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Background The associations of focal segmental glomerulosclerosis (FSGS) histological variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. Methods Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end-stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression and proteinuria remission (PR; proteinuria Results The distribution of variants was 48% (n = 145) FSGS not otherwise specified, 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants [hazard ratio adjusted for histological variant and potential confounders (adjusted HR) 0.19 (95% confidence interval 0.10–0.34)]. NS was marginally associated with better outcome compared with non-NS [adjusted HR 0.50 (95% confidence interval 0.25–1.01)]. Conclusions FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.

Although a substantial number of patients return to dialysis after kidney transplant failure, it remains controversial whether transplant-failure patients have a higher mortality risk than transplant-naive patients on dialysis who have never undergone kidney transplantation. We compared outcomes of transplant-failure and transplant-naive patients on hemodialysis. Data from the Japanese National Dialysis Registry (2012–2013) were analyzed, including 220,438 prevalent hemodialysis patients. Multivariable Cox models were used to compare all-cause, cardiovascular, and infection-related mortality during 1-year follow-up between transplant-failure and transplant-naive patients. Multiple imputation and propensity score matching were utilized as sensitivity analyses. During 209,377 patient-years of follow-up, 18,648 all-cause deaths (8.5% of all patients), 7700 cardiovascular deaths (41% of all-cause deaths), and 3806 infection-related deaths (20% of all-cause deaths) were observed. Adjusted hazard ratios [95% confidence intervals] for all-cause, cardiovascular, and infection-related deaths among transplant-failure patients were 0.81 [0.59–1.11], 0.54 [0.30–0.98], and 1.54 [0.92–2.59], respectively. Sensitivity analyses using multiple imputation and propensity score matching yielded similar results. This Japanese cohort study suggested that a cardiovascular mortality risk of transplant-failure patients could be significantly lower than that of transplant-naive patients, while there might be a trend toward a higher infection-related mortality risk in transplant-failure patients. However, this retrospective, single-country study can introduce an immortal time bias in transplant-failure patients, and limit the external validity. Further prospective studies are warranted to improve the comparability of outcomes between transplant-failure and transplant-naive patients, and to examine worldwide the generalizability of the potential cardiovascular benefit of kidney transplantation even after returning to dialysis.

Although a substantial number of patients return to dialysis after kidney transplant failure, it remains controversial whether transplant-failure patients have a higher mortality risk than transplant-naïve patients on dialysis who have never undergone kidney transplantation. We compared outcomes of transplant-failure and transplant-naïve patients on hemodialysis.Data from the Japanese National Dialysis Registry (2012-2013) were analyzed, including 220,438 prevalent hemodialysis patients. Multivariable Cox models were used to compare all-cause, cardiovascular, and infection-related mortality during 1-year follow-up between transplant-failure and transplant-naïve patients. Multiple imputation and propensity score matching were utilized as sensitivity analyses.During 209,377 patient-years of follow-up, 18,648 all-cause deaths (8.5% of all patients), 7700 cardiovascular deaths (41% of all-cause deaths), and 3806 infection-related deaths (20% of all-cause deaths) were observed. Adjusted hazard ratios [95% confidence intervals] for all-cause, cardiovascular, and infection-related deaths among transplant-failure patients were 0.81 [0.59-1.11], 0.54 [0.30-0.98], and 1.54 [0.92-2.59], respectively. Sensitivity analyses using multiple imputation and propensity score matching yielded similar results.This Japanese cohort study suggested that a cardiovascular mortality risk of transplant-failure patients could be significantly lower than that of transplant-naïve patients, while there might be a trend toward a higher infection-related mortality risk in transplant-failure patients. However, this retrospective, single-country study can introduce an immortal time bias in transplant-failure patients, and limit the external validity. Further prospective studies are warranted to improve the comparability of outcomes between transplant-failure and transplant-naïve patients, and to examine worldwide the generalizability of the potential cardiovascular benefit of kidney transplantation even after returning to dialysis.

