Publications by authors named "Shoichi Maruyama"

270 Publications

All-cause and cardiovascular mortality in patients undergoing hemodialysis with aortic sclerosis and mild-to-moderate aortic stenosis: A cohort study.

Atherosclerosis 2021 Jun 25;331:12-19. Epub 2021 Jun 25.

Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address:

Background And Aims: Mild-to-moderate aortic stenosis (AS) and aortic sclerosis, a precursor of AS, are associated with mortality in the general population; however, their association in patients undergoing hemodialysis with higher morbidity of AS is unknown. Thus, we investigated the mortality of aortic sclerosis and mild-to-moderate AS in patients undergoing hemodialysis.

Methods: This was a retrospective multicenter cohort study of consecutive patients undergoing hemodialysis at nine dialysis facilities who underwent screening echocardiography between January 2008 and December 2019. We investigated the mortality of patients with aortic sclerosis or mild-to-moderate AS using multivariable Cox proportional hazards regression.

Results: Among 1,878 patients undergoing hemodialysis, those with normal aortic valves, aortic sclerosis, mild AS, moderate AS, severe AS, and prosthetic aortic valves were 844 (45%), 793 (42%), 161 (8.6%), 38 (2.0%), 11 (0.6%), and 31 (1.7%), respectively. After excluding patients with severe AS and prosthetic aortic valves, we performed comparative analysis on 1,836 patients (mean age, 67 years; 66% male). In a median follow-up of 3.6 years, crude death rates (per 100 person-years) were 5.2, 10.6, and 13.0 in patients with normal aortic valves, aortic sclerosis, and mild-to-moderate AS, respectively. Compared with normal aortic valves, both aortic sclerosis and mild-to-moderate AS were associated with all-cause and cardiovascular death: adjusted hazard ratios (95% confidence intervals) were 1.36 (1.13-1.65) and 1.36 (1.02-1.80) for all-cause death; and 1.52 (1.06-2.17) and 1.74 (1.04-2.92) for cardiovascular death, respectively.

Conclusions: Aortic sclerosis and mild-to-moderate AS were independent risk factors for all-cause and cardiovascular death in patients undergoing hemodialysis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.910DOI Listing
June 2021

Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.

Int Immunol 2021 Jul;33(8):435-446

Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.
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http://dx.doi.org/10.1093/intimm/dxab027DOI Listing
July 2021

Dietary Supplementation With Eicosapentaenoic Acid Inhibits Plasma Cell Differentiation and Attenuates Lupus Autoimmunity.

Front Immunol 2021 15;12:650856. Epub 2021 Jun 15.

Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.

Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. To determine whether the fatty acid composition of diet modulates leukocyte function and the development of systemic lupus erythematosus, we examined the effect of eicosapentaenoic acid (EPA) on the pathology of lupus in drug-induced and spontaneous mouse models. We found that dietary EPA supplementation ameliorated representative lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of lupus.
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http://dx.doi.org/10.3389/fimmu.2021.650856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240640PMC
June 2021

X-chromosome inactivation patterns in females with Fabry disease examined by both ultra-deep RNA sequencing and methylation-dependent assay.

Clin Exp Nephrol 2021 Jun 14. Epub 2021 Jun 14.

Department of Nephrology, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Previous studies examined this correlation using the classical methylation-dependent method; however, conflicting results were obtained. This study was established to ascertain the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes.

Methods: We present five female patients from one family and four individual female patients with Fabry disease. In all cases, heterozygous pathogenic variants in the GLA gene were detected. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing. Fabry Stabilization Index was used to determine the clinical severity.

Results: Skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with low ⍺-galactosidase A activity. In the remaining cases, no skewing was observed, even in the case with the highest total severity score (99.2%).

Conclusion: We conclude that skewed XCI could not explain the severity of female Fabry disease and is not the main factor in the onset of various clinical symptoms in females with Fabry disease.
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http://dx.doi.org/10.1007/s10157-021-02099-4DOI Listing
June 2021

Favorable therapeutic efficacy of low-density lipoprotein apheresis for nephrotic syndrome with impaired renal function.

Ther Apher Dial 2021 May 31. Epub 2021 May 31.

Department of Medicine, Diabetes Center, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m ), and severely impaired (S) (<30 ml/min/1.73 m ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m .
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http://dx.doi.org/10.1111/1744-9987.13694DOI Listing
May 2021

Impact of serum magnesium and bone mineral density on systemic fractures in chronic hemodialysis patients.

PLoS One 2021 20;16(5):e0251912. Epub 2021 May 20.

Department of Nephrology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan.

Introduction: Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) can be used to predict fractures, but its clinical utility has not been fully established in chronic kidney disease (CKD) patients. Magnesium is an essential trace element. Although magnesium is associated with the risk of fractures in non-CKD populations, the relationship is unknown in CKD patients.

Methods: BMD and serum magnesium levels were measured in 358 stable outpatients undergoing maintenance hemodialysis therapy. The primary outcome was fragility fracture. Patients were divided into groups according to the median level of magnesium and the normal threshold value of lumbar spine BMD.

