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

INTRODUCTION: We investigated whether N-terminal and C-terminal products of expressed in renal cell carcinoma/mesothelin (N-ERC and C-ERC) in peritoneal effluent can predict peritoneal permeability in patients undergoing peritoneal dialysis (PD). METHODS: Thirty-seven peritoneal effluent samples were obtained from 26 PD patients. High transport status was determined by the peritoneal equilibration test as a dialysate/plasma ratio of creatinine (D/P Cr) ≥ 0.81. Effluent cancer antigen 125 (CA125) was used as a reference. RESULTS: Effluent N-ERC concentration was better correlated with D/P Cr than effluent C-ERC or CA125 concentration. In multivariate analyses, effluent N-ERC and C-ERC, but not CA125, were significant predictors of high transport status after adjusting for age, PD duration, and residual renal Kt/V. ROC analysis showed that effluent N-ERC was the best predictor of high transport status among those three biomarkers. CONCLUSION: Effluent N-ERC predicts increased peritoneal permeability in patients undergoing PD.

DOI： 10.1111/1744-9987.13786

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

<title>Abstract</title>Long-term infection of the stomach with <italic>Helicobacter pylori</italic> can cause gastric cancer. However, the mechanisms by which the bacteria adapt to the stomach environment are poorly understood. Here, we show that a small non-coding RNA of <italic>H. pylori</italic> (HPnc4160, also known as IsoB or NikS) regulates the pathogen’s adaptation to the host environment as well as bacterial oncoprotein production. In a rodent model of <italic>H. pylori</italic> infection, the genomes of bacteria isolated from the stomach possess an increased number of T-repeats upstream of the HPnc4160-coding region, and this leads to reduced HPnc4160 expression. We use RNA-seq and iTRAQ analyses to identify eight targets of HPnc4160, including genes encoding outer membrane proteins and oncoprotein CagA. Mutant strains with HPnc4160 deficiency display increased colonization ability of the mouse stomach, in comparison with the wild-type strain. Furthermore, HPnc4160 expression is lower in clinical isolates from gastric cancer patients than in isolates derived from non-cancer patients, while the expression of HPnc4160’s targets is higher in the isolates from gastric cancer patients. Therefore, the small RNA HPnc4160 regulates <italic>H. pylori</italic> adaptation to the host environment and, potentially, gastric carcinogenesis.

File： Kinoshita et al_Small RNA regulates H.pylori adaptation_Nat Commun2021.pdf

DOI： 10.1038/s41467-021-22317-7

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/j.kint.2021.03.034

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/cpt.2275

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/bcp.14807

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Objectives</title>
ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood.


</sec>
<sec>
<title>Methods</title>
We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: &amp;lt;65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative).


</sec>
<sec>
<title>Results</title>
A total of 1338 patients with AAV were included: 66% had disease onset at &amp;lt;65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03].


</sec>
<sec>
<title>Conclusion</title>
Within 6 months of diagnosis of AAV, patients &amp;gt;65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.


</sec>

File： Monti et al_DCVAS_Rheumatology2021.pdf

DOI： 10.1093/rheumatology/keaa215

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once-weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty-six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low-UF (<mean - 1SD), middle-UF (≥mean - 1SD and <mean + 1SD), and high-UF (≥mean + 1SD). High-UF group showed larger extracellular water normalized to height (P = .038) and longer HD sessions (P < .001) compared with low-UF group, whereas low-UF group was older than middle-UF group (P = .001). Technique survival rate was significantly lower in high-UF group than in low and middle-UF groups (P < .001), and the rates at 44 months were 80%, 90%, 20% in low, middle, and high-UF groups, respectively. Chronic overhydration was the leading cause of technique failure for all. This study suggests that fluid overload remains a major cause of technique failure of PD even after once-weekly HD is added.

