenic mechanisms are unclear until now; however, auto-immune and allergic mechanisms have been suspected from laboratory data. The initial response to steroid agents is generally favorable; however, recurrence is possible after the discontinuation of steroid treatment. Long-term follow-up is necessary with continuous systemic checks for organ disorders due to IgG4-related systemic diseases.

DOI： 10.1007/s10157-011-0526-x

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BK virus (BKV) nephropathy is one of the major causes of allograft dysfunction or graft loss in kidney transplant recipients. Early diagnosis and timely reduction in immunosuppressant is important for proper treatment. We report a 35-yr-old male case of cadaveric renal transplantation with BK viral related tubulointerstitial nephritis complicated by acute rejection. The diagnostic biopsy showed severe inflammatory infiltrates, tubulitis, and peritubular capillaritis. Discontinuation of mycophenolate mofetil, prednisone pulse therapy, and r-globulin was successful in relieving allograft dysfunction.

DOI： 10.1111/j.1399-0012.2011.01481.x

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At the age of three yr, a male patient had surgical treatment for bilateral vesicoureteral reflux (VUR), and at the age of 19 yr, he developed nephrotic syndrome because of focal segmental glomerulosclerosis (FSGS). His renal function deteriorated despite treatment with temocapril and aspirin, and dialysis treatment was started when he was 19. After nine yr of dialysis, he received a living kidney transplantation from his 58-yr-old father, who had a long history of hypertension. A graft biopsy before perfusion showed moderate arteriolosclerosis. As urine protein increased to 2.15 g/d at 16 months after kidney transplantation, the graft biopsy was performed again. FSGS lesion with severe arteriosclerosis was recognized under light microscope, while the effacement of podocyte foot processes was seldom observed. The alteration of calcineurin inhibitor from cyclosporine to tacrolimus, combined with the new administration of angiotensin receptor antagonist (valsartan) and aldosterone receptor blocker, successfully decreased the amount of urine protein to 0.8 g/d within two wk. We considered that the present case showed two distinct types of FSGS lesions--one because of VUR and the other because of cyclosporine arteriolopathy--in each native kidney and transplanted kidney.

DOI： 10.1111/j.1399-0012.2010.01267.x

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Calcitriol therapy is a central strategy for the treatment of uremic secondary hyperparathyroidism. Although indiscriminate use of calcitriol may lead to worse outcomes, it is difficult to make a decision to discontinue calcitriol therapy when its parathyroid suppression effect remains unsatisfactory. In this study, intravenous calcitriol was administered to 120 chronic hemodialysis patients. Therapy continued for 48 weeks or until plasma intact parathyroid hormone (iPTH) levels decreased to below 300 pg/ml or until the development of any significant adverse effect. Of the 120 patients, the treatment goal was achieved in 47 patients during the first 4 weeks, in 10 during the next 4 weeks, and in 22 patients thereafter. Logistic regression analysis and stepwise regression analysis revealed that iPTH levels were the only significant predictor of the response to calcitriol therapy at weeks 0 and 4. Besides iPTH, the inorganic phosphate (P) levels were another significant predictor of the ultimate response to calcitriol therapy at week 8. The point of best discrimination for successful treatment was P = 6.0 mg/dl at week 8, or P level at week 8/pretreatment P level = 1.0. In conclusion, the P level at week 8 is a predictor of the response to calcitriol therapy for uremic secondary hyperparathyroidism. Changes in treatment are recommended if patients show unsatisfactory parathyroid suppression with a hyperphosphatemic tendency.

DOI： 10.1007/s00774-007-0809-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastic formation and activity. Circulating OPG levels are elevated in uremia. The role of elevated circulating OPG levels in uremia remains unknown. Blood samples were obtained from 22 non-diabetic dialysis patients who underwent iliac bone biopsy examination. The serum OPG concentration was assayed by ELISA. The circulating OPG levels showed a negative correlation with the ratio of eroded surface/bone surface (ES/BS) in biopsied iliac bone samples among 15 of those with plasma intact PTH levels less than 300 pg/mL (P < 0.05, r(2) = 0.270). Patients with serum OPG levels less than 2.0 ng/mL showed significantly greater ES/BS values than those with levels > or =3.0 ng/mL, while the intact PTH levels were comparable among those groups. These tendencies disappeared when seven patients with plasma intact PTH levels more than 300 pg/mL were included into the analysis. In conclusion, circulating OPG levels showed a significant negative correlation with a bone resorption parameters in dialysis patients with mild secondary hyperparathyroidism. Circulating OPG might have a suppressive effect on osteoclastic bone resorption in dialysis patients.