Results: During the median follow-up period of 36 months, 36 (10.0%) fractures occurred. The cumulative incidence rates of fractures were 17.6% and 5.2% [adjusted hazard ratio (aHR) 2.31, 95% confidence interval (CI) 1.03-5.17, P = 0.030] in the lower (<2.6 mg/dL) and higher (≥2.6 mg/dL) magnesium (Mg) groups, respectively, and 21.2% and 7.3% (aHR 2.59, 95% CI 1.09-6.16, P = 0.027) in the low- and high-BMD groups, respectively. The lower-Mg and low-BMD group had a 9.21-fold higher risk of fractures (95% CI; 2.35-47.00; P = 0.0010) than the higher-Mg and high-BMD group. Furthermore, adding both magnesium levels and lumbar spine BMD levels to the established risk factors significantly improved the prediction of fractures (C-index: 0.784 to 0.830, p = 0.041).

Discussion/conclusions: The combination of serum magnesium and lumbar spine BMD can be used for fracture risk stratification and synergistically improves the prediction of fractures in CKD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251912PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136656PMC
May 2021

Low-GDP, pH-neutral solutions preserve peritoneal endothelial glycocalyx during long-term peritoneal dialysis.

Clin Exp Nephrol 2021 May 17. Epub 2021 May 17.

Department of Nephrology and Rheumatology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.

Background: During peritoneal dialysis (PD), solute transport and ultrafiltration are mainly achieved by the peritoneal blood vasculature. Glycocalyx lies on the surface of endothelial cells and plays a role in vascular permeability. Low-glucose degradation product (GDP), pH-neutral PD solutions reportedly offer higher biocompatibility and lead to less peritoneal injury. However, the effects on the vasculature have not been clarified.

Methods: Peritoneal tissues from 11 patients treated with conventional acidic solutions (acidic group) and 11 patients treated with low-GDP, pH-neutral solutions (neutral group) were examined. Control tissues were acquired from 5 healthy donors of kidney transplants (control group). CD31 and ratio of luminal diameter to vessel diameter (L/V ratio) were evaluated to identify endothelial cells and vasculopathy, respectively. Immunostaining for heparan sulfate (HS) domains and Ulex europaeus agglutinin-1 (UEA-1) binding was performed to assess sulfated glycosaminoglycans and the fucose-containing sugar chain of glycocalyx.

Results: Compared with the acidic group, the neutral group showed higher CD31 positivity. L/V ratio was significantly higher in the neutral group, suggesting less progression of vasculopathy. Both HS expression and UEA-1 binding were higher in the neutral group, whereas HS expression was markedly more preserved than UEA-1 binding in the acidic group. In vessels with low L/V ratio, which were found only in the acidic group, HS expression and UEA-1 binding were diminished, suggesting a loss of glycocalyx.

Conclusion: Peritoneal endothelial glycocalyx was more preserved in patients treated with low-GDP, pH-neutral solution. The use of low-GDP, pH-neutral solutions could help to protect peritoneal vascular structures and functions.
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http://dx.doi.org/10.1007/s10157-021-02078-9DOI Listing
May 2021

Factors predicting decline in renal function and kidney volume growth in autosomal dominant polycystic kidney disease: a prospective cohort study (Japanese Polycystic Kidney Disease registry: J-PKD).

Clin Exp Nephrol 2021 Apr 29. Epub 2021 Apr 29.

Department of Advanced Informatics for Genetic Disease, Juntendo University, Tokyo, Japan.

Background: Factors affecting decline in renal function and cyst growth in patients with autosomal polycystic kidney disease (ADPKD) are not fully described, particularly in Japan.

Methods: This was the first multi-facility, prospective, observational cohort study conducted in ADPKD patients at 14 centers in Japan. Patients in the J-PKD registry were assessed from December 2009 to June 2012 (follow-up until June 2017). Patients' data including estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were assessed initially and a maximum of five times annually. Contributing factors to eGFR decline and TKV growth were identified using multiple linear regression analysis.

Results: Of the 340 patients in the J-PKD registry, data analysis was performed for 192 patients in whom serial changes for both eGFR and TKV were obtained. eGFR slope, eGFR change, and TKV change values were as follows: - 2.7 (- 4.2 to - 1.5) (ml/min/1.73 m/year), - 5.0 (- 9.6 to - 2.3) (%/year), and 4.78 (0.86-8.22) (%/year), respectively. Lower high-density lipoprotein (HDL) cholesterol was an independent predictor of eGFR decline, using both eGFR slope and change (P = 0.04, P = 0.02, respectively), whereas lower hemoglobin and higher uric acid were significantly associated with greater eGFR change only (P = 0.02, P = 0.002, respectively). Younger age and higher fasting blood sugar were independent predictors of greater TKV change (P = 0.01, P = 0.02, respectively).

Conclusions: This real-world study in Japan identified risk factors for renal function decline in ADPKD patients. These included lower HDL cholesterol, lower hemoglobin and higher uric acid for eGFR decline, and youth and higher blood sugar levels for TKV growth.
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http://dx.doi.org/10.1007/s10157-021-02068-xDOI Listing
April 2021

Relationship between mortality and use of sodium bicarbonate at the time of dialysis initiation: a prospective observational study.

BMC Nephrol 2021 Apr 6;22(1):118. Epub 2021 Apr 6.