DOI： 10.1111/1744-9987.13509

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/bcp.14749

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is an alternative dialysis method for patients with end-stage kidney disease (ESKD). The complementary use of once-weekly HD expedites to achieve adequate dialysis and enables to prolong PD duration. Although PD+HD has been widely employed among Japanese PD patients, it is much less common outside Japan. Clinical evidences are still not enough, especially in long-term prognosis and appropriate treatment duration, suitable patients, and generalizability. A retrospective cohort study by Chung et al. (BMC Nephrol 21:348, 2020) compared the risk of mortality and hospitalization between PD patients who were transferred to PD+HD and those who were transferred to HD in Taiwan. Because the mortality and hospitalization rates did not differ between the groups, the authors concluded that, PD+HD may be a rational and cost-effective treatment option. It should be noted that the effects of PD+HD on long-term prognosis are still unknown due to too-short PD+HD duration. However, the study identified the high-risk patient population and showed the generalizability of PD+HD. PD+HD is a treatment of choice in patients with ESKD who prefer PD lifestyles even after decline in residual kidney function.

File： Tanaka and Mise_ commentary_BMC Nephrol2021.pdf

DOI： 10.1186/s12882-020-02212-x

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

The Pharmaceuticals and Medical Devices Agency (PMDA) have approved hundreds of new drugs in recent years. We retrospectively analyzed the new drugs approved in Japan from 2008 to 2019, and identify the first-in-world approvals and clarify the current drug lag. The new drug and the drug lag were defined as a drug with a new active substance and a difference between the approval date in Japan and the international birth date, respectively. Among 400 new drugs approved in Japan during the last 12 years, 80 (20.0%) were first approved in Japan, and 320 were outside Japan (the United States: 202, 50.5%; Europe: 82, 20.5%; other regions: 36, 9.0%). Of these, 45 new drugs have not yet been approved outside Japan, and the remaining 355 have been globally approved in Japan and overseas. The number of new drug approvals were the largest in oncology followed by metabolic/endocrine and infectious diseases. The median drug lags (year) among all 400 new drugs and 355 new drugs with global approvals were 4.3 and 4.7 in the 1st tertile (2008-2011), 1.5 and 2.6 in the 2nd tertile (2012-2015), and reduced to 1.3 and 2.2 in the 3rd tertile (2016-2019), respectively. Substantial drug lag remains in neurology, psychiatry, and therapeutic areas where the number of new drug approvals was relatively small. Collectively, one-fifth of the new drugs approved in Japan are first-in-world approvals. Drug lag has been greatly decreased, although it still exists.

File： Tanaka et al_400NAS_Clin Pharmacol Ther2020.pdf

DOI： 10.1002/cpt.2080

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

Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

File： Kidney failure clinical trial outcome definitions_A Levin et al_KI2020.pdf

DOI： 10.1016/j.kint.2020.07.013

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：American Society of Nephrology (ASN)  

File： Tanaka M, et al_Role of Roxadustat for ESA-Resistant Renal Anemia —Read with Caution_letter_JASN2020.pdf

DOI： 10.1681/asn.2020060821

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross-sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre-HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post-HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre-HD (β = -0.8, P = 0.03) and similar to PD (β = -0.5, P = 0.24) and post-HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre-HD, but not in PD and post-HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.

DOI： 10.1111/1744-9987.13444

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

Helicobacter pylori, a pathogenic bacterium that colonizes in the human stomach, harbors DNA repair genes to counter the gastric environment during chronic infection. In addition, H. pylori adapts to the host environment by undergoing antigenic phase variation caused by genomic mutations. The emergence of mutations in nucleotide sequences is one of the major factors underlying drug resistance and genetic diversity in bacteria. However, it is not clear how DNA repair genes contribute to driving the genetic change of H. pylori during chronic infection. To elucidate the physiological roles of DNA repair genes, we generated DNA repair-deficient strains of H. pylori (ΔuvrA, ΔuvrB, ΔruvA, Δnth, ΔmutY, ΔmutS, and Δung). We performed susceptibility testing to rifampicin in vitro and found that ΔmutY exhibited the highest mutation frequency among the mutants. The number of bacteria colonizing the stomach was significantly lower with ΔmutY strain compared with wild-type strains in a Mongolian gerbil model of H. pylori infection. Furthermore, we performed a genomic sequence analysis of the strains isolated from the Mongolian gerbil stomachs eight weeks after infection. We found that the isolated ΔmutY strains exhibited a high frequency of spontaneous G:C to T:A mutations. However, the frequency of phase variations in the ΔmutY strain was almost similar to the wild-type strain. These results suggest that MutY may play a role in modes of gastric environmental adaptation distinct from phase variation.