Background and Aims In IgA nephropathy (IgAN), mesangial IgA deposition activates the complement systems and amplifies the local inflammation, resulting in renal injuries. Although previous studies based on repeat biopsies suggested that the change of MEST-C scores of Oxford classification might be related to the prognosis, there have been few reports about immunofluorescence (IF) changes in repeat biopsies. In this study, we aimed to elucidate the relationship between the changes in the degree of glomerular IgA and C3 depositions and clinical prognosis of IgAN based on repeat biopsy observation. Method Fifty-five patients with IgAN who underwent repeat biopsies at our hospital between 2000 and 2019 were analyzed retrospectively. IF staining in each case was graded with a semiquantitative scale from 0 to 3 (0, negative; 1, weak; 2, moderate; 3, strong staining). MEST-C scores of the Oxford classification were also evaluated. When each score of IF staining or MEST-C in second biopsy was less compared with that in the first biopsy, it was regarded as “improved”. The primary outcome was the time to achieve complete remission (CR), which is defined as disappearance of both urinary protein (UP) ( Results Twenty-seven patients (48%) were male. At the first biopsy, median age and eGFR were 38.5 years (Interquartile ratio (IQR) 17-49) and 92 mL/min/1.73 m2 (IQR 63-108). Median urinary protein creatinine ratio was 0.6 g/gCr (IQR 0.3-1.7) and 45 patients (80%) had microhematuria. Thirty-three patients (59%) were treated by renin angiotensin system inhibitors and forty-three patients (78%) were treated by immunosuppressive therapy. Median period between the two biopsies was 36 months (IQR 25-55). Median IF scores of glomerular IgA and C3 were 2 (IQR 2-3) and 2 (IQR 1-2) in the first biopsies and 2 (IQR 1-2) and 1 (IQR 1-2) in the second biopsies, respectively. During the median 55 months (IQR 17-99) follow up period, disappearance of UP and microhematuria were observed in 47 (84%) and 36 (64%). Thirty-three (59%) patients reached CR. Improvement of the degree of C3 deposition between two biopsies was significantly associated with CR (Hazard ratio (HR) 0.37; 95% confidential interval (CI) 0.17-0.80, p=0.012), while that of IgA deposition had no association (HR 057; CI 0.27-1.19, p=0.125). Improvement of the degree of C3 deposition was also significantly associated with disappearance of microhematuria (HR 0.45; 95%CI 0.24-0.86, p=0.016), but not with disappearance of UP (HR 0.60; 95%CI 0.34-1.2, p=0.15). Multivariate linear regression revealed that the rate of eGFR decline was not related to IF scores. Any of the Oxford classification scores were not associated with these outcomes. Conclusion Attenuation of glomerular C3 deposition is associated with CR. This suggest that C3 deposition, rather than IgA deposition, may be related with the clinical prognosis of IgAN.

Background and Aims The nephron number is thought to be associated with clinical outcomes of chronic kidney disease (CKD). If the nephron number can be estimated in a clinical setting, it could become a strong tool to predict the outcomes. This preliminary study estimated nephron number in CKD patients, and examined the relationship between the nephron number and patient characteristics. Method Data from a multicenter study of the National Hospital Organization of Japan were analyzed, including 565 CKD patients aged over 14 years who underwent a kidney biopsy. The nephron number was estimated by the glomerular density in biopsy specimens and the renal cortex volume. The renal cortex volume was calculated by the previously established equation using ultrasound measurement of the kidney. Linear regression models were used to investigate the associations of the nephron number separately with age, sex, and estimated glomerular filtration rate (eGFR). Results A total of 50% of the patients were women, and the mean (±SD) age of the patients was 51±19 years. The mean eGFR was 63±32 ml/min/1.73m2, and the mean estimated number of non-sclerotic nephrons was 660,000±320,000 per kidney. A larger number of estimated nephron number was associated with younger age, male sex, and higher eGFR. Conclusion To the best of our knowledge, this was the first study to estimate the renal cortex volume and nephron number of CKD patients in the general clinical setting. The results from this study should provide powerful tools for nephrologists in routine clinical practice. Further investigations will be needed to verify the associations between the nephron number and clinical outcomes of CKD patients.