DOI： 10.1111/j.1744-9987.2006.00375.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

Abeta-2M-amyloidosis is a type of systemic amyloidosis that is specifically seen in patients with chronic kidney diseases. The precursor protein of Abeta-2M-amyloid fibril is beta2-microglobulin, and its elevated serum level is the main cause of Abeta-2M-amyloidosis in patients with kidney failure. However, the precise mechanism of Abeta-2M-amyloidogenesis remains unclear. In vitro analyses of Abeta-2M amyloidogenesis are still being actively conducted. Osteolytic lesions are often found around synovial membrane with Abeta-2M-amyloid deposition. Both evident osteoclastogenesis and active osteoclastic bone resorption are found, while osteoblastic bone formation is absent in the lesion most likely associated with the inflammation caused by infiltrating macrophages/monocytes into Abeta-2M-amyloid deposition. The precise cell biological mechanism of this inflammatory change is unknown. Further studies are needed to establish specific treatments against this as yet unsolved problem with long-term dialysis therapy.

DOI： 10.1007/s00774-005-0669-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DUSTRI-VERLAG DR KARL FEISTLE  

Background: Osteoprotegerin is a natural glycoprotein which plays a critical role in osteoclast physiology. Elevated levels of circulating osteoprotegerin may account for the development of bone and mineral metabolic abnormalities in uremia. Little is known about the effects of vitamin D therapy on the circulating osteoprotegerin levels in dialysis patients. Patients and methods: Fifty chronic dialysis patients whose plasma intact PTH levels were greater than 300 pg/ml were analyzed for the study. Following a four-week washout time during which all vitamin D administration was halted, 10 mu g of maxacalcitol was intravenously injected thrice a week. Results: The circulating intact PTH, bone-specific alkaline phosphatase and intact osteocalcin levels were significantly lowered, while the serum calcium levels were elevated after the therapy. The osteoprotegerin levels significantly decreased after the therapy (p &lt; 0.0001). Conclusion: Maxacalcitol therapy reduced the circulating osteoprotegerin levels and improved secondary hyperparathyroidism. The observed effects were the opposite of those expected from previous in vitro studies. Osteoprotegerin may mediate and/or modify the effect of active vitamin D therapy in dialysis patients.

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BACKGROUND: The treatment strategy for secondary hyperparathyroidism is generally determined empirically with regards to present parathyroid function and serum calcium (Ca) and inorganic phosphate (Pi) levels. More evidence is needed to avoid the aimless continuation of active vitamin D therapy. METHODS: Nondiabetic dialysis patients whose plasma intact parathyroid hormone (iPTH) levels were greater than 300 pg/ml were included in the study. Maxacalcitol was intravenously injected three times a week. The treatment was continued for 48 weeks, unless the iPTH level was reduced to less than 300 pg/ml or unfavorable events occurred. The patients whose plasma iPTH levels were below 300 pg/ml within 48 weeks were defined as those who had been successfully treated. RESULTS: Findings for 146 patients were analyzed, and 96 patients were successfully treated. Serum Pi levels did not significantly increase during the therapy. The pretreatment plasma iPTH levels and serum Ca levels were lower in the patients who were successfully treated with maxacalcitol. A logistic regression study and classifying by stratum analyses revealed that the pretreatment serum Ca levels and plasma iPTH levels were significantly related to the result of maxacalcitol therapy, while the serum Pi levels were not. Analyses using a receiver-operating characteristic curve revealed that the areas under curves obtained for iPTH and Ca were significantly greater than those obtained for Pi (P < 0.0001). CONCLUSIONS: Serum Ca levels and parathyroid function were correlated with the results of maxacalcitol therapy. Pretreatment serum Pi levels could not predict the result.