DOI： 10.1016/j.bbrc.2020.02.087

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Introduction: Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used for PD patients with decreased residual kidney function in Japan; however, hospitalization for this combined dialysis has not been investigated so far. We compared the risk of hospitalization for PD+HD with that for HD.
Methods: A multicenter, prospective observational study was conducted on 42 PD+HD and 42 HD patients matched for age and diabetic nephropathy. The main outcome measure was the cumulative incidence of hospitalization for any cause assessed with the Kaplan-Meier method. Hospitalization rates (the number of admissions per 100 patient-years) associated with dialysis modality were also calculated. The impact of dialysis modality on time to hospitalization was analyzed using the Cox proportional hazard model.
Results: There was no significant difference between groups in terms of age, sex, dialysis vintage, diabetic nephropathy, and comorbidities. The cumulative incidence of hospitalization did not significantly differ between the groups (log-rank test, P = 0.36). Although total hospitalization rates were 66.0 in PD+HD and 59.2 in HD, hospitalization rates for the sum of PD-related infections (a composite of catheter-related infection and peritonitis) and vascular access troubles were 21.7 in PD+HD and 7.2 in HD. On univariate Cox proportional hazard analysis, dialysis modality had no significant impact on time to hospitalization.
Conclusion: The risk of hospitalization was not significantly different between PD+HD and HD, although PD+HD patients had a higher risk of dialysis access-related complications than HD patients.

File： Tanaka M, et al. Hospitalization for PD+HD Versus HD_KI rep2020.pdf

DOI： 10.1016/j.ekir.2020.01.004

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.

File： Tanaka M, et al. GAS_SciRep2020.pdf

DOI： 10.1038/s41598-020-60306-w

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Other Link： http://www.nature.com/articles/s41598-020-60306-w

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

Background: The health-related quality of life (HRQOL) of dialysis patients has not been well examined, especially in combination therapy with peritoneal dialysis and hemodialysis (PD+HD) patients. We compared the HRQOL of PD+HD patients with that of HD and PD patients.
Methods: A multicenter, cross-sectional study was conducted on 36 PD+HD, 103 HD, and 90 PD patients in Japan who completed the Kidney Disease Quality of Life Short Form 36, version 1.3. HRQOL scores were summarized into physical- (PCS), mental- (MCS), role/social- (RCS), and kidney disease component summaries (KDCS).
Results: Of the PD+HD patients, 31 (86%) transferred from PD and 5 (14%) transferred from HD. They had the longest dialysis vintage and the smallest urine volume. PCS, MCS, and KDCS HRQOL scores of PD+HD patients were comparable with those of HD and PD patients. However, the RCS score for PD+HD was significantly higher than that for HD (p = 0.020) and comparable with that for PD. PD+HD and PD were associated with significantly higher RCS scores than HD after adjusting for age, gender, diabetic nephropathy, dialysis vintage, ischemic heart disease, and peripheral arterial disease.
Conclusions: For RCS, HRQOL in PD+HD patients was better than that in HD and comparable with that in PD patients, whereas the PCS, MCS, and KDCS HRQOL scores of PD+HD patients were comparable with those of HD and PD patients.

DOI： 10.1177/0896860819894066

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：American Society of Nephrology (ASN)  

File： Tanaka M, et al_ESA resistance may be a potential confounder for mortality among different ESA types_JASN2020.pdf

DOI： 10.1681/asn.2019060556

DOI： 10.1681/ASN.2019060556

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

Background: The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes.
Methods: This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%.
Discussion: This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients.

File： Niikura R, Tanaka M, et al. Trials2018.pdf

DOI： 10.1186/s13063-018-2558-y

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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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Open Access Text Pvt, Ltd.  