Division of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Patients with chronic kidney disease often experience metabolic acidosis. Whether oral sodium bicarbonate can reduce mortality in patients with metabolic acidosis has been debated for years. Hence, this study was conducted to evaluate the utility of sodium bicarbonate in patients who will undergo dialysis therapy. In this study, we investigated the effect of oral sodium bicarbonate therapy on mortality in patients with end-stage kidney disease (ESKD) initiated on dialysis therapy.

Methods: We conducted an observational study of patients when they started dialysis therapy. There were 17 centres participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis. Data were available on patients' sex, age, use of sodium bicarbonate, drug history, medical history, vital data, and laboratory data. We investigated whether patients on oral sodium bicarbonate for more than three months before dialysis initiation had a better prognosis than those without sodium bicarbonate therapy. The primary outcome was defined as all-cause mortality.

Results: The study included 1524 patients with chronic kidney disease who initiated dialysis between October 2011 and September 2013. Among them, 1030 were men and 492 women, with a mean age of 67.5 ± 13.1 years. Of these, 677 used sodium bicarbonate and 845 did not; 13.6% of the patients in the former group and 21.2% of those in the latter group died by March 2015 (p <  0.001). Even after adjusting for various factors, the use of sodium bicarbonate independently reduced mortality (p <  0.001).

Conclusions: The use of oral sodium bicarbonate at the time of dialysis initiation significantly reduced all-cause mortality in patients undergoing dialysis therapy.
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http://dx.doi.org/10.1186/s12882-021-02330-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025509PMC
April 2021

C1 inhibitor mitigates peritoneal injury in zymosan-induced peritonitis.

Am J Physiol Renal Physiol 2021 06 5;320(6):F1123-F1132. Epub 2021 Apr 5.

Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan.

Peritonitis, due to a fungal or bacterial infection, leads to injury of the peritoneal lining and thereby forms a hazard for the long-term success of peritoneal dialysis (PD) and remains a lethal complication in patients with PD. This study investigated whether C1 inhibitor (C1-INH) could protect against the progression of peritoneal injuries with five daily administrations of zymosan after mechanical scraping of the rat peritoneum to mimic fungal peritonitis. Severe peritoneal injuries were seen in this model, accompanied by fibrinogen/fibrin exudation and peritoneal deposition of complement activation products such as activated C3 and C5b-9. However, intraperitoneal injection of C1-INH decreased peritoneal depositions of activated C3 and C5b-9, ameliorated peritoneal thickening, reduced the influx of inflammatory cells, and prevented the production of peritoneal fibrous layers with both one and two doses of C1-INH each day. Our results suggest that C1-INH might be useful to protect against peritoneal injuries after causes of peritonitis such as fungal infection. This clinically available agent may thus help extend the duration of PD. Peritoneal injuries associated with peritonitis comprise an important issue to prevent long-term peritoneal dialysis (PD) therapy. Here, we showed that C1 inhibitor (C1-INH), as an anticomplement agent, protected against peritoneal injuries in a peritonitis animal model related to fungal infection. Therefore, C1-INH might be useful to protect against peritoneal injuries after peritonitis due to fungal infection. This clinically available agent may thus help extend the duration of PD.
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http://dx.doi.org/10.1152/ajprenal.00600.2020DOI Listing
June 2021

Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer.

JCI Insight 2021 May 10;6(9). Epub 2021 May 10.

Division of Cancer Immunology, Research Institute/Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo/Chiba, Japan.

Patients with colorectal cancers (CRCs) generally exhibit improved survival through intensive lymph node (LN) dissection. However, recent progress in cancer immunotherapy revisits the potential importance of regional LNs, where T cells are primed to attack tumor cells. To elucidate the role of regional LN, we investigated the immunological status of nonmetastatic regional LN lymphocytes (LNLs) in comparison with those of the tumor microenvironment (tumor-infiltrating lymphocytes; TILs) using flow cytometry and next-generation sequencing. LNLs comprised an intermediate level of the effector T cell population between peripheral blood lymphocytes (PBLs) and TILs. Significant overlap of the T cell receptor (TCR) repertoire was observed in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) CRCs with high tumor mutation burden (TMB), although limited TCRs were shared between nonmetastatic LNs and primary tumors in microsatellite stable/MMR proficient (MSS/pMMR) CRC patients with low TMB. In line with the overlap of the TCR repertoire, an excessive LN dissection did not provide a positive impact on long-term prognosis in our MSI-H/dMMR CRC cohort (n = 130). We propose that regional LNs play an important role in antitumor immunity, particularly in MSI-H/dMMR CRCs with high TMB, requiring care to be taken regarding excessive nonmetastatic LN dissection in MSI-H/dMMR CRC patients.
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http://dx.doi.org/10.1172/jci.insight.137365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262295PMC
May 2021

Refractory Hypotension Caused by Selenium Deficiency in a Patient on Peritoneal Dialysis.

Intern Med 2021 Aug 15;60(15):2461-2464. Epub 2021 Feb 15.

Department of Nephrology, Nagoya University Graduate School of Medicine, Japan.

