Search

Abstract Heart failure (HF) is a frequent complication and the main cause of death in patients on dialysis. HF with preserved ejection fraction (HFpEF) is a complicated syndrome that manifests as diastolic dysfunction and increased left ventricular filling pressure. Few studies have investigated HFpEF in dialysis patients, so the diagnosis and treatment of HFpEF remains challenging. The recently published the Japanese Circulation Society (JCS)/the Japanese Heart Failure Society (JHFS) 2021 guidelines have reported a new diagnostic procedure for HF. In dialysis patients, HF is typically observed as left ventricular diastolic dysfunction in association with HFpEF. Recent reports have shown that risk factors for HF in dialysis patients include not only traditional risk factors, such as age, smoking, obesity, hypertension, dyslipidemia, and diabetes, but also nontraditional risk factors such as fluid overload, renal anemia, disorders of calcium and phosphate metabolism, uremic toxins, and malnutrition. In the management of dialysis patients, volume control is important for controlling intradialytic hypotension, which is associated with higher mortality. Also, adequate pharmacological treatment of HFpEF is difficult in these patients, so a robust protocol developed for non-dialysis patients with HFpEF may be useful for treating patients on dialysis. This review explores the characteristics of hemodialysis patients with HFpEF and diagnostic and treatment procedures for these patients.

Abstract Patients on peritoneal dialysis (PD) have a high prevalence of cardiovascular complications and are at increased risk of cardiovascular mortality. Dialysis increases the likelihood of developing various cardiovascular complications, including ischemic heart disease, cardiac valvular disease, hypertensive cardiomyopathy, and arrhythmias. However, noncardiac circulatory failure can also occur in the absence of obvious cardiac disease in PD patients as a result of excessive fluid volume. Other important causes of nontraditional circulatory failure in these patients include mineral imbalance and severe anemia. In this review, I focus on nontraditional risk factors for cardiovascular disease in PD patients, including ultrafiltration failure, chronic kidney disease–mineral bone disorders, anemia, inflammation, and sarcopenia.

We aimed to develop a novel method for measuring the complement-binding ability of anti-blood type antibodies (ab-Abs), the flow cytometry method for the complement C1q test (FCM-C1q) for detecting antibody-mediated rejection (AMR) caused by ab-Abs in ABO-incompatible kidney transplantation (ABOI-KTx). FCM-C1q distribution was surveyed in 44 healthy participants and 43 dialysis patients (Cohort A). The relationship between AMR and FCM-C1q levels was examined along with ab-Ab titers by the flow cytometry method for the IgG test (FCM-IgG) in 62 ABOI-KTx patients (Cohort B). FCM-IgG and C1q levels were significantly higher in type O participants than in A/B participants in Cohort A. There were minimal differences in the distribution of FCM-IgG and C1q between dialysis and healthy participants. Sixteen cases were suspected of acute rejections (ARs) in Cohort B, of whom nine had AR clinically. One patient with severe AMR was highly suspected of hyperacute rejection along with another patient with severe AMR. Their postoperative FCM-C1q and FCM-IgG levels were elevated. Another two patients showed high FCM-IgG and C1q levels before KTx, and these levels remained low after KTx with no or mild rejection. In conclusion, our results suggest that a high positivity rate for FCM-C1q may predict moderate to severe AMR caused by ab-Abs and poor prognosis in ABOI-KTx.

The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy.

Abstract Background With the constant need for technique improvement for ensuring correct diagnoses and precise treatment, imaging examinations that use contrast media have become unavoidable and indispensable. However, the long-term effects of contrast media on renal function remain unclear in populations with advanced renal failure. This study aimed to examine the relationship between contrast media exposure and long-term trends in renal function in patients with renal failure. Methods This retrospective cohort study included patients with a definitive diagnosis of chronic kidney disease who visited medical institutions in Japan between April 2012 and December 2020. The cohort was divided into contrast agent therapy and non-contrast agent therapy groups. The assessment indices were the number of contrast exposures and renal function decline. Renal function decline was calculated based on observed chronic kidney disease stage trends and glomerular filtration rate correspondence tables sourced from various guidelines. A stratified analysis focusing on changes in renal function while accounting for the acceleration of chronic kidney disease progression was also performed. Results After adjusting for patient background with propensity score matching, 333 patients each were included in both groups. The observation period was 5.3 ± 2.1 and 4.9 ± 2.2 years per case in the contrast-enhanced and non-contrast-enhanced groups, respectively. The baseline estimated glomerular filtration rate at the beginning of the observation period was 55.2 ± 17.8 mL/min/1.73 m2 in the contrast-enhanced groups (P = 0.65). Although only slightly different in both groups, the glomerular filtration rate change was 1.1 ± 3.3 mL/min/1.73 m2/year in the contrast agent therapy group and tended to be higher with contrast media exposure. Stratified analysis showed that the annual glomerular filtration rate changes in patients with more contrast media exposures and altered renal function were 7.9 ± 7.1 mL/min/1.73 m2/year and 4.7 ± 3.6 mL/min/1.73 m2/year in the contrast agent therapy and non-contrast agent therapy groups, respectively (1.69 times, P

Chronic kidney disease—mineral and bone disorder (CKD-MBD) is a systemic disorder that increases the risk of morbidity and mortality in dialysis patients. CKD-MBD is highly prevalent in dialysis patients, and appropriate treatment is important for improving their outcomes. Inorganic phosphate, fibroblast growth factor 23, parathyroid hormone, and calciprotein particles are markers for critical components and effectors of CKD-MBD, and higher circulating levels of these markers are linked to cardiovascular diseases. In this short review, we focus on the pathogenesis and management of CKD-MBD in CKD patients, especially those on dialysis therapy, and discuss the prospects for improving the management in CKD patients, including those on dialysis.

Abstract Frailty has become an emerging public health problem in the aging society and is regarded as a state of vulnerability to developing increased dependency and/or mortality when exposed to a stressor. As the proportion of elderly dialysis patients is increasing worldwide, frailty has recently influenced on the clinical outcomes among those patients also caused great attention. The prevalence of frailty among dialysis patients has ranged from 3.0- to 10-fold higher than in community-dwelling elderly. Since frailty has been found to be associated with higher mortality, independent of clinical characteristics and comorbidity, interventions to improve frailty have the potential to contribute to better quality of life and lower mortality among dialysis patients. Moreover, clinical research should be focused on the possibility that early rehabilitation of dialysis patients might improve poor outcomes. Current clinical question should aim to take an appropriate strategy to address frailty, including identifying the optimal timing for intervention.

Abstract Background The incidence of cardiovascular (CV) events is high in hemodialysis (HD) patients and is associated with hyporesponsiveness to erythropoiesis-stimulating agents (ESAs). However, there are no recommended target hemoglobin ranges for ESA-hyporesponsive patients. Methods We randomly assigned 304 ESA-treated HD patients with ESA hyporesponsiveness to a proactive treatment group (target hemoglobin level 11 g/dL) or maintenance treatment group (target hemoglobin level 9–10 g/dL), both of which received epoetin beta pegol. The primary outcome was time to the first CV event. CV events included cardiac death, heart failure, and acute coronary syndrome requiring hospitalization. The patients were followed for 24 months. Results The proactive and maintenance treatment groups had mean baseline hemoglobin levels of 9.34 and 9.32 g/dL, respectively. Mean hemoglobin levels during the observation period were 10.58 and 10.26 g/dL (P 10.5 g/dL were 11.5 and 8.6 months (P 10.5 g/dL was associated with a lower risk of CV events (HR, 0.92/month; 95% CI, 0.87–0.98). Conclusions Targeting hemoglobin levels of 11 g/dL with epoetin beta pegol reduces CV risk in Japanese HD patients with ESA hyporesponsiveness. Trial registration: University Hospital Medical Information Network (UMIN) database (UMIN000010138), registered on March 1, 2013.