File： Yamada D, Tanaka M, et al. Naftpidil protocol_Prev Med Commun Health2018.pdf

DOI： 10.15761/pmch.1000106

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Language：Japanese  

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

Peritonitis remains an important cause of morbidity and mortality in peritoneal dialysis (PD) patients, but its incidence and the distribution of causative organisms vary widely between institutions and age groups. This study was performed to investigate the recent status and risk factors of PD-related peritonitis and to clarify differences between age groups. We retrospectively reviewed the medical records of 119 PD patients treated at our department between January 2002 and January 2013. We calculated both overall and organism-specific peritonitis rates and also analyzed risk factors. Sixty-three episodes of peritonitis occurred during 261.5 patient-years for an incident rate of 0.24 episodes/patient-year. Multivariate analysis showed that older age (≥65 years) and hypoalbuminemia (<3.0 g/dL) were associated with an increased risk of peritonitis (P = 0.035 and P = 0.029, respectively). In elderly patients (≥65 years old), the rate of peritonitis due to Gram-positive and Gram-negative bacteria was 0.17 and 0.08 episodes/patient-year, respectively, and Gram-positive peritonitis was markedly more frequent than in younger patients (<65 years old). In particular, there was a high frequency of Staphylococcus aureus peritonitis in elderly patients (0.09 episodes/patient-year) and it had a poor outcome. At our department, the risk of peritonitis was increased in older patients and patients with hypoalbuminemia. The distribution of causative organisms was markedly different between age groups and analysis of organism-specific peritonitis rates helped to identify current problems with our PD program.

DOI： 10.1111/1744-9987.12449

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ebiom.2016.07.012

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

Small-vessel vasculitis is a life-threatening autoimmune disease that is frequently associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Conventional immunotherapy including steroids and cyclophosphamide can cause serious adverse events, limiting the efficacy and safety of treatment. Eicosapentaenoic acid (EPA), a key component of fish oil, is an omega-3 polyunsaturated fatty acid widely known to be cardioprotective and beneficial for vascular function. We report two elderly patients with systemic ANCA-associated vasculitis (AAV) in whom the administration of EPA in concert with steroids safely induced and maintained remission, without the use of additioal immunosuppressants. To explore the mechanisms by which EPA enhances the treatment of AAV, we employed SCG/Kj mice as a spontaneous murine model of AAV. Dietary enrichment with EPA significantly delayed the onset of crescentic glomerulonephritis and prolonged the overall survival. EPA-derived anti-inflammatory lipid mediators and their precursors were present in the kidney, plasma, spleen, and lungs in the EPA-treated mice. Furthermore, a decrease in ANCA production and CD4/CD8-double negative T cells, and an increase in Foxp3(+) regulatory T cells in the lymph nodes of the kidney were observed in the EPA-treated mice. These clinical and experimental observations suggest that EPA can safely support and augment conventional therapy for treating autoimmune small-vessel vasculitis.

File： Hirahashi J, Tanaka M, et al. EPA for small-vessel vasculitis. Sci Rep2014.pdf

DOI： 10.1038/srep06406

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Other Link： http://www.nature.com/articles/srep06406

Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Background: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown.
Methods: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS.
Results: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3).
Conclusions: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

DOI： 10.1159/000381938

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

Background: Cardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution.
Methods: This retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years.
Results: Of 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan-Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p=0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event.
Conclusions: Peritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.

File： Hamasaki Y, Tanaka M, et al. CV risk and peritoneal permeability BMC Nephrol2014.pdf

DOI： 10.1186/1471-2369-15-173

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

The acute onset of idiopathic nephrotic syndrome (NS) is often accompanied by acute kidney injury, which can lead to congestive heart failure and lung edema. In this report, we present two cases of NS-induced acute kidney injury successfully treated with a low dose of carperitide, a human atrial natriuretic peptide. In combination with standard diuretic therapy and immunotherapy, carperitide retained the renal function and spared the need for renal replacement therapy, including hemodialysis. Although further investigation in clinical trials is required to validate these findings, carperitide may be useful for maintaining the renal function in cases of NS-induced acute kidney injury.