Background Practice patterns and bleeding complications of percutaneous native kidney biopsy (PNKB) have not recently been investigated and the Japanese Society of Nephrology performed a nationwide questionnaire survey in 2018. Methods The survey consisted of nine sections about PNKB: (1) general indications; (2) indications for high-risk patients; (3) informed consent; (4) pre-biopsy evaluation; (5) procedures; (6) sedation; (7) post-biopsy hemostasis, bed rest, and examinations; (8) bleeding complications; and (9) specimen processing. A supplementary survey examined bleeding requiring transcatheter arterial embolization (TAE). Results Overall, 220 directors of facilities (nephrology facility [NF], 168; pediatric nephrology facility [PF], 52) completed the survey. Indications, procedures, and monitoring protocols varied across facilities. Median lengths of hospital stay were 5 days in NFs and 6 days in PFs. Gauge 14, 16, 18 needles were used in 5%, 56%, 33% in NFs and 0%, 63%, 64% in PFs. Mean limits of needle passes were 5 in NFs and 4 in PFs. The bed rest period was 16–24 h in 60% of NFs and 65% of PFs. Based on 17,342 PNKBs, incidence rates of macroscopic hematuria, erythrocyte transfusion, and TAE were 3.1% (NF, 2.8%; PF, 6.2%), 0.7% (NF, 0.8%; PF, 0%), and 0.2% (NF, 0.2%; PF, 0.06%), respectively. Forty-six percent of facilities processed specimens all for light microscopy, immunofluorescence, and electron microscopy, and 21% processed for light microscopy only. Timing of bleeding requiring TAE varied among PNKB cases. Conclusion Wide variations in practice patterns of PNKB existed among facilities, while PNKBs were performed as safely as previously reported. Electronic supplementary material The online version of this article (10.1007/s10157-020-01869-w) contains supplementary material, which is available to authorized users.

Background Practice patterns and bleeding complications of percutaneous native kidney biopsy (PNKB) have not recently been investigated and the Japanese Society of Nephrology performed a nationwide questionnaire survey in 2018. Methods The survey consisted of nine sections about PNKB: (1) general indications; (2) indications for high-risk patients; (3) informed consent; (4) pre-biopsy evaluation; (5) procedures; (6) sedation; (7) post-biopsy hemostasis, bed rest, and examinations; (8) bleeding complications; and (9) specimen processing. A supplementary survey examined bleeding requiring transcatheter arterial embolization (TAE). Results Overall, 220 directors of facilities (nephrology facility [NF], 168; pediatric nephrology facility [PF], 52) completed the survey. Indications, procedures, and monitoring protocols varied across facilities. Median lengths of hospital stay were 5 days in NFs and 6 days in PFs. Gauge 14, 16, 18 needles were used in 5%, 56%, 33% in NFs and 0%, 63%, 64% in PFs. Mean limits of needle passes were 5 in NFs and 4 in PFs. The bed rest period was 16–24 h in 60% of NFs and 65% of PFs. Based on 17,342 PNKBs, incidence rates of macroscopic hematuria, erythrocyte transfusion, and TAE were 3.1% (NF, 2.8%; PF, 6.2%), 0.7% (NF, 0.8%; PF, 0%), and 0.2% (NF, 0.2%; PF, 0.06%), respectively. Forty-six percent of facilities processed specimens all for light microscopy, immunofluorescence, and electron microscopy, and 21% processed for light microscopy only. Timing of bleeding requiring TAE varied among PNKB cases. Conclusion Wide variations in practice patterns of PNKB existed among facilities, while PNKBs were performed as safely as previously reported.

The effectiveness of exercise in kidney transplant recipients is not well established. We, therefore, performed a systematic review of the effects of exercise training in kidney transplantation recipients. We searched two electronic databases for articles up to April 2017. Inclusion criteria were as follows: randomized controlled trial and kidney transplant recipients aged 18 years or older. The main outcomes were allograft function (estimated glomerular filtration rate, eGFR), exercise tolerance (VO2 peak), and quality of life (QOL). After screening of 1303 references in PubMed and Ichushi, six randomized control trials were analyzed. For kidney transplant recipients, supervised exercise training was shown to significantly improve VO2 peak [mean difference 2.42; 95% confidence interval (95%CI) 0.22–4.63] and QOL (mean difference 7.23; 95%CI 0.94–13.52). However, exercise training did not improve allograft kidney function (mean difference 6.22; 95%CI − 13.00 to 25.44). No reporting bias was observed in any of the outcomes. There were no reports including patient survival rates and the harm associated with exercise training. Exercise training for kidney transplant recipients significantly improved exercise tolerability and QOL, but a significant improvement was not obtained with respect to allograft kidney function. Evaluation of patient survival rates and the harm associated with exercise training has not been reported, therefore, future studies are needed to resolve these issues.