Abstract A practical research method integrating data-driven machine learning with conventional model-driven statistics is sought after in medicine. Although glomerular hypertrophy (or a large renal corpuscle) on renal biopsy has pathophysiological implications, it is often misdiagnosed as adaptive/compensatory hypertrophy. Using a generative machine learning method, we aimed to explore the factors associated with a maximal glomerular diameter of ≥ 242.3 μm. Using the frequency-of-usage variable ranking in generative models, we defined the machine learning scores with symbolic regression via genetic programming (SR via GP). We compared important variables selected by SR with those selected by a point-biserial correlation coefficient using multivariable logistic and linear regressions to validate discriminatory ability, goodness-of-fit, and collinearity. Body mass index, complement component C3, serum total protein, arteriolosclerosis, C-reactive protein, and the Oxford E1 score were ranked among the top 10 variables with high machine learning scores using SR via GP, while the estimated glomerular filtration rate was ranked 46 among the 60 variables. In multivariable analyses, the R 2 value was higher (0.61 vs. 0.45), and the corrected Akaike Information Criterion value was lower (402.7 vs. 417.2) with variables selected with SR than those selected with point-biserial r. There were two variables with variance inflation factors higher than 5 in those using point-biserial r and none in SR. Data-driven machine learning models may be useful in identifying significant and insignificant correlated factors. Our method may be generalized to other medical research due to the procedural simplicity of using top-ranked variables selected by machine learning.

Recently, the usefulness of serum uromodulin (sUmod) as a novel renal biomarker has been attracting attention. Clinical evidence regarding sUmod measurements has been accumulated by analyzing cross-sectional data. However, little is known about the longitudinal data on sUmod. Therefore, we decided to investigate the variability of sUmod in patients with acute kidney injury due to different causes. High concentrations of sUmod have been observed in patients with acute tubular injury (ATI) and/or acute interstitial nephritis (AIN). sUmod could be used as an auxiliary diagnostic tool for ATI and AIN.

Abstract Presently, only personal or family history of intracranial aneurysm/subarachnoid hemorrhage (IA/SAH) has been established as a risk factor for IA in autosomal dominant polycystic kidney disease (ADPKD). This study aimed to verify the association between kidney function/volume and IAs in patients with ADPKD. This study included 519 patients with ADPKD. At baseline IA screening, the median age and estimated glomerular filtration rate were 44 years and 54.5 mL/min/1.73 m2, respectively. Family IA/SAH history was confirmed in 18.1% of the patients, and 54.3% of the patients had hypertension. The IA point prevalence was 12.5%. During clinical follow up of 3104 patient-years, de novo IA was detected in 29 patients (0.93% patient-years). The IA period prevalence was 18.1% (median age, 60 years). Multivariable logistic regression demonstrated that total kidney volume (TKV) ≥ 1000 mL (odds ratio [OR] = 2.81), height-adjusted TKV ≥ 500 mL (OR = 2.81), Mayo imaging classification Class 1D–1E (OR = 2.52), and chronic kidney disease stages 3–5 (OR = 2.31) were significantly associated with IA formation. IAs in patients with ADPKD may be associated not only with general risk factors for IAs but also with declining kidney function and increased KV. Kidney disease progression may contribute to effective IA screening and treatment planning in patients with ADPKD.

Abstract Background We experienced a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from November 2020 to February 2021, during the third wave of the pandemic in Japan. Methods We retrospectively assessed the characteristics and data of 20 inpatients undergoing hemodialysis who were hospitalized for treatment of diseases other than COVID-19 during the COVID-19 nosocomial outbreak (“inpatient,” IP), and of 10 outpatients undergoing hemodialysis who were hospitalized for the care of COVID-19 under outpatient visits (“outpatient,” OP). Results Eleven patients in the IP group (55%) and one in the OP group (10%) died. Kaplan–Meier analysis showed that the IP group died more rapidly than the OP group (p = 0.02). Multivariate analysis among all hemodialysis patients showed that the IP group was not at risk of mortality independently; however, the activity of daily life (ADL) dependency was found to be an independent factor in increasing the risk of mortality (hazard ratio: 7.618). Conclusion Our findings show that the nosocomial infected group has a worse prognosis, although it is not an independent predictor for the risk of mortality. ADL dependency could predict the risk of mortality in all hemodialysis patients with COVID-19 during the third wave pandemic in Japan.

The success of sodium-glucose cotransporter 2 inhibitors and bariatric surgery in patients with chronic kidney disease has highlighted the importance of glomerular hyperfiltration and hypertrophy in the progression of kidney disease. Sustained glomerular hyperfiltration and hypertrophy can lead to glomerular injury and progressive kidney damage. This article explores the relationship between obesity and chronic kidney disease, focusing on the roles of glomerular hyperfiltration and hypertrophy as hallmarks of obesity-related kidney disease. The pathological mechanisms underlying this association include adipose tissue inflammation, dyslipidemia, insulin resistance, chronic systemic inflammation, oxidative stress, and overactivation of the sympathetic nervous system, as well as the renin-angiotensin aldosterone system. This article explains how glomerular hyperfiltration results from increased renal blood flow and intraglomerular hypertension, inducing mechanical stress on the filtration barrier and post-filtration structures. Injured glomeruli increase in size before sclerosing and collapsing. Therefore, using extreme values, such as the maximal glomerular diameter, could improve the understanding of the data distribution and allow for better kidney failure predictions. This review provides important insights into the mechanisms underlying glomerular hyperfiltration and hypertrophy and highlights the need for further research using glomerular size, including maximum glomerular profile, calculated using needle biopsy specimens.

Abstract Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Abstract Background Genus Desulfovibrio species is a sulphate-reducing anaerobic gram-negative rod that resides in the human oral cavity and intestinal tract. It was reported as the causative pathogen of bacteraemia and abdominal infections, but not renal cyst infection, and Desulfovibrio fairfieldensis has higher pathogenicity than other Desulfovibrio species. Case presentation A 63-year-old man was on haemodialysis for end-stage renal failure due to autosomal dominant polycystic kidney disease. On admission, he had a persistent high-grade fever, right lumbar back pain, and elevated C-reactive protein levels. His blood and urine cultures were negative. He received ciprofloxacin and meropenem; however, there was no clinical improvement. Contrast-enhanced computed tomography and plain magnetic resonance imaging revealed a haemorrhagic cyst at the upper pole of the right kidney. The lesion was drained. Although the drainage fluid culture was negative, D. fairfieldensis was detected in a renal cyst using a polymerase chain reaction. After the renal cyst drainage, he was treated with oral metronidazole and improved without any relapse. Conclusions To the best of our knowledge, this is the first reported case of a renal cyst infection with Desulfovibrio species. D. fairfieldensis is difficult to detect, and polymerase chain reaction tests can detect this bacterium and ensure better management for a successful recovery.