Selenium is essential for human health; its deficiency leads to cardiac dysfunction. We herein report a 79-year-old man on peritoneal dialysis who presented with refractory hypotension caused by selenium deficiency. He was admitted to our hospital with bacterial pneumonia and hypotension and abnormal electrocardiogram (ECG) findings. Despite improvement of pneumonia, his hypotension continued, and intravenous noradrenalin could not be discontinued. His serum selenium level was extremely low, and he was started on intravenous selenium. His hypotension and ECG findings gradually improved, and noradrenalin was discontinued. Physicians should consider selenium deficiency when patients on peritoneal dialysis show refractory hypotension.
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http://dx.doi.org/10.2169/internalmedicine.6632-20DOI Listing
August 2021

Oral Antibiotics are Effective for Preventing Colonoscopy-associated Peritonitis as a Preemptive Therapy in Patients on Peritoneal Dialysis.

Intern Med 2021 1;60(3):353-356. Epub 2021 Feb 1.

Department of Nephrology and Rheumatology, Aichi Medical University, Japan.

Objective In patients on peritoneal dialysis (PD), it was reported that colonoscopy, but not upper gastrointestinal endoscopy, could cause peritonitis as a complication. A guideline of the International Society for Peritoneal Dialysis recommends preemptive intravenous antibiotics administration of ampicillin and aminoglycoside with or without metronidazole, to prevent colonoscopy-associated peritonitis. In this study, we retrospectively evaluated the effects of preemptive antibiotics therapy by oral administration instead of intravenous administration. Methods We investigated the incidence of colonoscopy-associated peritonitis in a single center. In 170 patients undergoing PD between January 2010 and December 2019, 50 colonoscopies were performed, including 49 with oral administration of amoxicillin and ciprofloxacin and/or metronidazole as preemptive therapy 1 hour before the colonoscopy procedure, and 1 without. Results We observed no incidence of colonoscopy-associated peritonitis. Conclusion Generally, oral administration of preemptive antibiotics is less painful and more convenient than intravenous administration, especially in outpatient procedures, such as a colonoscopy. Our results suggest that oral antibiotic administration might be effective for preventing colonoscopy-associated peritonitis in PD patients.
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http://dx.doi.org/10.2169/internalmedicine.5092-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925264PMC
April 2021

Clinical manifestations of focal segmental glomerulosclerosis in Japan from the Japan Renal Biopsy Registry: age stratification and comparison with minimal change disease.

Sci Rep 2021 Jan 28;11(1):2602. Epub 2021 Jan 28.

Department of Internal Medicine, Sendai Hospital of East Japan Railway Company, Sendai, Japan.

Focal segmental glomerulosclerosis (FSGS) is a serious condition leading to kidney failure. We aimed to investigate the clinical characteristics of FSGS and its differences compared with minimal change disease (MCD) using cross-sectional data from the Japan Renal Biopsy Registry. In Analysis 1, primary FSGS (n = 996) were stratified by age into three groups: pediatric (< 18 years), adult (18-64 years), and elderly (≥ 65 years), and clinical characteristics were compared. Clinical diagnosis of nephrotic syndrome (NS) was given to 73.5% (97/132) of the pediatric, 41.2% (256/622) of the adult, and 65.7% (159/242) of the elderly group. In Analysis 2, primary FSGS (n = 306) and MCD (n = 1303) whose clinical diagnosis was nephrotic syndrome (NS) and laboratory data were consistent with NS, were enrolled. Logistic regression analysis was conducted to elucidate the variables which can distinguish FSGS from MCD. On multivariable analysis, higher systolic blood pressure, higher serum albumin, lower eGFR, and presence of hematuria associated with FSGS. In Japanese nationwide registry, primary FSGS patients aged 18-64 years showed lower rate of NS than those in other ages. Among primary nephrotic cases, FSGS showed distinct clinical features from MCD.
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http://dx.doi.org/10.1038/s41598-020-80931-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844271PMC
January 2021

Cardiovascular disease history and β-blocker prescription patterns among Japanese and American patients with CKD: a cross-sectional study of the CRIC and CKD-JAC studies.

Hypertens Res 2021 Jun 22;44(6):700-710. Epub 2021 Jan 22.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, at the University of Pennsylvania, Philadelphia, PA, USA.

Cardiovascular disease (CVD) is a major complication in individuals with chronic kidney disease (CKD). In Japan, the incidence of CVD among persons with CKD is lower than that in the United States. Although various classes of antihypertensive agents are prescribed to prevent CVD, the proportion varies between the United States and Japan. Until now, few studies have compared clinical practices and CVD prevalence among patients with CKD in the United States vs. Japan. In this study, we performed a cross-sectional comparison of the prevalence of CVD and the prescription of β-blockers at study entry to the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study and the Chronic Renal Insufficiency Cohort (CRIC) Study. The mean patient age was 58.2 and 60.3 years, the mean estimated glomerular filtration rate (eGFR) was 42.8 and 28.9 (mL/min/1.73 m), and the median urinary albumin:creatinine ratio was 51.9 and 485.9 (mg/g) among 3939 participants in the CRIC Study and 2966 participants in the CKD-JAC Study, respectively. The prevalence of any CVD according to a self-report (CRIC Study) was 33%, while that according to a medical chart review (CKD-JAC Study) was 24%. These findings were consistent across eGFR levels. Prescriptions for β-blockers differed between the CRIC and CKD-JAC Studies (49% and 20%, respectively). The odds ratios for the association of any history of CVD and β-blocker prescription were 3.0 [2.6-3.5] in the CRIC Study and 2.0 [1.6-2.5] in the CKD-JAC Study (P < 0.001 for the interaction). In conclusion, the prevalence of CVD and treatment with β-blockers were higher in the CRIC Study across eGFR levels.
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http://dx.doi.org/10.1038/s41440-020-00608-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184630PMC
June 2021

The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis.