AIM Arteriolar hyalinosis (AH) is a common lesion in allograft biopsies taken following kidney transplantation. Recent studies have shown that severe AH may predict transplant outcomes and provide information about previous exposure to certain drugs, such as calcineurin inhibitors (CNI). However, the incidence of AH as a direct result of diabetic nephropathy (DN) after kidney transplantation has not been fully evaluated. This study aimed to assess the impact of primary DN on the development of AH lesions in patients who underwent kidney transplantation. METHODS Eighty-three patients who underwent living-donor kidney transplantation between April 2005 and June 2015 were enrolled in this study. A total of 33 patients had DN prior to transplantation. Allograft biopsies were scored according to the Banff classification, and the relationship between the individual histological lesions and clinical baseline data was assessed. RESULTS At early biopsy (3-12 months), there were no differences in the rates of AH lesions between the DN group and the non-DN group (ah ≥ 1: 37% vs. 41.3%, P = 0.719; aah ≥ 1: 14.8% vs. 6.5%; P = 0.453). However, there were significant differences between the groups in biopsies taken more than 3 years after the transplant (ah ≥ 2: 83.3% vs. 36.8%, P = 0.013; aah ≥ 2: 66.7% vs. 21.1%, P = 0.011). Multivariable analysis showed that both the length of time after transplantation and the presence of DN were independent risk factors for ah ≥ 2 (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.47-19.54, P = 0.011) and aah ≥ 2 (OR: 7.55, 95% CI: 1.49-38.33, P = 0.015). CONCLUSION This is the first report showing that the presence of primary DN disease contributes to the development of severe AH late in the course after kidney allografts.

In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

Several clinical parameters and pathological findings are known to be predictors of the deterioration of diabetic nephropathy (DN). Glomerular basement membrane duplication (GBM-DP) is a pathological feature representing endothelial injury, which is commonly observed in DN. In the present study, we investigated the association between GBM-DP and the renal prognosis in DN. The study enrolled 80 patients with renal biopsy-proven DN who were managed at Chiba-East Hospital from 2005 to 2012. We confirmed the pathological findings according to the Renal Pathology Society classifications, and we further evaluated the GBM-DP, which was defined as double contours of the GBM that expanded more than 10% of capillary loops in the most affected nonsclerotic glomerulus. We used Cox regression models to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), with adjustment for age, sex, systolic blood pressure, HbA1c, estimated glomerular filtration rate (eGFR), and urinary protein excretion (UP) at baseline. Of the 80 patients, 56 were male (70.0%) and the mean age was 59.1 years. The median eGFR and UP were 42 ml/min/1.73 m2 (IQR 30, 59) and 3.1 g/gCr (IQR 1.2, 5.2). Twenty-seven patients progressed to ESRD and one patient died during the median observational period of 2.9 years (IQR 1.5, 4.3). The multivariable analyses showed that GBM-DP was significantly associated with ESRD (HR 3.18 [95% confidence interval (CI): 1.02–9.87], p = 0.045). We newly identified GBM-DP as a strong prognostic predictor in DN patients. Further study is needed to clarify the pathogenic mechanism of GBM-DP in DN.

Arteriolar hyalinosis (AH) is a common lesion in allograft biopsies taken following kidney transplantation. Recent studies have shown that severe AH may predict transplant outcomes and provide information about previous exposure to certain drugs, such as calcineurin inhibitors (CNI). However, the incidence of AH as a direct result of diabetic nephropathy (DN) after kidney transplantation has not been fully evaluated. This study aimed to assess the impact of primary DN on the development of AH lesions in patients who underwent kidney transplantation.Eighty-three patients who underwent living-donor kidney transplantation between April 2005 and June 2015 were enrolled in this study. A total of 33 patients had DN prior to transplantation. Allograft biopsies were scored according to the Banff classification, and the relationship between the individual histological lesions and clinical baseline data was assessed.At early biopsy (3-12 months), there were no differences in the rates of AH lesions between the DN group and the non-DN group (ah ≥ 1: 37% vs. 41.3%, P = 0.719; aah ≥ 1: 14.8% vs. 6.5%; P = 0.453). However, there were significant differences between the groups in biopsies taken more than 3 years after the transplant (ah ≥ 2: 83.3% vs. 36.8%, P = 0.013; aah ≥ 2: 66.7% vs. 21.1%, P = 0.011). Multivariable analysis showed that both the length of time after transplantation and the presence of DN were independent risk factors for ah ≥ 2 (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.47-19.54, P = 0.011) and aah ≥ 2 (OR: 7.55, 95% CI: 1.49-38.33, P = 0.015).This is the first report showing that the presence of primary DN disease contributes to the development of severe AH late in the course after kidney allografts.