Introduction: Valid prediction models or predictors of disease progression in children and young patients with autosomal dominant polycystic kidney disease (ADPKD) are lacking. Although total kidney volume (TKV) and Mayo imaging classification are generally used to predict disease progression in patients with ADPKD, it remains unclear whether germline mutation types are associated with these factors. We therefore investigated the association between mutation type and TKV and Mayo imaging classification among patients with ADPKD. Methods: A total of 129 patients with ADPKD who underwent genetic analyses were enrolled in the study. The associations between the severity of PKD (TKV ≥ 1000 ml and Mayo classes 1C–1E) and the PKD1 mutation types (nonsense mutation, frameshift or splicing mutation, and substitution) were evaluated. Results: Among the mutation types, only PKD1 splicing/frameshift mutation had significant associations with TKV ≥ 1000 ml in sex-adjusted and multivariable logistic analyses. Similarly, only the PKD1 splicing/frameshift mutation was significantly associated with Mayo 1C–1E in sex-adjusted and multivariable logistic analyses. PKD1 nonsense mutation, PKD1 substitution, or PKD1 mutation position had no significant association with TKV ≥ 1000 ml or Mayo 1C–1E. Conclusion: Kidney cyst severity differs according to the mutation types in PKD1. Patients with PKD1 splicing mutations or PKD1 frameshift mutations are associated with TKV ≥ 1000 ml or Mayo 1C–1E. Detailed assessment of mutation types may be useful for predicting renal prognosis in patients with ADPKD and may especially contribute to the care of a high-risk group of children with ADPKD.

Abstract Attribute-based medicine is essential for patient-centered medicine. To date, the groups of patients with chronic kidney disease (CKD) requiring urate-lowering therapy are clinically unknown. Herein, we evaluated the efficacy of febuxostat using a cross-classification, attribute-based research approach. We performed post hoc analysis of multicenter, randomized, double-blind, placebo-controlled trial data for 395 patients with stage 3 CKD and asymptomatic hyperuricemia. Participants were divided into febuxostat or placebo groups and subcohorts stratified and cross-classified by proteinuria and serum creatinine concentrations. In patients stratified based on proteinuria, the mean eGFR slopes were significantly higher in the febuxostat group than in the placebo group (P = 0.007) in the subcohort without proteinuria. The interaction between febuxostat treatment and presence of proteinuria in terms of eGFR slope was significant (P for interaction = 0.019). When cross-classified by the presence of proteinuria and serum creatinine level, the mean eGFR slopes significantly differed between the febuxostat and placebo groups (P = 0.040) in cross-classified subcohorts without proteinuria and with serum creatinine level ≥ median, but not in the cross-classified subcohorts with proteinuria and serum creatinine level

Visceral adipose tissue plays a central role in obesity and metabolic syndrome and is an independent risk factor for both cardiovascular and metabolic disorders. Increased visceral adipose tissue promotes adipokine dysregulation and insulin resistance, leading to several health issues, including systemic inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system. Moreover, an increase in adipose tissue directly and indirectly affects the kidneys by increasing renal sodium reabsorption, causing glomerular hyperfiltration and hypertrophy, which leads to increased proteinuria and kidney fibrosis/dysfunction. Although the interest in the adverse effects of obesity on renal diseases has grown exponentially in recent years, the relationship between obesity and renal prognosis remains controversial. This may be attributed to the long clinical course of obesity, numerous obesity-related metabolic complications, and patients’ attributes. Multiple individual attributes influencing the pathophysiology of fat accumulation make it difficult to understand obesity. In such cases, it may be effective to elucidate the pathophysiology by conducting research tailored to individual attributes from the perspective of attribute-based medicine/personalized medicine. We consider the appropriate use of clinical indicators necessary, according to attributes such as chronic kidney disease stage, level of visceral adipose tissue accumulation, age, and sex. Selecting treatments and clinical indicators based on individual attributes will allow for advancements in the clinical management of patients with obesity and chronic kidney disease. In the clinical setting of obesity-related nephropathy, it is first necessary to accumulate attribute-based studies resulting from the accurate evaluation of visceral fat accumulation to establish evidence for promoting personalized medicine.

Mineral bone disorder (MBD) is a frequent consequence of chronic kidney disease, more so in patients with kidney failure treated by kidney replacement therapy. Despite the wide availability of interventions to control serum phosphate and parathyroid hormone levels, unmet gaps remain on optimal targets and best practices, leading to international practice pattern variations over time. In this Special Report, we describe international trends from the Dialysis Outcomes and Practice Patterns Study (DOPPS) for MBD biomarkers and treatments from 2002-2021, including data from a group of 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom), Japan, and the United States. From 2002-2012, mean phosphate levels declined in Japan (5.6 to 5.2 mg/dL), Europe (5.5 to 4.9 mg/dL), and the United States (5.7 to 5.0 mg/dL). Since then, levels rose in the United States (to mean 5.6 mg/dL, 2021), were stable in Japan (5.3 mg/dL), and declined in Europe (4.8 mg/dL). In 2021, 52% (United States), 27% (Europe), and 39% (Japan) had phosphate >5.5 mg/dL. In the United States, overall phosphate binder use was stable (80%-84% over 2015-2021), and parathyroid hormone levels rose only modestly. Although these results potentially stem from pervasive knowledge gaps in clinical practice, the noteworthy steady increase in serum phosphate in the United States over the past decades may be consequential to patient outcomes, an uncertainty that hopefully will soon be addressed by ongoing clinical trials. The DOPPS will continue to monitor international trends as new interventions and strategies ensue for MBD management in chronic kidney disease.

Abstract IgA nephropathy (IgAN) patients often suffer from arterial and/or arteriolar sclerosis (AAS); however, it is unclear whether these features are associated with a poor prognosis. This retrospective cohort study aimed to analyse the prognosis of IgAN patients with AAS and assess whether treatment with renin–angiotensin system inhibitors (RASI) improved their survival. The study included 678 IgAN patients, who were grouped into AAS0 (n = 340; AAS absent) and AAS1 (n = 338; AAS present) groups. Each patient's clinical, laboratory, and histological backgrounds and 20‐year renal prognosis were analysed. In the AAS1 group, the impact of RASI initiated during the follow‐up period on the renal prognosis was also evaluated after adjustments for background characteristics. IgAN patients with AAS had significantly higher age, blood pressure, body mass index, total cholesterol, uric acid levels, and proteinuria than patients without AAS; they also had more severe histological findings, decreased renal function, and lower survival rates than those without AAS (64.0 versus 84.7%, p

Mycobacterium abscessus subsp. abscessus (MABA) is refractory and sometimes fatal especially in an immunocompromised patient. Also, MABA-associated pneumothorax is an extremely rare complication. We report a case of MABA pulmonary infection complicated pneumothorax treated successfully. A 69-year-old Japanese female with immunosuppressed systemic sclerosis-associated interstitial lung disease experienced left-sided secondary spontaneous pneumothorax. MABA was detected in the pleural effusion and blood culture. Microbial sensitivity test showed the MABA was sensitive to only amikacin, sitafloxacin, and clofazimine. Combination therapy with these antibiotics including azithromycin achieved remission within three weeks. In the treatment of MABA infection, compliance with microbial sensitivity test is crucial.