Sci Rep 2021 Jan 15;11(1):1525. Epub 2021 Jan 15.

Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Lupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification-including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels-and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.
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http://dx.doi.org/10.1038/s41598-020-78972-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810677PMC
January 2021

Nephrotic syndrome with focal segmental glomerular lesions unclassified by Columbia classification; Pathology and clinical implication.

PLoS One 2021 5;16(1):e0244677. Epub 2021 Jan 5.

Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: The Columbia classification is widely used for diagnosis of focal segmental glomerulosclerosis (FSGS). In practice, we occasionally encounter segmental glomerular lesions unclassified as Columbia classification. We analyzed the clinical implication of unclassified segmental lesions comparing with Columbia-classified FSGS.

Methods: A retrospective cohort study from 13 local hospitals in Japan. From 172 biopsy cases diagnosed with FSGS or minimal change disease (MCD)/FSGS spectrum with unclassified segmental lesions, adult patients with nephrotic syndrome who received immunosuppressive therapies were included. The cases are classified by pathology, i.e., typical FSGS lesions sufficiently classified into subgroups of Columbia classification: collapsing (COL), tip (TIP), cellular (CEL), perihilar (PH), and not otherwise specified (NOS), and unclassified by the Columbia classification into three subgroups: "endothelial damage,"; "simple attachment,"; and "minor cellular lesion,". The response to immunosuppressive treatment and 30% decline of eGFR were compared.

Results: Among 48 eligible cases, all were Japanese, 34 were typical FSGS; 13 TIP, 15 CEL, 6 NOS, and no COL or PH cases. Fourteen were unclassified cases: endothelial damage (n = 6), simple attachment (n = 5), and minor cellular lesion (n = 3). The median age of overall patients was 60 years old and the median of eGFR and urinary protein creatinine ratio was 51.5 mL/min/1.73m2 and 7.35, respectively. They received similar therapeutic regimen. Kaplan-Meier analysis revealed no significant difference in treatment response between typical FSGS and unclassified cases. Evaluating among the subgroups, endothelial damage, simple attachment and minor cellular lesion showed similar treatment response to TIP or CEL. No significant difference was also observed in the 30% decline of eGFR.

Conclusions: Japanese adult patients with nephrotic syndrome showing unclassified segmental lesions as Columbia classification may be equivalent clinical impact as Columbia classification of FSGS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244677PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785116PMC
May 2021

Validity of "One-size-fits-all" Approaches for the National Health Screening and Education Program: A Large-scale Cohort Study of Corporate Insurance Beneficiaries.

Intern Med 2021 Jun 29;60(11):1681-1689. Epub 2020 Dec 29.

Department of Nephrology, Nagoya University Graduate School of Medicine, Japan.

Objective Metabolic syndrome represents a unified condition of atherosclerotic diseases caused by abdominal obesity. The aims of this study were to examine the applicability of the prevalent fixed cut-off values of the abdominal circumference (AC) and body mass index (BMI) to age and gender groups and to identify suitable lifestyle modification factors. Methods We defined an outcome as having ≥ 2 risk components that are necessary to diagnose metabolic syndrome and examined the cross-sectional association of the AC and BMI with the outcome. We also assessed the effects of time-updated lifestyle information on metabolic traits using longitudinal data. Patients We enrolled 22,953 beneficiaries of a corporate health insurance scheme who underwent annual health examinations between January 2004 and December 2014. Results The AC [per 5-cm increase, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.12-1.24] and BMI (OR 1.10, 95% CI 1.07-1.13) were significantly associated with the outcome, adjusted for age, gender, current smoking status, drinking habits, and other lifestyle information. The association between the outcome and AC was modified by gender (p for interaction = 0.033), and the association between the outcome and BMI was modified by age group (p for interaction = 0.049). In the longitudinal analysis, current smoking, drinking habits, and unhealthy eating habits were associated with an increased AC and BMI, whereas regular physical activity was associated with a decreased AC and BMI. Conclusion We showed that the association between the AC or BMI and metabolic syndrome was modified by gender or age group. Further studies will be needed to customize the national health screening and education programs.
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http://dx.doi.org/10.2169/internalmedicine.5515-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222130PMC
June 2021

Peripheral artery disease at the time of dialysis initiation and mortality: a prospective observational multicenter study.

BMJ Open 2020 12 31;10(12):e042315. Epub 2020 Dec 31.

Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: Patients with peripheral artery disease (PAD) are reported to have a poorer prognosis than those without PAD. PAD is sometimes found at dialysis initiation, but its influence on the prognosis in these patients has not been investigated. We aimed to compare the mortality rate between patients with PAD at the time of dialysis initiation and those without PAD.

Design: We undertook an observational prospective multicenter study of patients starting dialysis treatment. Data were collected on patients' sex, age, presence of PAD, medication, medical history and clinical and laboratory data.

Setting: Seventeen centers participated in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis.