DOI： 10.1007/s10157-005-0342-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING INC  

Background. Glomerular accmulation of leukocytes, including lymphocytes, is a common feature in most types of glomerulonephritis. However, the role of lymphocytes in progressive glomerulonephritis has not been elucidated. We examined the role of lymphocytes in the development of progressive mesangial proliferative glomerulonephritis induced by two injections of monoclonal antibody 1-22-3 in rats.
Methods. To elucidate the role of lymphocytes, circulating lymphocytes were depleted using specific monoclonal antibodies to rat lymphocytes prior to the induction of progressive glomerulonephritis. The effects of lymphocyte depletion on proteinuria and glomerular alterations were assessed 7 and 56 days after the induction of progressive glomerulonephritis.
Results. Significant glomerular accmulation of CD4+ T cells, CD8+ T cells, and ED3+-activated macrophage were observed after the induction of glomerulonephritis. Depletion studies showed that continuous treatment with anti-CD5, anti-CD4, or anti-CD8 treatment reduced proteinuria and ameliorated the glomerular lesions on day 56. Depletion of CD4+ T cells also reduced glomerular accmulation of CD8+ T cells and ED3+-activated macrophages, and reduced glomerular expression of mRNA for interferon-gamma (INF-gamma) (63.0% in anti-CD5 and 62.3% reduction in anti-CD4). Transit lymphocyte depletion limited in early stage of progressive glomerulonephritis demonstrated that CD4+ T-cell depletion, but not anti-CD8 treatment prevented glomerular injuries 56 days after the induction of progressive glomerulonephritis.
Conclusion. CD4+ T cells played a central role in the development of progressive glomerulonephritis, controlling recruitment and activation of CD8+ cytotoxic cells and/or macrophages.

DOI： 10.1111/j.1523-1755.2004.00852.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

BACKGROUND: Although the so-called intact parathyroid hormone (iPTH) assay detects not only true 1-84 PTH (1-84PTH) but also large C-terminal PTH fragments, it remains inconclusive whether the 1-84PTH assay is more useful in clinical practice. Previous studies have shown that the results of these two PTH assays in dialysis patients are closely correlated. METHODS: Chronic dialysis patients whose plasma iPTH levels were >400 pg/ml were selected for inclusion in the present study. Following a 4 week wash-out time during which all vitamin D administration was halted, maxacalcitol was intravenously injected at the end of dialysis sessions three times per week for 24 weeks, at an initial dosage of 10 micro g. RESULTS: Ninety-seven patients with secondary hyperparathyroidism were included in our analysis. Their serum calcium levels were elevated from the start levels while phosphate levels remained unchanged. The plasma 1-84PTH levels constantly declined throughout the 24 weeks. Although the patients' plasma 1-84PTH and iPTH levels were closely correlated with each other both at the beginning of the study and after 24 weeks of maxacalcitol therapy, the ratio of 1-84PTH/iPTH consistently decreased throughout the study period (P<0.01). The changes in the ratio were significantly correlated with changes in serum calcium levels. CONCLUSIONS: Twenty-four weeks of intravenous maxacalcitol injection therapy significantly reduced the 1-84PTH/iPTH ratio. Estimated 1-84PTH levels from iPTH levels using a conversion formula obtained before the treatment were 21.0+/-20.4% higher than measured 1-84PTH levels after the therapy. Thus, iPTH measurement has a potential risk to overestimate 1-84PTH levels when evaluating the efficacy of maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

DOI： 10.1093/ndt/gfh038

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL MUNKSGAARD  

In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack. complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.

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In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejedion, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cell. © Blackwell Munksgaard, 2004.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DUSTRI-VERLAG DR KARL FEISTLE  

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.