Abstract A target Kt/V of > 1.4 and use of a high-flux dialyzer are recommended for patients on hemodialysis. However, there is little information on the relationship between the dialyzer surface area and mortality in these patients. In this nationwide cohort study, we aimed to clarify this relationship by analyzing data from the Japanese Society for Dialysis Therapy for 2010–2013. We enrolled 234,638 patients on hemodialysis who were divided according to quartile for dialyzer surface area into the S group (small,

Background Screening for intracranial aneurysms (IAs) in patients with risk factors of IA is recommended. However, genetic risk factors of IA in patients with autosomal dominant polycystic kidney disease (ADPKD) remain unclear, and genotype–phenotype relationships in IAs in patients with ADPKD have not been clarified. Therefore, we aimed to clarify the associations between germline mutations and IA formation in patients with ADPKD. Methods A total of 135 patients with ADPKD who were evaluated for ADPKD mutations were examined for IA formation in this single‐center observational study. Results The incidence of de novo IA formation was 1.3% per patient‐year. Age at IA diagnosis was younger in patients with frameshift (median, 36 years; P=0.003) and splicing mutations (median, 43 years; P=0.046) than in patients with substitutions (median, 63 years). Multivariable analyses showed that IA was associated with female sex (odds ratio [OR], 3.32 [95% CI, 1.10–10.01]; P=0.03), a family history of IA or subarachnoid hemorrhage (OR, 3.05 [95% CI, 1.07–8.71]; P=0.04), estimated glomerular filtration rate (OR, 0.69 [95% CI, 0.54–0.87]; P=0.002), and splicing mutations (OR, 9.30 [95% CI, 1.71–50.44]; P=0.01). Splicing mutations showed a significant association with IA formation even in subcohorts with minimal risk factors for IA, such as age

Abstract According to the annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) conducted at the end of 2018, there were a total of 339,841 patients receiving dialysis (hereinafter, dialysis patients) in Japan. The survey included questions regarding the presence/absence of dementia, the performance status (PS), and the exercise habits of individual patients. The survey revealed that 10.8% of all dialysis patients had dementia (1.8% in the age group of less than 65 years, 6.8% in the age group of 65–74 years, and 22.7% in the age group of 75 years or older). These prevalences of dementia were approximately equal to those estimated from the survey conducted in 2010. Regarding PS, the percentage of patients with lower activity levels tended to be relatively high among patients who were less than 15 years old and those who were 60 years old or older. Concerning the exercise habits of dialysis patients, the percentage of patients who were classified as “not at all or hardly” in response to the question about exercise habit was the highest (60–80%) of all the exercise habit classifications in each of the age groups analyzed.

Abstract Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on β2-microglobulin clearance rates of

Abstract Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are prescribed as conservative or adjunctive therapies for adult idiopathic nephrotic syndrome. However, studies on real‐world practice patterns are scarce. This study aimed to examine the prevalence and incidence of ACEI/ARB prescription and their associated factors. This nationwide cohort study included adult Japanese patients with idiopathic nephrotic syndrome including minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and others. The outcomes were the prevalence of ACEI/ARB prescription at baseline (date of renal biopsy or date of immunosuppressant initiation) and at 2 months after baseline. Of the 326 eligible patients, 122 (37.4%) had already been prescribed ACEIs/ARBs. Of the remaining 204 patients, 67 (32.7%) were newly prescribed within the 2‐month period. MN/FSGS (vs. MCD, adjusted odds ratio [AOR]: 4.96 [95% confidence interval {CI} 2.53–9.72] and 3.95 [95% CI 1.61–9.66], respectively), higher age (per 1‐yr increase, AOR: 1.02 [95% CI 1.00–1.04]), other hypertensive agents (AOR: 2.18 [95% CI 1.21–3.92]), antidiabetic drug (AOR: 6.57 [95% CI 1.77–24.4]) were associated with a higher prevalence of ACEI/ARB prescription. MN (vs. MCD, AOR: 6.00 [95% CI 2.57–14.0]) and higher baseline systolic blood pressure (SBP) (per 10‐mmHg increase, AOR: 1.36 [95% CI 1.09–1.70]) were associated with a higher incidence of ACEI/ARB prescription. On average, incidence of ACEI/ARB prescription increased from 19.2% to 40.8% as baseline SBP increased from 100 to 140 mmHg. Thus, Japanese nephrologists are likely to prescribe ACEIs/ARBs for nephrotic patients with MN or high baseline SBP, even below the hypertensive range.

Abstract According to the annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) conducted at the end of 2018, a total of 339,841 patients were receiving dialysis (hereinafter, dialysis patients) in Japan. This survey included an investigation of individual test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCV-Ab), HCV-RNA, and serum alanine aminotransferase (ALT) (glutamic pyruvic transaminase [GPT]). The survey revealed that among dialysis patients in Japan, the prevalence of HBsAg positivity was 1.38% and the prevalence of HCV-Ab positivity was 4.7% at the end of 2018, both of which were markedly lower than the corresponding rates documented in 2007 (9.8% and 4.7%, respectively). The proportion of HCV-RNA-positive patients among all HCV-Ab-positive patients was 37.5%, which was also markedly lower than the percentage recorded in 2007 (64.0%). The prevalence of HBsAg positivity tended to increase as the dialysis vintage increased. The prevalence of HCV-Ab positivity was also not correlated with the dialysis vintage during the first 30 years of dialysis; however, it tended to increase as the dialysis vintage increased beyond the 30th year. Trial registration University hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000018641 . The JRDR was approved by the ethics committee of the JSDT (approval number 1-3) and was registered on August 8, 2015 (accessed June 2, 2020).

Abstract Background Intradialytic hypotension (IDH) is one of the most frequent complications of hemodialysis. IDH alters a patient’s quality of life and has a strong association with mortality. IDH mainly occurs when ultrafiltration during hemodialysis exceeds the pace of the plasma refill. Ultrasonography has been used to evaluate the intravascular volume status. We evaluated the association between IDH and baseline laboratory data or ultrasound findings during IDH during the latter half of a hemodialysis session. Methods Sixty-two patients who underwent hemodialysis were enrolled in this study. The peak early mitral inflow wave velocity (peak E-velocity), the inferior vena cava (IVC) dimensions, and number of B-lines were estimated at two time points (just after the start and at the midpoint of the hemodialysis session). We compared the parameters between the patients without IDH throughout the hemodialysis session (non-IDH group) and patients with IDH only during the latter half of the hemodialysis session (IDH in the latter half group). Results Of the 62 study participants, 28 patients were in non-IDH group, and 16 patients were in IDH in the latter half group. The serum sodium level was significantly lower in the IDH in the latter half group (135 ± 4 mEq/L) than in the non-IDH group (138 ± 4 mEq/L) (P = 0.015). The rate of decrease of the peak E-velocity was significantly higher in the IDH in the latter half group (0.33 ± 0.13) than in the non-IDH group (0.24 ± 0.14) (P = 0.037). The best cutoff point of the serum level of sodium was 137 mEq/L, with a sensitivity of 68.8% and specificity of 64.3%. The area under the receiver operating characteristic (ROC) curve was 0.71. The best cutoff point of the rate of decrease of the peak E-velocity was 0.295, with a sensitivity of 73.3% and a specificity of 71.4%. The area under the ROC curve was 0.71. Conclusions A low serum level of sodium at baseline and an early decrease in the peak E-velocity during hemodialysis may be related to intradialytic hypotension in the latter half of a hemodialysis session. Careful observation may be needed in the hemodialysis patients in whom the serum level of sodium is below 137 mEq/L or the rate of decrease of the peak E-velocity is over 0.295.