Participants: A total of 1524 patients with chronic kidney disease started dialysis from October 2011 to September 2013. The patients were followed-up until March 2015. During this time, there were two patients who lost the follow-up.

Primary And Secondary Outcome Measures: The primary outcome was defined as all-cause mortality. The secondary outcomes were defined as each cause of mortality.

Results: This study included 1030 men and 492 women with a mean age of 67.50±13.10 years. Of these, 71 had PAD and 1451 did not have PAD. After a median follow-up of 814.5 days, 33.80% of the former group and 17.00% of the latter group had died in March 2015 (p=0.001). After adjusting for confounding factors, PAD at dialysis initiation remained an independent risk factor for mortality (p<0.01).

Conclusions: Patients with PAD at the time of dialysis initiation had a poorer prognosis than patients without PAD. Therefore, the presence of PAD in patients starting dialysis should be considered for their monitoring and follow-up.
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http://dx.doi.org/10.1136/bmjopen-2020-042315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780557PMC
December 2020

A Prospective, Randomized Clinical Trial of Etelcalcetide in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism (the DUET Trial).

Kidney Int Rep 2020 Dec 18;5(12):2168-2177. Epub 2020 Sep 18.

Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan.

Introduction: The clinical trial on the Development of a treatment strategy for chronic kidney disease‒mineral and bone disorder by a mUltilateral mechanism of ETelcalcetide hydrochloride, or the DUET trial, was designed to determine the efficacy of etelcalcetide, an intravenous calcimimetic, for control of secondary hyperparathyroidism (SHPT).

Methods: Eligible SHPT maintenance hemodialysis patients (n = 124) were randomized (1:1:1) for inclusion in the DUET trial, a 12-week, multicenter, open-label, parallel-group study (jRCTs041180108), and assigned to either an etelcalcetide + active vitamin D group (group E+D), an etelcalcetide + oral calcium preparation group (group E+Ca), or a control group (group C). The primary endpoint was number of patients with a 50% reduction from baseline of intact parathyroid hormone (iPTH) levels, and iPTH levels ≤ 240 pg/mL at 12 weeks after start of the trial.

Results: The proportion of patients reaching the primary endpoint (95% confidence interval [CI]) was 90.0% (76.3%-97.2%) in group E+D, 56.8% (39.5%-72.9%) in group E+Ca, and 19.5% (8.8%-34.9%) in group C. Etelcalcetide treatment led to a significant increase in the number of patients achieving the endpoint (odds ratio, 13.4; 95% CI, 5.10-35.3) on logistic regression analysis, with iPTH, corrected serum calcium, and phosphate at baseline as covariates. Significantly more patients achieved the endpoint in group E+D compared with group E+Ca (odds ratio, 6.35; 95% CI, 1.79-22.48). There were fewer hypocalcemic visits in group E+D compared with group E+Ca ( = 0.018), yet the former group was prone to hyperphosphatemia.

Conclusion: Etelcalcetide showed good control of iPTH for maintenance hemodialysis patients with SHPT. Active vitamin D was useful in correcting hypocalcemia, but the oral calcium preparation was superior for suppression of hyperphosphatemia.
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http://dx.doi.org/10.1016/j.ekir.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710846PMC
December 2020

Prognostic Impact of Parameters of Metabolic Acidosis in Critically Ill Children with Acute Kidney Injury: A Retrospective Observational Analysis Using the PIC Database.

Diagnostics (Basel) 2020 Nov 11;10(11). Epub 2020 Nov 11.

Division of Nephrology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.

Acute kidney injury (AKI) is a major complication of sepsis that induces acid-base imbalances. While creatinine levels are the only indicator for assessing the prognosis of AKI, prognostic importance of metabolic acidosis is unknown. We conducted a retrospective observational study by analyzing a large China-based pediatric critical care database from 2010 to 2018. Participants were critically ill children with AKI admitted to intensive care units (ICUs). The study included 1505 children admitted to ICUs with AKI, including 827 males and 678 females. The median age at ICU admission was 22 months (interquartile range 7-65). After a median follow-up of 10.87 days, 4.3% (65 patients) died. After adjusting for confounding factors, hyperlactatemia, low pH, and low bicarbonate levels were independently associated with 28-day mortality (respective odds ratio: 3.06, 2.77, 2.09; values: <0.01, <0.01, <0.01). The infection had no interaction with the three parameters. The AKI stage negatively interacted with bicarbonate and pH but not lactate. The current study shows that among children with AKI, hyperlactatemia, low pH, and hypobicarbonatemia are associated with 28-day mortality.
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http://dx.doi.org/10.3390/diagnostics10110937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696045PMC
November 2020

Long-term changes in renal function after treatment initiation and the importance of early diagnosis in maintaining renal function among IgG4-related tubulointerstitial nephritis patients in Japan.

Arthritis Res Ther 2020 11 5;22(1):261. Epub 2020 Nov 5.

Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.

Background: The present study aimed to investigate associations between long-term renal function, whether IgG4-related tubulointerstitial nephritis (TIN) was diagnosed by renal biopsy at initial examination, chronic kidney disease (CKD) stage, and histological stage in patients with IgG4-related TIN.