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Background. We established the reversible and the prolonged models of mesangial proliferative glomerulonephritis (GN) with anti-Thy 1 antibody 1-22-3. However, the essential factors leading to the prolonged glomerular alterations have not been identified.
Methods. The expressions of several chemokines and cytokines were compared in the reversible and the prolonged models. Expression of fractalkine and the number of the fractalkine receptor CX3 CR1-positive cells in the glomeruli in the prolonged model were significantly higher than those in the reversible model. Then, the localization of fractalkine and the characteristics of CX3 CR1(+) cells were analyzed in glomeruli. To elucidate the significance of the fractalkine expression, we analyzed the expression in the model treated with angiotensin II receptor antagonist, candesartan.
Results. Immunostaining of fractalkine was detected on endothelial cells on the fifth day, and fractalkine staining also was detected in the mesangial area on day 14. Major parts of the CX3 CR1(+) cells in the glomeruli were macrophages, especially ED3(+) cells. Candesartan treatment ameliorated the glomerular morphological findings at six weeks after disease induction. Although the treatment did not ameliorate the morphological finding at two weeks, decreased expression of fractalkine and CX3 CR1(+) were already detected at two weeks in rats treated with candesartan.
Conclusions. Fractalkine expression and the recruitment of CX3 CR1(+) cells in glomeruli might play an important role in the development of the prolonged disease. These expressions could be predictors of the prolonged disease of the mesangial proliferative glomerulonephritis.

DOI： 10.1046/j.1523-1755.2002.00369.x

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DOI： 10.1046/j.1523-1755.2001.00047.x

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DOI： 10.1159/000046117

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The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11 weeks. Repeated administration of the plasmid DNA effectively produced erythropoiesis. Similar erythropoiesis was observed in the uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the major side-effect of recombinant human Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the long-term continuous delivery of Epo in both normal and uremic rats.

DOI： 10.1038/sj.gt.3301412

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Background. Sustained proteinuria is reported to be very harmful to the tubulointerstitium, leading to severe interstitial injury. However, it remains unclear whether sustained proteinuria itself is responsible for severe interstitial injury because, in the previously reported models, the development of factors other than proteinuria in tubulointerstitial lesions could not be excluded completely.
Methods. After treatment to induce immune tolerance to mouse immunoglobulin, 20 rats were injected with anti-rat slit diaphragm monoclonal antibody (mAb) 5-1-6 twice a week for 6 months and were then sacrificed.
Results. mAb 5-1-6 induced massive proteinuria in II rats. In nine rats with mild proteinuria, no histological alteration could be detected with light microscopy and immunofluorescence. In nephrotic rats, light microscopy showed minor glomerular abnormalities, with interstitial oedema, tubular epithelial cell degeneration and interstitial cell infiltration. Immunofluorescence revealed increased expression of vimentin and an increased number of OX1-, OX19- and ED1-positive cells. However, we could not detect any accumulation of type I and IV collagen or laminin in the tubulointerstitium. RT-PCR showed that the expression of mRNA for type I collagen was not increased, compared with that in control rats.
Conclusions. We succeeded in developing a model of persistent nephrosis without severe glomerular abnormalities, nephrectomy or other manoeuvres known to induce disturbed haemodynamics, using an agent without tubulointerstitial toxicity, and considered it to be suitable for investigating the direct toxicity of proteinuria. In this model, isolated massive proteinuria induced interstitial injury. However, the degree of injury was suggested to be much less than that observed in other previously developed models.

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It has been demonstrated that gene transfer by in vivo electroporation of mouse muscle increases the level of gene expression by more than 100-fold over simple plasmid DNA injection. We tested continuous rat erythropoietin (Epo) delivery by this method in normal rats, using plasmid DNA expressing rat Epo (pCAGGS-Epo) as the vector. A pair of electrodes was inserted into the thigh muscles of rat hind limbs and 100 μg of pCAGGS-Epo was injected between the electrodes. Eight 100-V, 50-msec electric pulses were delivered through the electrodes. Each rat was injected with a total of 400 μg of pCAGGS-Epo, which was delivered to the medial and lateral sides of each thigh. The presence of vector-derived Epo mRNA at the DNA injection site was confirmed by RT-PCR. The serum Epo levels peaked at 122.2 ± 33.0 mU/ml on day 7 and gradually decreased to 35.9 ± 18.2 mU/ml on day 32. The hematocrit levels increased continuously, from the preinjection level of 49.5 ± 1.1 to 67.8 ± 2.2% on day 32 (p &lt
0.001). In pCAGGS-Epo treated rats, endogenous Epo secretion was downregulated on day 32. In a control experiment, intramuscular injection of pCAGGS-Epo without subsequent electroporation did not significantly enhance the serum Epo levels. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the continuous delivery of Epo.