DOI： 10.2169/internalmedicine.53.1724

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

DOI： 10.3747/pdi.2012.00212

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Publishing type：Research paper (scientific journal)   Publisher：Dustri-Verlgag Dr. Karl Feistle  

A 44-year-old man with a 17-year history of Crohn's disease (CD) was referred to our nephrology department on suspicion of drug-induced nephrotoxicity. Over the preceding 18 months, he had slowly progressive renal insufficiency with slight urinary abnormalities. His disease activity had been well controlled up to that point with 5-aminosalicylic acid and azathiopurine. Laboratory examination revealed slight proteinuria without hematuria and an elevated serum creatinine level of 1.4 mg/dl. Pathological examination revealed amyloid A (AA) deposition in the kidney, predominantly in the arterial and arteriolar walls with little to none in the glomerular capillaries. AA amyloidosis is typically accompanied by glomerular amyloid deposition and massive proteinuria. In the present case, however, vascular amyloid deposition was predominant, and the renal function was deteriorated with slight urinary abnormalities. The present case confirmed the importance of conducting a definitive pathological diagnosis of renal insufficiency in CD patients.

DOI： 10.5414/cn107151

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

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1440-1797.2012.01609.x

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

DOI： 10.3747/pdi.2011.00301

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1744-9987.2011.01041.x

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

File： Kurita N, Tanaka M, et al. Glomerular light chain in Myeloma case. KI2011.pdf

DOI： 10.1038/ki.2011.342

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

We report the case of a 53-year-old hemodialysis patient with severe aortic stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula (AVF) construction. He presented with hypotension and repeated syncope soon after distal radiocephalic AVF construction, and finally developed a respiratory arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent aortic valve replacement surgery. In the present case, the heart with severe aortic stenosis could not increase cardiac output in response to the reduction in peripheral vascular resistance caused by the AVF. High-output heart failure, a relatively rare AVF-associated disorder, occurs with an excessive AVF flow, usually more than 3 L/min or 30% of cardiac output. However, heart failure may develop soon after construction of an AVF with a moderate blood flow if a patient's cardiac function is severely impaired. In addition, heart failure may improve with AVF preservation if the underlying heart disease is treatable.

DOI： 10.1007/s10157-011-0484-3

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

DOI： 10.3747/pdi.2010.00273

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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   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/naika.100.1044

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Other Link： https://jlc.jst.go.jp/DN/JALC/00368341166?from=CiNii

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Arteriovenous dialysis access may impose a burden on the cardiac system. The objective of this study is to examine the usefulness of access closure in hemodialysis patients with refractory heart failure and to identify possible factors associated with symptomatic improvements. The study population comprised 33 hemodialysis patients with symptomatic heart failure (New York Heart Association [NYHA] class ≥ II), who underwent arteriovenous access closure (30 fistulas and three grafts) between 1991 and 2008. In all patients, heart failure was refractory to all possible medical and surgical treatments, and persisted after optimal dry weight control. First, short-term changes in hemodynamics, clinical symptoms and echocardiographic morphology were examined. Second, clinical and echocardiographic parameters were compared between responders (N=23), who demonstrated NYHA class improvement after access closure, and non-responders (N=10). After access closure, systolic blood pressure rose and the heart rate decreased significantly. Body weight and echocardiographic parameters did not change significantly. Twenty-three patients (70%) demonstrated NYHA class improvement and were designated as responders. In responders, the duration from access creation to closure was significantly shorter and fewer had ischemic heart disease, compared with non-responders. Access flow, cardiac output and ejection fraction were comparable between the two groups. Although the five-year survival was 20.2% in all patients, responders showed better early survival than non-responders. Arteriovenous access closure improved clinical symptoms in 70% of patients with refractory heart failure. This improvement was especially likely to be achieved in patients without ischemic heart disease and those who developed heart failure within a relatively short time after access creation.

DOI： 10.1111/j.1744-9987.2010.00907.x

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

Predominant or codominant immunoglobulin (Ig) A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN). Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.