Methods: This study used a retrospective cohort design including almost all patients who underwent renal biopsy at Fujita Health University Hospital and Nagoya University or its affiliated hospitals in Aichi between April 2003 and March 2015 (n = 6977 renal biopsies). The primary outcome was longitudinal changes in eGFR. Main exposures were whether IgG4-related TIN was diagnosed by renal biopsy at the initial examination, CKD stage, and its histological stage. Linear mixed models were performed to examine associations.

Results: Of the 6977 samples, there were 24 patients (with 201 records due to repeated measures) with IgG4-related TIN (20 men, mean age, 68.7 ± 9.7 years). They were followed up 6.6 ± 2.8 years after the renal biopsy and underwent glucocorticoid treatment. We found significant increase in eGFR from the baseline to 2 and 6 months after treatment initiation, which was maintained until 60 months. Patients initially diagnosed with IgG4-related TIN had higher eGFR from the baseline (at the start of treatment) to 60 months than those who were not. Compared with patients with CKD stage 3, patients with CKD stages 4 and 5 had lower eGFR at the baseline and other time points. Patients with histological stage B had comparatively lower eGFR at each point than stage A patients. Those mean differences of eGFR were stable from the baseline to 60 months.

Conclusions: After the treatment initiation, renal function rapidly improved and maintained for a long period, even with advanced CKD stage. We showed importance of early diagnosis of IgG4-related TIN in maintaining eGFR.
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http://dx.doi.org/10.1186/s13075-020-02320-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643351PMC
November 2020

Vascular endothelial growth factor (VEGF)-A and VEGF-Ab are associated with time to remission of granulomatosis with polyangiitis in a nationwide Japanese prospective cohort study.

Ann Clin Biochem 2021 03 22;58(2):86-94. Epub 2020 Nov 22.

Nagoya University, Nagoya, Japan.

Background: Effective prognostic markers are needed for antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the clinical associations of serum vascular endothelial growth factor-A (sVEGF-A) and sVEGF-Ab (an antiangiogenic isoform of VEGF-A) concentrations with time to remission of AAV in a nationwide Japanese prospective follow-up cohort.

Methods: We collected samples from patients with AAV who were enrolled in the nationwide Japanese cohort study (RemIT-JAV-RPGN). We measured sVEGF-A and sVEGF-Ab concentrations using enzyme-linked immunosorbent assays in 57 serum samples collected 6 months before and after initiation of AAV treatment. Patients were classified based on AAV disease subtypes: microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA).

Results: Results revealed significant reductions in sVEGF-A and sVEGF-Ab concentrations in patients with microscopic polyangiitis and EGPA, respectively. However, despite the comparable concentrations of sVEGF-A and sVEGF-Ab during the 6 months of treatment in granulomatosis with polyangiitis patients, correlation analysis revealed that the differences in log-transformed concentrations of sVEGF-A and sVEGF-Ab were inversely correlated with time to remission in granulomatosis with polyangiitis patients.

Conclusion: These results suggest that sVEGF-A and -Ab can serve as potential markers of time to remission in patients with granulomatosis with polyangiitis.
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http://dx.doi.org/10.1177/0004563220968371DOI Listing
March 2021

Prevalences of hyperuricemia and electrolyte abnormalities in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

PLoS One 2020 15;15(10):e0240402. Epub 2020 Oct 15.

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD.

Methods: In total, 35,508 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.

Results: Logistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90-2.37]), G4 (4.57 [3.92-5.32]), and G5 (2.25 [1.80-2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively.

Conclusions: We determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240402PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561156PMC
December 2020

High urinary glucose is associated with improved renal prognosis in patients with diabetes mellitus.

J Diabetes Investig 2021 Jun 16;12(6):998-1006. Epub 2020 Nov 16.

Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Aims/introduction: The relationship between renal function and urinary glucose is poorly understood in diabetes patients who are not using sodium-glucose cotransporter 2 inhibitors. This study aimed to investigate the association of urinary glucose excretion with renal function prognosis in such patients.

Materials And Methods: This retrospective cohort study included 1,172 patients with type 1 or 2 diabetes mellitus. Patients were recruited and data were collected between 1 January 2007 and 31 December 2011; follow-up data were collected until 30 June 2015. The primary outcome was set as a 30% decline in estimated glomerular filtration rate relative to baseline. The relationship between this outcome and urinary glucose was investigated using Cox proportional hazards model. For analysis, patients were categorized into two groups: urinary glucose <5 g/day or ≥5 g/day. Interaction terms were analyzed.

Results: Multivariate analysis showed that the prognosis of renal function was significantly better in patients with high urinary glucose (≥5 g/day; adjusted hazard ratio 0.58, 95% confidence interval 0.35-0.96; P = 0.034). Significant interactions were observed between high urinary glucose and male sex (hazard ratio 0.33, 95% confidence interval 0.14-0.74; P = 0.007), and between high urinary glucose and longer duration of diabetes (≥10 years; hazard ratio 0.25, 95% confidence interval 0.11-0.58; P = 0.001).

Conclusions: The present study suggests that high urinary glucose is associated with prognosis in diabetes patients not taking sodium-glucose cotransporter 2 inhibitors. Measurement of 24-h urinary glucose excretion might have clinical utility for predicting renal prognosis.
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http://dx.doi.org/10.1111/jdi.13428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169355PMC
June 2021

Acquired Fanconi Syndrome in a Patient with Nontyphoidal Salmonella Bacteremia.