DOI： 10.1089/10430340050015897

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.tp.0000543287.07980.0b

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.tp.0000543456.88760.cc

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

(目的)腎移植後の慢性抗体関連型拒絶反応(Chronic antibody mediated rejection;CAMR)に対するボルテゾミブの効果については報告が少なく、今回5症例に使用したためその結果を報告する。(対象と方法)5名の腎移植後CAMR患者に対し、初期治療として血漿交換、ガンマグロブリン静注療法、ステロイドパルス治療、リツキシマブ投与が全例で施行された。初期治療後、抗ドナーHLA抗体が陰性化せず、組織学的にCAMR残存があったため、ボルテゾミブ1.3mg/m2をday1、4、8、11の4回静脈内投与した。ボルテゾミブ投与3ヵ月後に抗HLA抗体検査、6ヵ月後に抗HLA抗体検査と移植腎生検を行い、治療効果を判定した。(結果)ボルテゾミブ投与後の移植腎機能は5例中3例で安定していたが、2例において血清クレアチニン(sCr)の継時的な上昇を認めた。ボルテゾミブ投与により抗HLA class I抗体は有意な減少を示したが、抗HLA class II抗体に関しては経過を通して有意な減少を示さなかった。また、ボルテゾミブ投与による組織学的な改善は認めなかった。移植腎機能が悪化した2症例は、治療前のsCrが高く、組織所見ですでに間質の線維化や尿細管の萎縮が存在した症例であった。(結論)臨床的、組織学的に悪化したCAMRに対し1コースのボルテゾミブ投与は、移植腎機能の安定化に寄与しない。(著者抄録)

DOI： 10.5980/jpnjurol.109.68

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Language：Japanese   Publisher：(一社)日本腎臓学会  

J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

<p> (Backgrounds) The efficacy of bortezomib for chronic antibody mediated rejection (CAMR) after kidney transplantation is still obscure.</p><p> (Materials and methods) CAMR were persisted in 5 recipients who were treated with plasma exchange, low dose of IVIG, steroid pulse therapy, and rituximab. 1.3 mg/m² of bortezomib was administered on days 1, 4, 8, 11. Serum creatinine (sCr) levels, anti-HLA antibodies, and histology were analyzed.</p><p> (Results) Stable sCr levels were obtained in 3 out of 5 recipients. No one lost renal graft function during follow-up periods. Anti-HLA class I antibodies were significantly decreased after bortezomib treatment, however anti-HLA class II antibodies were not changed. Histology showed no improvement at 6 months after bortezomib administration. Two recipients whose sCr levels increased during follow-up had already had interstitial fibrosis and tubular atrophy (IF/TA) in histology before bortezomib treatment.</p><p> (Conclusions) The use of bortezomib after IF/TA could be detected in histology may not contribute to stabilize renal graft function in CAMR.</p>

DOI： 10.5980/jpnjurol.109.68

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DOI： 10.1016/j.juro.2017.02.251

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DOI： 10.1016/j.juro.2017.02.2169

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：長岡赤十字病院  

74歳女。食欲不振を主訴とした。左上顎洞癌(T3N2bM0)に対して60Gy放射線療法とセツキシマブによる化学療法が行われたが、施行後にCre 1.89mg/dl、尿中赤血球50-99/HPF、尿蛋白 (3+)を認め、急速進行性糸球体腎炎症候群を呈した。腎生検では尿細管間質障害と管内細胞増殖、細胞性半月体を伴う膜性増殖性糸球体腎炎を示し、セツキシマブ投与後に急速進行性糸球体腎炎を呈したこと、尿細管間質障害を伴うIgA沈着優位の管内細胞増殖、メサンギウム融解、細胞性半月体を伴うメサンギウム増殖性腎炎の像が既報と類似していたことから、セツキシマブに伴う腎障害と考えられた。ステロイドパルス療法を行い、後療法として経口ステロイドを継続したところ、一時的に尿毒症とアシドーシスが進行して血液透析導入となったものの、腎機能は徐々に改善して血液透析から離脱できた。経口ステロイドを漸減し、現在、Cre 1.70mg/dl前後で経過している。

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Language：Japanese   Publisher：日本臨床腎移植学会  