Objective To examine the association between degree of underreporting energy intake and psychosocial (including interpersonal and personal) factors among hemodialysis patients in Japan. Design We conducted a cross-sectional study. Predictors of difference were identified using multiple linear regression analysis. Setting Study was conducted at a public hospital and a dialysis clinic in a single district in northeast Honshu, Japan. Subjects Participants were hemodialysis outpatients. Patients aged more than 20 years and undergoing treatment for end-stage renal disease for at least 6 months were included. Exclusion criteria were diagnosis of depression, a mental disease, or dementia. Main Outcome The outcome measure was the difference in reported energy intake defined by the differences between a brief administered dietary history questionnaire and diet record stratified by standardized weight. Results Seventy patients undergoing hemodialysis participated (44 men [62.9%] and 26 women [37.1%]). Of these, 54.3% underreported energy intake (by >10%). Sex (male) and employment status (employed) were statistically associated with energy intake underreporting. A lower score of dialysis staff encouragement was associated with greater energy intake underreporting (β coefficient=3.89 kcal/standardized weight, 95% confidence interval: 0.89 to 6.90; P = .012). Conclusion Degree of underreporting energy intake is significantly associated with interpersonal psychosocial factors among hemodialysis patients in Japan. The interpersonal relationship with encouragement by the dialysis staff is important in improving the accuracy of reporting energy intake among dialysis patients.

Calcineurin inhibitors (CNI) have been commonly used as pivotal immunosuppressive agents to renal transplant recipients and have contributed significantly to improving short-term allograft survival. However, long-term administration of CNI may cause an adverse effect on kidney function, known as chronic nephrotoxicity. Chronic CNI nephrotoxicity (CNI-NT) shows characteristic histopathological findings that involve arteriolar hyalinosis. Recently, the term alternative arteriolar hyalinosis (aah) is used to discriminate CNI-specific arteriolar hyaline deposition from non-specific arteriolar hyalinosis. We studied whether arteriolar vacuolization represents an early lesion of aah as a predictor of CNI-NT. We retrospectively studied the 79 patients under treatment with a CNI immunosuppressant, who underwent living-related renal transplantation (RTx) from January 2007 to March 2009. We examined serial protocol graft biopsies at one h, one, six, and 12 months after RTx. We classified histological findings into two groups on the basis of aah lesion (with or without aah) in serial biopsies for 12 months. Arteriolar vacuolization was more frequently observed in the aah group than in the non-aah group with a significant difference. Arteriolar vacuolization was found even in the one-h biopsy specimens, indicating a non-specific histopathological finding. But in the aah group, arteriolar vacuolization tended to be more frequently observed later on. Aah can be a predictor of CNI-NT.

Objectives: Cerebrospinal fluid (CSF) lactate is produced by bacterial anaerobic metabolism and is not affected by blood lactate concentration, an advantage over CSF glucose in differentiating bacterial meningitis from aseptic meningitis. However, the previous investi- gations have shown mixed results of the sensitivity and specificity. Our study’s purpose was to assess the utility of CSF lactate in differentiating bacterial meningitis from aseptic meningitis. Methods: We searched MEDLINE and EMBASE for clinical studies that included CSF lactate mea- surement in bacterial meningitis and aseptic meningitis. Test characteristics were pooled using hierarchical summary ROC curve and random effects model. Results: Thirty three studies were included. The pooled test characteristics of CSF lactate were sensitivity 0.93 (95% CI: 0.89 e 0.96), specificity 0.96 (95% CI: 0.93 e 0.98), likelihood ratio positive 22.9 (95% CI: 12.6 e 41.9), likelihood ratio negative 0.07 (95% CI: 0.05 e 0.12), and diag- nostic odds ratio 313 (95% CI: 141 e 698). Pretreatment with antibiotics lowered the sensitivity 0.49 (95% CI: 0.23 e 0.75). CSF lactate of around 35 mg/dl (34 e 36 mg/dl) had higher sensitivity and specificity than those of around 27 mg/dl (26 e 28 mg/dl). Conclusions: CSFlactate’s highnegative likelihoodratio may make it useful for rulingoutbacterial meningitis though pretreatment with antibiotics reduces clinical accuracy. CSF lactate of 35 mg/dl could be optimal cut-off value for distinguishing bacterial meningitis from aseptic meningitis.