Intern Med 2021 Mar 30;60(5):761-764. Epub 2020 Sep 30.

Department of Nephrology, Nagoya University Graduate School of Medicine, Japan.

Nontyphoidal Salmonella is a common cause of bacterial gastroenteritis, occasionally causing bacteremia. We herein report the case of an 80-year-old man who presented with bacteremia and pre-renal acute kidney injury (AKI) secondary to diarrhea caused by nontyphoidal Salmonella. Despite AKI improvement on fluid administration, some serological abnormalities, such as hypokalemia, hypophosphatemia, and hypouricemia, and abnormal urinary findings emerged, including renal glycosuria and aminoaciduria. Fractional excretion of phosphate and uric acid was increased, suggesting that the serological and urinary abnormalities may have arisen from Fanconi syndrome. Physicians should consider acquired Fanconi syndrome when patients with nontyphoidal Salmonella bacteremia present with electrolyte disorders.
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http://dx.doi.org/10.2169/internalmedicine.5932-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990623PMC
March 2021

Glucocorticoid treatment is associated with ICU-acquired hypernatremia: a nested case-control study.

Clin Exp Nephrol 2021 Feb 22;25(2):131-139. Epub 2020 Sep 22.

Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: Hypernatremia is a major electrolyte disorder associated with death among critically ill patients. Glucocorticoid therapy may cause hypernatremia in refractory septic shock patients, but the association between glucocorticoid and intensive care unit (ICU)-acquired hypernatremia (IAH) remains unclear. The aim of this study was to clarify whether glucocorticoid administration was associated with IAH.

Methods: This was a nested case-control study using data from an established cohort including 121 IAH cases identified from 1756 patients who were admitted to ICU in a tertiary care facility in Japan. We included patients who were admitted with a normal range of serum sodium concentrations (130-149 mEq/L) from January 1, 2013 to December 31, 2015 and remained in ICU for ≥ 2 days. Hypernatremia was defined as serum sodium concentration ≥ 150 mEq/L. Each case was matched to one control.

Results: Multivariable conditional logistic regression revealed high-dose glucocorticoid {odds ratio (OR), 4.15 [95% confidence interval (CI) 1.29-13.4]}, acute kidney injury (AKI) [OR, 2.72 (95% CI 1.31-5.62)], and osmotic diuretics [OR, 3.44 (95% CI 1.41-8.39)] to be significantly associated with IAH. The contents and amounts of fluid infusion were not significantly associated with IAH. There were also significant duration-response effects between duration of glucocorticoid use and IAH; however, pulse glucocorticoid administration was not associated with IAH.

Conclusion: In this nested case-control study, we demonstrated a significant association between IAH and high-dose glucocorticoid with significant duration-response effects. Serum sodium concentrations should be monitored carefully in critically ill patients administered prolonged high-dose glucocorticoid.
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http://dx.doi.org/10.1007/s10157-020-01967-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506169PMC
February 2021

Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan.

Clin Exp Nephrol 2021 Feb 19;25(2):110-119. Epub 2020 Sep 19.

Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibancho Asahimachidori Chuo-ku, Niigata, 951-8510, Japan.

Background: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN.

Methods: Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed.

Results: The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15-900 μg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein-creatinine ratio were independently associated with better initial response to DA (P =  < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively).

Conclusions: Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.
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http://dx.doi.org/10.1007/s10157-020-01969-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880978PMC
February 2021

Efficacy of favipiravir for an end stage renal disease patient on maintenance hemodialysis infected with novel coronavirus disease 2019.

CEN Case Rep 2021 02 17;10(1):126-131. Epub 2020 Sep 17.

Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: Novel coronavirus disease 2019 (COVID-19) refers to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, and has spread to pandemic levels since its inception in December 2019. While several risk factors for severe presentation have been identified, the clinical course for end-stage renal disease (ESRD) patients on maintenance hemodialysis with COVID-19 has been unclear. Previous studies have revealed that some antiviral agents may be effective against COVID-19 in the general population, but the pharmacokinetics and pharmacodynamics of these agents in ESRD patients remain under investigation. Favipiravir, an antiviral agent developed for treatment of influenza, is one candidate treatment for COVID-19, but suitable dosages for patients with renal insufficiency are unknown. Here we provide a first report on the efficacy of favipiravir in a patient with ESRD undergoing hemodialysis.

Case Presentation: The case involved a 52-year-old woman with COVID-19 who had been undergoing maintenance hemodialysis three times a week for 3 years due to diabetic nephropathy. She had initially been treated with lopinavir/ritonavir and ciclesonide for 5 days, but developed severe pneumonia requiring invasive positive-pressure ventilation. Those antiviral agents were subsequently switched to favipiravir. She recovered gradually, and after 2 weeks was extubated once the viral load of SARS-CoV-2 fell below the limit of detection. Although concentrations of several biliary enzymes were elevated, no major adverse events were observed.

Conclusion: Favipiravir may be an effective option for the treatment of COVID-19-infected patients with ESRD.
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http://dx.doi.org/10.1007/s13730-020-00534-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494976PMC
February 2021
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