Pentraxin 3(PTX3)は炎症局所産生性の急性期炎症蛋白で、拒絶反応時に腎間質で発現が増加する。傍尿細管毛細血管のC4d沈着(C4d on PTC)は抗体関連型拒絶反応(ABMR)診断の条件だが、ABO血液型不適合(ABO-I)移植では非特異的に観察される。今回、PTX3発現が、ABO-I移植腎での組織学的ABMRの新規指標となるかを検討した。ABO-I腎移植20例(ABMR発症4例、非発症16例)を対象に、PTX3発現増加およびC4d on PTCによりABMRを診断する場合の感度・特異度を求めた。陽性所見は、PTX3はABMR群3例、非発症群0例、C4d on PTCはABMR群全例と非発症群12例でみられた。診断感度と特異度はそれぞれ、PTX3は75%と100%、C4d on PTCは100%と25%であった。PTX3発現増加は、ABO-IでのABMRの新規組織学的指標になり得ると思われた。(著者抄録)

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経皮的針腎生検(腎生検)は,腎疾患を正しく診断し,適切な治療法の選択と予後の推定のために行う.腎生検は侵襲的検査法のため,合併症の危険性を理解し,腎生検によって得られる情報が患者の利益になるか否かを慎重に検討したうえで施行する.腎生検の適応は検尿異常,腎機能障害などである.腎生検の禁忌は,出血傾向,腎実質内の感染症,萎縮腎などである.光学顕微鏡標本,免疫組織検査(免疫蛍光抗体法,酵素抗体法など),電子顕微鏡標本などから,得られた組織の情報を最大限に引き出して評価する.(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2014246658

Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2014076243

Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本臨床社  

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：新潟県立新発田病院  

症例は56歳女性。8年前に腰痛、IgG 5.0g/dl、IgG-κM蛋白、Cre 4.51mg/dl、尿蛋白(2+)から多発性骨髄腫(MM)、Durie &amp; Salmon stageIIIBと診断。化学療法で寛解しCre 0.42mg/dl、尿蛋白(-)で退院。3年後の骨髄穿刺で完全寛解(CR)判定。IgG 1.6〜2.0g/dl、Cre 0.6〜0.7mg/dl、8年後、IgG 2.6g/dl、尿蛋白(+)を認めたがCre 0.74mg/dl。1ヵ月半後、水様下痢、感冒様症状あり非ステロイド系消炎鎮痛剤(NSAID)を内服、2日後、無尿のため当院受診し7kgの体重増加、Cre 5.87mg/dlから急性腎不全と診断、血液透析に導入された。腎生検では、10個中4個が全節性硬化糸球体であった。尿細管腔内にmyeloma castが多数存在し、骨髄腫腎と診断。骨髄穿刺で多発性骨髄腫、再燃と診断された。血液内科でdexamethasone、bortezomib療法を開始後、自尿は増加したが、Creは正常化しなかった。MMの29%は診断時に腎不全をきたしているが、その58%は1年以内にCreは正常化する。しかし、本例は寛解8年後に骨髄腫腎・急性腎不全にて再発し、新規治療法で原病はコントロールされたが維持透析を要した。文献的考察を加え報告する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：新潟県立病院医学会  

症例1は19歳女性で、15歳時に潰瘍性大腸炎(UC)と診断され、メサラジン、整腸剤で治療され良好に経過した。17歳時に学校検診で血尿を指摘され、uRBC5〜9/hpf、UP0.5g/日で経過観察された。19歳時、uRBC30〜49/hpf、UP0.5g/日と増悪し、経皮的腎生検で入院した。貧血や明らかな腎機能・肝機能障害はなく、血清IgA等、免疫グロブリンや補体価に異常なかった。uRBC10〜19/hpfで赤血球変形が認められた。腎生検で全節性硬化はなかったが、巣状、分節性、軽度のメサンギウム細胞増殖と瀰漫性、全節性、軽度のメサンギウム基質増加が認められた。20%の糸球体に癒着、分節性硬化や半月体の分節性病変を認め、IgA腎症、予後比較的不良群と診断された。食事療法に加え、プレドニゾロン(PSL)を3mgから開始し、以後漸減した。腎機能増悪を認めなかったが、経過中にUCが増悪し、PSL増量、タクロリムス投与でUCは緩解した。症例2は79歳男性で、53歳時にUCと診断され、PSL60mgで加療し緩解したためPSLを中止した。UCは再発し、58〜67歳時にPSL15mg再投与、以後はメサラジンで治療された。79歳時に浮腫、低タンパク血症からネフローゼ症候群と診断され、腎生検のため入院した。糖尿病性網膜症は認めず、明らかな腫瘍性病変はなく、大腸内視鏡でUCは緩解期で、生検でアミロイドーシスを認めず、腎生検所見より膜性腎症ステージ1〜2と診断された。肝炎や悪性腫瘍、薬剤に伴う二次性の膜性腎症は否定的と考え、膜性腎症はステロイドに良好に反応せず、高齢でステロイドの副作用を合併したことや患者の希望でPSLは開始せず、食事療法に加え、ACE阻害薬を開始した。尿タンパクは5〜6g/gCreと持続しているが、アルブミンは3g/dlまで漸増し、浮腫も軽快し、コレステロール値も著明な増悪はみられていない。