Abstract The Oxford classification of IgA nephropathy (IgAN) can evaluate each MEST-C score individually. We analysed a new grading system that utilised the total MEST-C score in predicting renal prognosis. Altogether, 871 IgAN patients were classified into three groups using the new Oxford classification system (O-grade) that utilised the total MEST-C score (O-grade I: 0–1, II: 2–4, and III: 5–7 points), and the 10-year renal prognosis was analysed. The clinical findings became significantly severer with increasing O-grades, and the renal survival rate by the Kaplan–Meier method was 94.1%, 86.9%, and 74.1% for O-grades I, II, and III, respectively. The hazard ratios (HRs) for O-grades II and III with reference to O-grade I were 2.8 (95% confidence interval [CI] 1.3–6.0) and 6.3 (95% CI 2.7–14.5), respectively. In the multivariate analysis, mean arterial pressure and eGFR, proteinuria at the time of biopsy, treatment of corticosteroids/immunosuppressors, and O-grade (HR 1.63; 95% CI 1.11–2.38) were the independent factors predicting renal prognosis. Among the nine groups classified using the O-grade and Japanese clinical-grade, the renal prognosis had an HR of 15.2 (95% CI 3.5–67) in the severest group. The O-grade classified by the total score of the Oxford classification was associated with renal prognosis.

Abstract Background Peritoneal dialysis (PD) is associated with various complications, some of which may result in its discontinuation. Pleuroperitoneal communication (PPC) is commonly recognized by the presence of a diaphragmatic defect and pressure elevation in the abdominal cavity due to the dialysate. PPC is unpredictable and its presence prevents the continuation of PD. We present the clinical course and pathological findings of PPC in a PD patient after bacterial peritonitis and total gastrectomy for gastric neuroendocrine tumors. We provide a brief review of PD-related complications that develop due to a non-infectious pathology, including those related to catheter use and an elevated intra-abdominal pressure. Case presentation A 65-year-old Japanese man, who had been receiving PD treatment for 1 year, visited our hospital owing to a cloudy dialysate. Bacteria were detected in the dialysate. He had been previously diagnosed with gastric neuroendocrine tumors and gastrectomy had been planned. On admission, we started a 14-day antibiotic treatment for PD-related peritonitis. The patient showed a good clinical course. Gastrectomy was performed as planned, and the postoperative course was uneventful. During the perioperative period, PD was temporally changed to hemodialysis. Five weeks after the gastrectomy, PD treatment was resumed with gradual increase in the exchange volume. After returning to PD overnight, using an automated peritoneal dialysis machine, the patient complained of breathing difficulty and he gained weight. Right-sided pleural effusion was observed on a chest radiograph, and PPC was confirmed by scintigraphy when a mixture of technetium-99m and dialysate was seen entering the right hemithorax within 120 min. The patient did not consent to surgery for the PPC and he hoped to continue to receive PD treatment conservatively. We advised the patient to undergo dialysate exchange in a semi-seated position, and he was prohibited from lying down during the daytime. He continued PD treatment without signs of pleural effusion and over-volume. Conclusions This case of PPC occurring after bacterial peritonitis and total gastrectomy for gastric neuroendocrine tumors in a PD patient demonstrates the necessity of recognizing the PPC pathology in PD management and establishing methods for preventing PPC development after bacterial peritonitis or surgical procedures.

Abstract Background The expected remaining lifetime of dialysis patients in Japan was only reported in 2003 and has not been reported thereafter. From 2003 to the present, several new therapeutic agents have been introduced. These events may have improved outcomes for dialysis patients. Thus, expected remaining lifetime of dialysis patients in Japan was newly calculated in 2015. Methods The Japanese Society for Dialysis Therapy Renal Data Registry database was used for analyses. From this database, the following three indexes were compiled: the number of surviving dialysis patients (198,125 males and 111,962 females) at the end of 2014 and the number of surviving (179,649 males and 101,758 females) and dead (18,044 males and 111,417 females) patients at the end of 2015. Based on these values, expected remaining lifetime at 1-year increment was calculated using the life table method. Results Excerpts of the calculated expected remaining lifetimes of patients aged 60 years were as follows: 11.9 years for males and 14.1 years for females. These expected remaining lifetimes were 1.1 to 1.2 times as compared with those in 2003. Meanwhile, expected remaining lifetime of diabetic patients was 10.8 years for males and 12.5 years for females and that of nondiabetic patients was 13.0 years for males and 15.0 years for females. Conclusion Expected remaining lifetime of dialysis patients in Japan in 2015 was 10–20% longer than that in 2003. These results suggest that advances in dialysis technologies during this 12-year period improved the survival rate of dialysis patients.

Abstract The annual survey questionnaires of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) were sent to 4458 dialysis facilities at the end of 2018; 4402 facilities (98.7%) responded to the facility questionnaire, and 4222 facilities (94.7%) responded to the patient questionnaire. This paper reports the results obtained in regard to several issues: dialysis fluid quality, prescription of hemodialysis and hemodiafiltration, current status of peritoneal dialysis, and glycemic indices and treatment of diabetic patients.

Abstract Background BK polyomavirus (BKPyV) infection after kidney transplantation is an important cause of graft failure among kidney transplant recipient and may cause malignant tumor, although the association between BKPyV infection and malignant tumor has been controversial yet. Case presentation We report a case of a 39-year-old-male kidney transplantation (KTx) recipient with urine BKPyV replication who developed a graft pelvic tumor with the positive Simian virus 40 large T antigen (SV40 TAg). The patients received a living-related KTx from his 65-year-old mother. A protocol biopsy at 14 months after KTx showed BKPyV-associated nephropathy. Therefore, the dose of immunosuppressants was reduced, resulting in improved BKPyV viremia, but viruria persisted. About 117 months after KTx, urine cytology showed atypical cells suspicious for malignancy. Cystoscopy revealed a tumor on the neck of the bladder. Transurethral resection of the bladder tumor (TUR-BT) was performed; however, the diagnosis of malignancy was not confirmed at that time. Six months after the TUR-BT, urine cytology showed atypical cells definite for malignancy. Computed tomography and retrograde pyelography showed no evidence of urinary tract tumor and metastasis. Subsequently, total nephroureterocystectomy and urethrectomy were performed. Histological examination of the graft ureter revealed a high-grade urothelial carcinoma, with glandular differentiation, pT1. Immunohistochemically, the tumor showed positivities for SV40 TAg and p53, along with increased Ki67 labeling cells were increased. By contrast, nonneoplastic cells were negative for SV40 TAg. At the time of writing the present manuscript, the patient is free from recurrence or residual tumor and being closely monitored without additional therapy, 32 months after the surgery. Conclusion The relationship between BKPyV infection after KTx and bladder carcinogenesis remains to be elucidated. However, when the KTx recipients who continue to have BKPyV infection for a long time are treated, the possibility of risk factors for renourinary carcinoma should always be carefully considered.