Background: We examined associations of C-reactive protein (CRP) levels with mortality in Japanese hemodialysis patients and trends in prevalence of CRP measurement at hemodialysis facilities internationally. To assess whether measurement of CRP may influence outcomes, we examined associations of facility prevalence of CRP measurement with mortality. Methods: CRP measurements were from a cross-section of patients in the international Dialysis Outcomes and Practice Patterns Study (n = 610 facilities, 16,355 patients). Cox proportional hazards models assessed associations of mortality with CRP in Japan, and with a facility’s frequency of measuring CRP internationally, (except in the USA and Canada). Results: From 2002–2004, CRP was measured in 0–19% of patients in each country, except Japan (55%). From 2005–2007, CRP was measured in ≧50% of country patients except in Canada (15%) and the USA (2%). After multivariable adjustment, the hazard ratio (HR) of death was 1.6- to 2.4-fold higher (p < 0.05) for various categories of CRP levels >3 mg/l (vs. Conclusions: CRP is informative regarding mortality risk beyond that provided by other inflammatory and nutritional markers, with significantly higher risk seen at CRP >3 mg/l. Greater use of CRP may lead to improved patient care as suggested by the association of greater CRP measurement with lower cardiovascular mortality.

Recurrence of glomerulonephritis (GN) is one of the major risk factors of long-surviving renal graft dysfunction. Cryoglobulinemic glomerulonephritis of hepatitis-C virus (HCV)-negative patient is a rare cause of end-stage renal disease. There is little case report of recurrent cryoglobulinemic glomerulonephritis in negative HCV recipients after renal transplantation. We represent a renal allograft recipient of an interesting recurrent cryoglobulinemic glomerulonephritis. The patient was diagnosed with mixed cryoglobulinemic glomerulonephritis by kidney biopsy at the age of 32 . He had no HCV, HBV nor liver dysfunction. He received immunosuppressive therapy, however, was introduced to hemodialysis treatment after 13 yr. He received a cadaveric renal transplantation at the age of 50, and immunosuppressive treatment was started with ciclosporin, prednisolone and mycophenolate mofetil (MMF). Four yr after transplantation, he developed fever and purpura of lower limbs. His serum creatinine level did not increase, however, proteinuria, hematuria, hypocomplementemia, positive rheumatoid factor and mixed cryoglobulinemia were noted. Detailed analysis failed to reveal the composition of mixed cryoglobulinemia. The renal allograft biopsy showed membranoproliferative-type GN with monocyte and polynuclear leukocyte accumulation of capillary loops and small cellular crescent. Immunofluorescent study showed C3, IgG and IgM deposition of mesangial and capillary pattern. Regardless of steroid pulse therapy, hypocomplementemia and positive rheumatoid factor did not improve. Ten yr after transplantation, he was affected by cellulitis and sepsis. Afterward, rising of serum creatinine and nephrotic range proteinuria developed. The allograft biopsy revealed advanced cryoglobulinemic glomerulonephritis with characteristic vascular lesions. Electron microscopy showed organized subendothelial deposits compatible with cryoglobulinemic glomerulonephritis and proteinaceous thrombus in arteriole.

Background: Considerable controversy existsover the impact of the biocompatibility and flux characteristics ofdialyzer membranes on anemia in chronic hemodialysis patients. Methods: A subset of 1,207 subjects from the Japanese arm of DOPPS phase II was analyzed. Results: Patient characteristics included mean age 59 years, male sex 60%, BMI 20.6, time on dialysis therapy 7.8 years, and diabetes rate 27%. Dialysis parameters were Kt/V 1.33, and normalized protein catabolic rate 1.05 g/kg/day. Initial hemoglobin level was 10.1 g/dl. 79% were treated by intravenous erythropoietin with mean weekly doses of 4,500 IU. Hemoglobin levels and erythropoietin doses during 2-year study period were not affected by dialysis membrane biocompatibility (unmodified cellulose or biocompatible) or flux (standard or high performance). The 2-year survival rate was 90.9% and was influenced by older age, presence of cardiovascular diseases and amyloidosis, lower levels of BMI and serum albumin, but not by other variables, including dialysis membranes. Use of biocompatible membranes was associated with a lower all-cause mortality (8.3 vs. 13.0% for bioincompatible, p = 0.037), but this difference was not significant in multivariate analyses (hazard ratio 0.70, p = 0.17 by Cox multivariate analysis). Conclusion: The biocompatibility and permeability of dialyzer membranes had no effect on anemia, erythropoietin dosage or all-cause mortality in Japanese chronic hemodialysis patients treated by non-reuse dialysis.