File： Tanaka M, Seki G, et al. IgAN Review. ClinDevImmunol2011.pdf

DOI： 10.1155/2011/470803

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Other Link： http://downloads.hindawi.com/journals/jir/2011/470803.xml

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We report a case of a 47-year-old man with multicentric Castleman's disease (MCD) and progressive renal dysfunction due to mesangial proliferative glomerulonephritis, possibly from IgA nephropathy. At age 36 years, he was referred to a hematologist due to hypergammaglobulinemia. Because of systemic lymph node swelling, he underwent right cervical lymph node biopsy at age 41 years and MCD (plasma cell type)was diagnosed. During this period, microscopic hematuria and persistent proteinuria occurred and his renal function deteriorated (serum creatinine (Cr) rising from 0.7 mg/dL to 1.4 mg/dL). Treatment with intravenous methylprednisolone at the dose of 1 g daily for 3 days followed by oral prednisolone at 20 mg daily reduced his lymphadenopathy and improved the renal function. However, his renal function deteriorated again, from Cr 0.8 mg/dL to 1.8 mg/dL over 6 years in line with gradual prednisolone tapering to 6 mg daily. At age 47 years, he was referred to our nephrology department and underwent a renal biopsy. The microscopic examination showed IgA nephropathy with crescent formation, accompanied by mild lymphoplasmacytic tubulointerstitial nephritis. Treatment with the same dose of intravenous methylprednisolone therapy followed by oral prednisolone at 40 mg daily, improved his proteinuria, hematuria and renal dysfunction. The coexistence of MCD and IgA nephropathy is a rare phenomenon. In addition, IL-6, overproduced by MCD might have influenced the mesangial cell proliferation and the activity of IgA nephropathy in the present case.

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Language：Japanese   Publisher：The Japanese Society for Dialysis Therapy  

A 34-year-old male with end-stage renal failure due to type1 diabetes started peritoneal dialysis (PD) via a double-cuffed Tenckhoff catheter in April 2008. He was using a double-bag system with manual connectology and underwent nocturnal intermittent PD. In January 2009, he developed his first episode of peritonitis, presenting with slight fever, abdominal pain, diarrhea, vomiting and cloudy dialysate. Physical examination demonstrated abdominal rebound tenderness. Drained dialysate was cloudy with an elevated cell count of 2,500/μL (96% polymorphonuclear leukocytes). He was admitted to the hospital and successfully treated with 8 days of intraperitoneal or intravenous cefazolin and ceftazidime, followed by oral cefotiam for 6 days. There was no recurrence of peritonitis thereafter. Neisseria subflava was isolated from the dialysate and was identified as the pathogen causing peritonitis. <I>Neisseria subflava</I> is commensal in the upper respiratory tract, but may rarely cause infections, such as endocarditis and meningitis. A few cases of <I>Neisseria peritonitis</I> have been reported in PD patients, even in those without concomitant diseases. In the present case, contamination by a droplet from the mouth was considered the most probable cause of peritonitis, because the patient did not wear a mask during bag exchanges. The importance of wearing a mask for infection control during PD bag exchanges was reconfirmed.

DOI： 10.4009/jsdt.44.319

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

We report a case of Churg-Strauss syndrome coexistent with coronary vasospasm and pauci-immune necrotizing crescentic glomerulonephritis. A 54-year-old man with bronchial asthma and allergic rhinitis was admitted to our hospital because of acute coronary syndrome. Angiography showed diffuse coronary artery spasm without anatomic stenosis. Acute coronary syndrome due to vasospasm was diagnosed. However, subsequent administration of vasodilators did not suppress angina symptoms. In addition, marked eosinophilia, eosinophilic pneumonitis, chronic sinusitis, pericardial effusion, and slight hematuria with red blood cell casts were detected. Although kidney function was normal, a kidney biopsy showed necrotizing crescentic glomerulonephritis with eosinophilic infiltration in both glomeruli and interstitium. With the diagnosis of Churg-Strauss syndrome, oral prednisolone at a dose of 60 mg/d was administered. Cardiac symptoms, pulmonary and sinonasal lesions, pericardial effusion, and urine sediment resolved rapidly. Six months later, a repeated kidney biopsy showed remarkable improvement and no eosinophilic infiltration. Coronary vasospasm with eosinophilia might be refractory to vasodilators and sensitive to corticosteroid therapy and often has been related to Churg-Strauss syndrome. Slight abnormalities in urine sediment can be the clue to the diagnosis of severe kidney involvement of Churg-Strauss syndrome.