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

透析患者の高齢化に伴い、脳血管障害による認知症患者も増加が予想される。認知症の症状は、透析治療において様々な障害になり得るが、認知症があること自体は透析導入の禁忌事項ではない。認知症患者の透析方法の選択には、安全性とQOLを重視しなければならないが、血液透析(HD)か、腹膜透析(PD)かの選択は、医学的な要因に加え社会的要因も考慮する必要がある。1つとして、介護者との綿密な検討が必要である。また、安定した透析維持には、社会支援の利用も不可欠である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

パラプロテインは、免疫グロブリンまたはその構成成分(多くはL鎖)からなり、形質細胞またはB細胞の異常増殖や、慢性炎症などの際に認められる。パラプロテインは骨髄腫腎や糸球体沈着症(GDD)の原因となる。L鎖が沈着する代表例はアミロイドーシスであるが、非アミロイド性のパラプロテインによるGDDは、(1)特徴的な化学的性質を持つ免疫グロブリンが沈着するクリオグロブリン腎症、(2)L鎖(またはH鎖)が沈着するLCDD、HCDD、LHCDD、(3)線維状構造の免疫グロブリンが沈着するimmunotactoid腎症(ITG)の3つに分類される。(著者抄録)

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

軽度二次性副甲状腺機能亢進症に対する静注活性型ビタミンD製剤の治療指針にはコンセンサスがない.92人の血漿intact PTH&lt;300pg/mlの軽度二次性副甲状腺機能亢進症合併透析者がマキサカルシトール2.5μg×3回/週,マキサカルシトール10柊g×1回/週,カルシトリオール0.5μg×2回/週,カルシトリオール1.0μg×1回/週のいずれかのプロトコールに割り付けられ,特別な副作用がなくintact PTH&gt;300pg/mlとなるまでの期間を観察した.マキサカルシトール10μg×1回/週群の維持期間はマキサカルシトール2.5μg×3回/週群に比較して有意に短かった(p&lt;.05)が,カルシトリオール0.5μg×2回/週群とカルシトリオール1.0μg×1回/週群の維持期間に有意差は認められなかった.この結果は両者の血中半減期の違いによって生じるものと思われる.今後は副作用出現頻度も勘案し,活性型ビタミンD静注治療のもっとも好ましいプロトコールを確立させる必要がある(著者抄録)

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Language：Japanese   Publisher：新潟医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2005034667

Language：Japanese   Publisher：(株)日本メディカルセンター  

経口ビタミンD治療に抵抗性の副甲状腺機能亢進症を併発した透析患者に,マキシカルシトール間欠的大量静注療法を行う前向き研究を行った.マキサカルシトール治療に伴って,intact PTHは時間依存性に低下した.bAPも速やかに低下した.intact OCは一過性に上昇した後に低下傾向を示した.血清カルシウム濃度は明らかに上昇した.リン濃度は変わらなかった.高カルシウム血症,痒み以外の明らかな副作用は認められなかった

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese  

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Other Link： http://search.jamas.or.jp/link/ui/2002181403

Language：Japanese   Publisher：新潟医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2002166166

Language：Japanese   Publisher：(一社)日本人工臓器学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2002001648

Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本アフェレシス学会  

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Other Link： http://id.nii.ac.jp/1141/00149716/

Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：鳥居薬品(株)  

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