Abstract The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was sent to 4458 dialysis facilities at the end of 2018; among these facilities, 4402 facilities (98.7%) responded to the facility questionnaire, and 4222 (94.7%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year; as of the end of 2018, it had reached 339,841 patients, representing 2688 patients per million population. Among the prevalent dialysis patients, the mean age was 68.75 years, and diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (26.8%) and nephrosclerosis (10.8%). The number of incident dialysis patients was 40,468, and a reduction by 491 from 2017. The mean age of the incident dialysis patients was 69.99 years old. Diabetic nephropathy was also the most common primary disease (42.3%), representing a 0.2 percent point reduction from 2017. The distribution of diabetic nephropathy appears to have reached a plateau. The number of deceased patients during 2018 was 33,863, and the crude annual death rate was 10.0%. Heart failure was the most common cause of death (23.5%), followed by infection (21.3%) and malignant tumor (8.4%); these causes were similar to those for 2017. The number of patients receiving hemodiafiltration has been increasing since 2012, reaching 125,793 or 37.0% of all dialysis patients at the end of 2018. The number of patients receiving peritoneal dialysis has been gradually increasing since 2017, reaching 9445, and 19.7% of these patients were treated using a combination of peritoneal dialysis and hemodialysis or hemodiafiltration. The proportion of patients receiving combination therapy has remained at around 20% of all peritoneal dialysis patients. The number of patients undergoing home hemodialysis was 720, representing an increase of 36 patients from 2017. The 2018 JRDR survey included several topics such as the present status of the patient kinetics of chronic dialysis patients at the end of 2018, water treatment and hemodiafiltration, peritoneal dialysis, treatments for diabetes, mental and physical conditions, and the present status of viral hepatitis. In this paper, we describe the patient and facility kinetics. Trial registration The JRDR was approved by the ethics committee of the JSDT (approval number 1-3) and was registered in the “University hospital Medical Information Network (UMIN) Clinical Trials Registry” under the clinical trial ID of UMIN000018641 on August 8, 2015: (Accessed June 2, 2020)

During this half a century since immunoglobulin A (IgA) nephropathy was firstly reported in 1968, several clinical and histological grading systems to predict the prognosis have been reported. In Japan, since the first version of clinical guideline for IgA nephropathy was established in 1995, it was revised in 2014 to the third version which was the grading system based on both clinical and histological risk factors. In this report, we have shown the details and evaluation of clinical grading system of that Japanese guideline, and also shown the previous reported clinical grading system.This report is secondary publication of previous our review report "Nippon Rinsho 77: 643-650, 2019".

Background Higher serum β2-microglobulin (B2M) concentrations are associated with higher mortality in the general population, non-dialyzed chronic kidney disease patients and patients receiving hemodialysis (HD). However, this relationship among patients on peritoneal dialysis (PD) has not been validated. Methods We collected baseline data for 3,011 prevalent PD patients from a nationwide dialysis registry in Japan at the end of 2010. Clinical outcomes for 9 years were then evaluated using the registry at the end of 2011 to 2019. All-cause and cardiovascular (CV) mortality was assessed using Cox regression analysis and competing-risks regression analysis, respectively. We used multiple imputation to deal with missing covariate data. Results During a median follow-up of 87 months, 2,054 patients transferred to combined therapy with PD and HD or HD directly. A total of 3,011 patients, 1,235 (41.0%) died, including 437 patients (14.5%) from CV causes. Among them, 612 patients died after transfer to other dialysis modalities. Univariate analyses revealed no significant association between serum B2M and mortality, whereas higher serum B2M was independently associated with both all-cause and CV mortalities in adjusted models. However, the significant association between serum B2M and CV mortality disappeared in analysis treating serum B2M as a categorical variable. The effect of serum B2M on all-cause mortality was significantly higher among patients with higher urinary volume and a significant interaction was evident. Conclusions Using a large-scale registry, we found that serum B2M contributes tenuously but significantly to worse outcome and residual kidney function significantly affects this relationship. On the contrary, serum B2M per se had no predictive value for patient outcome in prevalent PD patients.

Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA) typically occurs in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive cases presenting with rapidly progressive renal insufficiency and urinary abnormalities induced by primarily necrotizing crescentic glomerulonephritis (NCGN). Recently, ANCA-negative EGPA has also been reported to manifest with renal involvement, such as NCGN or non-NCGN, including membranous nephropathy (MN). Herein, we report a 70-year-old female who presented with purpura on the lower legs, upper limb numbness, renal dysfunction (eGFR, 20.5 ml/min/1.73 m2), and eosinophilia (eosinophils, 37,570/μl). MPO-and PR3-ANCA were negative, and urinalysis revealed urine protein (0.63 g/day) but without red blood cells in the urine sediment. Thus, she was diagnosed with ANCA-negative EGPA with rapidly progressive renal dysfunction. A renal biopsy revealed vasculitis in the interlobular arteries without NCGN, with the vasculitis being complicated by MN. Micrograph findings on fluorescence immunostaining contained both primary and secondary characteristics of MN (dominance of IgG subclass 4 more than subclass 1 vs. negativity of PLA2R and THSD7A). After treatment with prednisolone, her eosinophil counts normalized, and renal dysfunction improved. Furthermore, urine protein did not increase above 1.0 g/day during the clinical course. This is a rare case of ANCA-negative EGPA presenting with acute renal dysfunction without NCGN and subclinical MN with unknown etiology. It is important to recognize that EGPA pathology varies widely throughout the disease course, and the clinical course of subclinical MN should be carefully assessed in further follow-ups.

Background. The importance of crescent formation in glomerulonephritis has increased. However, detailed analysis of crescentic glomerulonephritis in Asia is scarce. In addition, advances in serological diagnostic techniques (antineutrophil cytoplasmic and antiglomerular basement membrane autoantibodies) and early diagnosis have reduced the number of cases meeting the strict definition of crescentic glomerulonephritis (>50% of glomeruli are crescentic). Therefore, we analyzed the clinicopathological features and renal prognosis of glomerulonephritis cases that exhibited at least one crescentic lesion. Methods. We retrospectively evaluated 265 adult patients diagnosed with glomerulonephritis with at least one crescent formation based on the results of renal biopsy. We divided the patients into two groups based on the four types of glomerulonephritis, namely, the immune-complex (type II: IgA nephropathy, IgA vasculitis with nephritis, and lupus nephritis) and pauci-immune (type III: microscopic polyangiitis) groups. Factors affecting renal prognosis (end-stage renal failure requiring renal replacement therapy) were examined in a multivariate analysis using the Cox proportional hazards model. Kaplan–Meier curves and log-rank test were used to analyze and compare time from entry to renal death. Results. Renal prognosis differed significantly between the immune-complex and pauci-immune groups. Among the four types of glomerulonephritis, IgA nephropathy was the most prevalent. Multivariate analysis showed that renal function at renal biopsy and the ratio of global sclerosis independently predicted renal prognosis, but the type of glomerulonephritis was not a factor. Conclusions. Renal dysfunction at renal biopsy and the ratio of global sclerosis predicted renal prognosis, because it reflects the degree of irreversible renal damage. We also suspect that the formation of at least one crescentic lesion led to the development of these predictive factors, regardless of the type of glomerular disease and degree of crescent formation.