DOI： 10.1053/j.ajkd.2010.03.011

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We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m(2) and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN.

DOI： 10.1007/s00467-010-1568-0

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Publishing type：Research paper (scientific journal)  

Objective: Familiar Mediterranean Fever (FMF) is common among Mediterranean populations, while other populations are rarely affected. The aim of this study was to assess the involvement of MEFV gene mutations among Japanese rheumatoid arthritis patients with or without amyloid A (AA) amyloidosis.

Methods: The frequency of the MEFV mutations, which were identified in Japanese FMF patients, was determined in 126 Japanese RA patients and 76 Japanese healthy subjects.

Results: The M694I mutation was not observed among RA patients and healthy subjects. Allele frequency of R408Q, P369S, E148Q, L110P mutations account respectively for 3.3%, 3.9%, 23.7%, 9.2% in healthy subjects and 5.6%, 6.7%, 24.2%, 9.5% in RA patients. The overall mutation rate was comparable between the RA patients and healthy subjects, as well as between the RA patients with and without amyloidosis.

Conclusion: This study shows the high prevalence of mutations of the MEFV genes in Japanese RA patients. However, our data suggest that the MEFV gene mutations may not be a genetic factor affecting the susceptibility of RA or the development of amyloidosis in a Japanese population.

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Familial Mediterranean fever (FMF) is a hereditary syndrome characterized by recurrent episodes of fever and serositis. In this report, we describe a Japanese patient with FMF and Sjögren's syndrome, in whom acute elevations of transaminase occurred. The histological findings from the liver biopsy specimens demonstrated a nonspecific hepatitis, with liver cell necrosis and interlobular inflammatory cell invasion, without the presence of interface hepatitis or bile duct injury. This case underscores the possibility that MEFV mutations contribute to hepatic inflammation, as seen in this case, by way of an alteration of the pyrin function.

DOI： 10.1111/j.1478-3231.2007.01598.x

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Total pages：x, 468p   Language：Japanese

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Total pages：249p   Language：Japanese

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Total pages：31, 560p   Language：Japanese

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

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

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Language：Japanese   Publisher：臨床体液研究会  

62歳男。虚血性心疾患(3枝病変)に対し冠動脈バイパス術を施行後、経皮的冠動脈形成術を2回施行した。血漿レニン活性(PRA)、血漿アルドステロン(PAC)が高値で、二次性高血圧を疑われていた。気管支炎を契機に心不全が増悪し緊急入院となった。BNPは著明高値で、心陰影拡大と肺うっ血を認めた。心工コーでは左室収縮能が低下していた。軽度腎機能障害と低K血症とともに、PRAとPACが高値であったため、腎動脈狭窄症を疑った。腎動脈造影にて左腎動脈入口部に99%狭窄病変を確認した。血管造影上70%以上狭窄を有し、進行性、治療抵抗性高血圧症を呈しているため、経皮的腎動脈形成術(PTRA)を施行した。PTRA後、収縮期血圧は110mmHgまで下降し、低K血症、心磯能ともに改善、BNPは低下し、心不全症状も軽快した。

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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  

血液透析が循環に及ぼす影響の二つの側面は,一つは動静脈を短絡するバスキュラー・アクセス(VA)が心機能に及ぼす影響であり,もう一つは除水を中心とする透析処置そのものである.VAの作製と修復に関しては,患者の心機能に応じて,内シャントやシャントグラフトの選択の是非を判断する必要がある.時に,シャント血流の遮断とVAの変更を考慮する必要がある.心機能障害のある患者で,丸2日蓄積した体液量を4時間で除去する治療が安全であるためには,食事管理の正確性が求められる.基礎疾患の治療など心機能保持の治療とともに,透析方法の評価と選択,通院の介助などの考慮が必要である.(著者抄録)

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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