Micropetrosis develops as a result of stagnation of calcium, phosphorus and bone fluid, which appears as highly mineralized bone area in the osteocytic perilacunar/canalicular system regardless of bone turnover of the patients. And microcracks are predisposed to increase in these areas, which leads to increased bone fragility. However, micropetrosis of hemodialysis (HD) patients has not been discussed at all. Micropetrosis area per bone area (Mp.Ar/B·Ar) and osteocyte number per micropetrosis area (Ot.N/Mp.Ar) were measured in nine HD patients with renal hyperparathyroidism (Group I), twelve patients with hypoparathyroidism within 1 year after the treatment of renal hyperparathyroidism (Group II) and seven patients suffering from hypoparathyroidism for over two years (Group III). And bone mineral density (BMD) and tissue mineral density (TMD) were calculated using μCT to evaluate bone mineral content of iliac bone of the patients. These parameters were compared among the three groups. Only Mp.Ar/B·Ar was statistically greater in Group II and III compared to Group I in the parameters of bone mineral content and micropetrosis. However, the other parameters were not statistically different among the three groups. In long-term HD patients, BMD and TMD may be modified by the causes of renal insufficiency and the treatment of renal bone disease. We concluded that Mp.Ar/B·Ar was greater in patients with long-term hypoparathyroidism than both those with short-term hypoparathyroidism and with renal hyperparathyroidism. Special attention should be paid to avoid long-term hypoparathyroidism of the patients from the view point of increased fracture risk caused by increased micropetrosis area.

Background: Dialyzers are classified as low-flux, high-flux, and protein-leaking membrane dialyzers internationally and as types I, II, III, IV, and V based on β2-microglobulin clearance rate in Japan. Type I dialyzers correspond to low-flux membrane dialyzers, types II and III to high-flux membrane dialyzers, and types IV and V to protein-leaking membrane dialyzers. Here we aimed to clarify the association of dialyzer type with mortality.Methods: This nationwide retrospective cohort study analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry from 2010 to 2013. We enrolled 238,321 patients on hemodialysis who were divided into low-flux, high-flux, and protein-leaking groups in the international classification and into type I to V groups in the Japanese classification. We assessed the associations of each group with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis.Results: By the end of 2013, 55,308 prevalent dialysis patients (23.2%) had died. In the international classification subgroup analysis, the hazard ratio (95% confidence interval) was significantly higher in the low-flux group [1.12 (1.03–1.22), P = 0.009] and significantly lower in the protein-leaking group [0.95 (0.92–0.98), P = 0.006] compared with the high-flux group after adjustment for all confounders. In the Japanese classification subgroup analysis, the hazard ratios were significantly higher for types I [1.10 (1.02–1.19), P = 0.015] and II [1.10 (1.02–1.39), P = 0.014] but significantly lower for type V [0.91 (0.88–0.94), P < 0.0001] compared with type IV after adjustment for all confounders. These significant findings persisted after propensity score matching under both classifications.Conclusions: Hemodialysis using protein-leaking dialyzers might reduce mortality rates. Furthermore, type V dialyzers are superior to type IV dialyzers in hemodialysis patients.

Abstract Background Hemodialysis patients are prone to constipation, which can adversely affect their quality of life (QOL). Elobixibat, a highly selective inhibitor of the ileal bile acid transporter, can increase the bile acid level in the colon and, subsequently, enhance colonic motility and secretion. In hemodialysis patients with chronic constipation, it may have a novel action mechanism. However, the effect of elobixibat on such patients’ QOL had not been reported. This study aimed to evaluate the effect of elobixibat on the QOL of hemodialysis patients with chronic constipation. Methods This was a multicenter, observational study that used the Japanese version of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaire on 27 patients (18 men and nine women, age range 47–90 years), who satisfied the Rome 3 diagnostic criteria for functional constipation and were already taking other drugs for constipation. These patients were administered elobixibat 10 mg/day and were asked to respond to the PAC-QOL questionnaire at baseline and after 4 weeks. Bayesian statistics were used to confirm our results. Results The number of spontaneous bowel movements per week increased significantly from 2.6 ± 1.2 to 4.1 ± 2.1 (p

Associations between anti-M-type phospholipase A2 receptor (PLA2R) antibodies and disease activity and prognosis have been suggested in primary membranous nephropathy (MN); however, more evidence is needed. We aimed to establish a clinically useful method to measure anti-PLA2R antibodies. We developed a western blot assay and a cell-based enzyme-linked immunosorbent assay (ELISA). Anti-PLA2R antibodies were evaluated retrospectively using these assays and the commercial solid-phase ELISA. Anti-PLA2R antibodies were detected in 12, 6, and 12 out of 23 Japanese patients with biopsy-proven primary MN using the western blot, the cell-based ELISA, and the solid-phase ELISA, respectively. The samples of the lupus MN patients tested negative. The levels of proteinuria correlated moderately with the titres of anti-PLA2R antibodies measured by the three methods (r = 0.39–0.47). Anti-PLA2R antibodies were significantly associated with physicians’ decisions on immunosuppressive treatment without prior knowledge of anti-PLA2R antibody positivity (p

Abstract The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was conducted for 4413 dialysis facilities at the end of 2017; among which 4360 facilities (98.8%) responded to the facility questionnaire, and 4188 (94.9%) responded to the patient questionnaire. The response rate of the 2017 survey was comparable with the past, even though it was the third year after the new anonymization method. The number of chronic dialysis patients in Japan continues to increase every year; it has reached 334,505 at the end of 2017. The mean age was 68.43 years. The prevalence rate was 2640 patients per million population. Diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (27.8%) and nephrosclerosis (10.3%). The rate of diabetic nephropathy and nephrosclerosis has been increasing year by year, whereas that of chronic glomerulonephritis was declining. The number of incident dialysis patients during 2017 was 40,959; it has remained stable since 2008. The average age was 69.68 years and diabetic nephropathy (42.5%) was the most common cause in the incident dialysis patients. These patients caused by diabetes did not change in number for recent several years. Further, 32,532 patients died in 2017; the crude mortality rate was 9.8%. The patients treated by hemodiafiltration (HDF) have been increasing rapidly from the revision of medical reimbursement for HDF therapy in 2012. It has attained 95,140 patients at the end of 2017, which were 18,304 greater than that in 2016. The number of peritoneal dialysis (PD) patients was 9090 in 2017, which had been slightly decreasing since 2014. Further, 19.4% of PD patients treated in the combination of hemodialysis (HD) or HDF therapy (hybrid therapy). And 984 patients were treated by home HD therapy at the end of 2017; it increased by 49 from 2016. Trial registration JRDR was approved by the ethical committee of JSDT (approval number 1-3) and has been registered in “University hospital Medical Information Network (UMIN) Clinical Trials Registry” as a clinical trial ID of UMIN000018641 at 8th August 2015. https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000021578 (Accessed 31 July 2019).

Abstract Renal fibrosis is one of the largest global health care problems, and microvascular (MV) injury is important in the development of progressive fibrosis. Although conventional cell therapy suppresses kidney injury via the role of vasoprotective cytokines, the effects are limited due to low retention of administered cells. We recently described that transplantation of hepatocyte growth factor (HGF)‐transgenic mesothelial cell sheets showed a remarkable cell survival and strong therapeutic effects in a rat renal fibrosis model. Due to the translational hurdles of transgenic cells, we here applied this technique for allogeneic transplantation using rat bone marrow mesenchymal stromal cells (MSCs). MSC sheets were transplanted onto the kidney surface of a rat renal ischemia–reperfusion‐injury model and the effects were compared between those in untreated rats and those receiving intravenous (IV) administration of the cells. We found that donor‐cell survival was superior in the cell sheet group relative to the IV group, and that the cell sheets secreted HGF and vascular endothelial growth factor (VEGF) up to day 14. Transplantation of cell sheets increased the expression of activated HGF/VEGF receptors in the kidney. There was no evidence of migration of transplanted cells into the kidney parenchyma. Additionally, the cell sheets significantly suppressed renal dysfunction, MV injury, and fibrosis as compared with that observed in the untreated and IV groups. Furthermore, we demonstrated that the MSC sheet protected MV density in the whole kidney according to three‐dimensional microcomputed tomography. In conclusion, MSC sheets strongly prevented renal fibrosis via MV protection, suggesting that this strategy represents a potential novel therapy for various kidney diseases. Stem Cells Translational Medicine 2019;8:1330&1341

Alport syndrome is a hereditary glomerular nephritis associated with hearing loss and eye abnormalities and is classified as X-linked Alport syndrome, autosomal recessive Alport syndrome, and autosomal dominant Alport syndrome. Autosomal dominant Alport syndrome is caused by a mutation in the gene encoding type IV collagen α3 (α3[IV]); (COL4A3), or α4 (α4[IV]); (COL4A4). Autosomal dominant Alport syndrome progresses more gradually than male X-linked Alport syndrome and autosomal recessive Alport syndrome. Differentiating autosomal dominant Alport syndrome from thin basement membrane nephropathy, which shows better kidney prognosis, remains challenging. Because autosomal dominant Alport syndrome is linked to a heterozygous mutation, type IV collagen is produced by the wild-type allele, and all α(IV) chains are supposed to be normally expressed. In this study, the pathologic findings of a patient with Alport syndrome with a novel COL4A4 heterozygous nonsense mutation were investigated. We observed weaker staining of α5(IV) in the glomerular basement membrane and enhanced expressions of α2(IV), laminin, and fibronectin, which were assumed to be caused by compensatory mechanisms for lack of enough α3α4α5(IV) expression in the glomerular basement membrane. These findings may be useful not only for differentially diagnosing autosomal dominant Alport syndrome from thin basement membrane nephropathy, but also for determining the extent of progression and predicting kidney prognosis. Index Words: Alport syndrome, autosomal dominant Alport syndrome, thin basement membrane nephropathy, type IV collagen, laminin, fibronectin

Light chain proximal tubulopathy is a rare M-proteinemia–related nephropathy. The inclusions, composed of light chains in light chain proximal tubulopathy, are generally crystalline, and most exhibit a rhombic shape. Noncrystalline structures, such as rods or needle shapes, may also be present. In our patient, one of the noncrystalline structures, fibrillary inclusions in the cytoplasm, were observed, as previously reported in only 4 patients whose primary disease was either multiple myeloma or monoclonal gammopathy of renal significance. This is the first report involving lymphoma. Early diagnosis of light chain proximal tubulopathy is important because those who undergo chemotherapy have an improved kidney prognosis. However, in cases of kidney involvement with blood disorders, thrombocytopenia is often present. Therefore, in our case, open kidney biopsy was selected. Noncrystalline light chain proximal tubulopathy is believed to be less likely to cause Fanconi syndrome. However, Fanconi syndrome was observed in 3 of the 4 patients with fibrillary inclusions. In our case, hypouricemia was improved by chemotherapy, suggesting that the patient presented with Fanconi syndrome. Noncrystalline light chain proximal tubulopathy with fibrillary inclusions may cause Fanconi syndrome, similar to crystalline light chain proximal tubulopathy. We report a case of light chain proximal tubulopathy with fibrillary inclusions complicated by low-grade B-cell lymphoma in which early treatment was successful. Index Words: Light chain proximal tubulopathy, fibrillary inclusion, lymphoma, Fanconi syndrome, hypouricemia, kidney biopsy, monoclonal gammopathy of renal significance (MGRS)

Background/Aims: Cross-classification analyses are rarely reported. We investigated the prognostic factors for chronic kidney disease (CKD) progression using a body mass index (BMI)-based cross-classification approach. Methods: Patients’ renal outcome (≥50% decline in the estimated glomerular filtration rate or end-stage renal disease) in each subcohort was examined. Results: The number of prognostic factors identified in the multivariate Cox analysis was smaller in the “BMI ≥25, female” and CKD stage 3 subcohorts than in other subcohorts. Prognostic factors identified in the “BMI ≥25, CKD stage 3” subcohort only comprised albuminuria and male sex, and those in the “BMI ≥25, female” subcohort only comprised albuminuria, hyperphosphatemia, and anemia. Albuminuria, kidney impairment, male sex, hyperphosphatemia, anemia, and increased pulse pressure × heart rate product (PP × HR; pulsatile stress) were stable renal prognostic factors in almost all subcohorts. On the other hand, the prognostic value of increased BMI, younger age, hypoalbuminemia, increased intact parathyroid hormone, and decreased estimated 24-h urinary potassium excretion (e24hUK) differed according to subcohort. BMI was positively associated with CKD progression in the “BMI ≥25, age ≥65 years” and “BMI ≥25, CKD stages 4–5” subcohorts, whereas it was negatively associated with CKD progression in the “BMI

Abstract Background Volume overload in hemodialysis patients is an independent risk factor for cardiovascular event-related mortality. The number of B-lines observed using lung ultrasound is correlated with the severity of pulmonary congestion. The aim of this study was to evaluate the association between the number of B-lines and mortality among hemodialysis patients. Methods A total of 61 patients receiving maintenance hemodialysis were enrolled in this study. Clinical data including age, sex, duration of hemodialysis therapy, presence of diabetes mellitus and/or hypertension and/or dyslipidemia complications, the results of biological examinations, and outcome were collected from the patients’ clinical records. We performed echographic examinations at three time points (just after the start, during the middle, and just before the end of hemodialysis therapy). A univariate Cox proportional hazard model was used to identify predictors of the overall outcomes. Furthermore, we divided patients into two groups according to the median number of the B-lines at the end of dialysis and compared the mortality between the two groups. Results The mean follow-up period was 507 ± 385 days. During the follow-up period, 24 deaths were recorded. Predictive variables for mortality included age; serum level of albumin, creatinine, and N-terminal pro-brain natriuretic peptide; and body weight (P

Abstract Since 2015, the Committee for International Communication on Academic Research of the Japanese Society for Dialysis Therapy has held its Asian symposium during the society’s Annual Congress to discuss the present status of and demand for dialysis therapy in Asian countries in order to identify needs and find ways to contribute to these countries in the area of dialysis therapy. Five manuscripts are presented here by symposium participants from Cambodia, Laos, Bhutan, Mongolia, and Indonesia from the Asian symposium of 2016. With progress in economic development, hemodialysis (HD) therapy has now been introduced in all countries worldwide. However, the cost of HD is extremely high compared with typical incomes in every country, and as of 2016, many countries still have not established national health insurance systems. In Cambodia and Laos, for example, patients must bear 100% of the cost for dialysis. In contrast, in Bhutan, the government bears all costs and the patients need not pay at all. In Mongolia and Indonesia, dialysis is almost completely covered by national health insurance. Dialyzers tend to be reused in Cambodia, Laos, and Indonesia. In Mongolia and Bhutan, dialyzers are single-use only. Continuous ambulatory peritoneal dialysis is available in Mongolia and Indonesia but is just starting to be introduced in Laos; it is not available in Cambodia and Bhutan. In Cambodia and Laos where there is no national health insurance system, patients with lower socioeconomic status come to the HD center only when they have enough money to pay for an HD session. Viable health insurance systems should be established as soon as possible. However, this will ultimately depend on the countries’ economic development.