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.

It is unknown whether regular patient-doctor contact (PDC) contributes to better outcomes for patients undergoing hemodialysis. Here, we analyzed the associations between frequency and duration of PDC during hemodialysis treatments with clinical outcomes among 24,498 patients from 778 facilities in the international Dialysis Outcomes and Practice Patterns Study (DOPPS). The typical facility PDC frequency, estimated by facility personnel, was high (more than once per week) for 55% of facilities, intermediate (once per week) for 24%, and low (less than once per week) for 21%. The mean ± SD estimated duration of a typical interaction between patient and physician was 7.7 ± 5.6 minutes. PDC frequency and duration varied across DOPPS phases and countries; the proportion of facilities with high PDC frequency was 17% in the United States and 73% across the other countries. Compared with high PDC frequency, the adjusted hazard ratio (HR) for all-cause mortality was 1.06 (95% confidence interval [CI], 0.96 to 1.17) for intermediate PDC frequency and 1.11 (95% CI, 1.01 to 1.23) for low PDC frequency (P=0.03 for trend). Furthermore, each 5-minutes-shorter duration of PDC was associated with a 5% higher risk for death, on average (HR, 1.05; 95% CI, 1.01 to 1.09), adjusted for PDC frequency and other covariates. Multivariable analyses also suggested modest inverse associations between both PDC frequency and duration with hospitalization but not with kidney transplantation. Taken together, these results suggest that policies supporting more frequent and longer duration of PDC may improve patient outcomes in hemodialysis.

We herein describe the case of a 40-year-old Japanese male who was admitted to our hospital because of a continuous remittent fever lasting 1 month. He fulfilled the items of the classification criteria for the diagnosis of systemic lupus erythematosus (SLE). The administration of 20 mg per day of oral prednisolone completely diminished his clinical symptoms. However, his renal biopsy performed 1 day after the admission showed marked pathognomonic characteristics. Not only did his glomeruli show class I lupus nephritis with mesangial depositions of IgG, IgA, C3, and C1q, but also tubulointerstitial nephritis with marked T-lymphocyte infiltration. These infiltrated T cells partly had nuclear atypia. The patient was positive for human T cell leukemia virus type 1 (HTLV-1) antibodies. Furthermore, clonal rearrangements of T cell receptor-gamma chain gene was detected in the DNA extracted from his kidney sections by the polymerase chain reaction (PCR) method. A second renal biopsy 6 months after the prednisolone treatment showed that the infiltrating T lymphocytes had markedly diminished. This is the first case report of lupus nephritis class I with tubulointerstitial nephritis, which might include oncogenic T lymphocytes, in an HTLV-1 positive patient.

Background The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number. Methods/Design The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice. Discussion This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice. Trial registration UMIN-Clinical Trial Registration, UMIN000004784.

Acute glomerulonephritis (AGN) is one of the most common renal diseases. They are often associated with infections and can result in diffuse proliferative glomerulonephritis (GN). This case report reviews an interesting case in which renal endarteritis coexisted in AGN with diffuse endocapillary proliferation. The discussion highlights important pathological findings and clinical aspects in acute endocapillary proliferative GN with renal endarteritis. Coexisting endarteritis should be in the differential diagnosis of AGN in patients with persistent clinical courses.

Calcineurin inhibitors (CNI) have been commonly used as pivotal immunosuppressive agents to renal transplant recipients and have contributed significantly to improving short-term allograft survival. However, long-term administration of CNI may cause an adverse effect on kidney function, known as chronic nephrotoxicity. Chronic CNI nephrotoxicity (CNI-NT) shows characteristic histopathological findings that involve arteriolar hyalinosis. Recently, the term alternative arteriolar hyalinosis (aah) is used to discriminate CNI-specific arteriolar hyaline deposition from non-specific arteriolar hyalinosis. We studied whether arteriolar vacuolization represents an early lesion of aah as a predictor of CNI-NT. We retrospectively studied the 79 patients under treatment with a CNI immunosuppressant, who underwent living-related renal transplantation (RTx) from January 2007 to March 2009. We examined serial protocol graft biopsies at one h, one, six, and 12 months after RTx. We classified histological findings into two groups on the basis of aah lesion (with or without aah) in serial biopsies for 12 months. Arteriolar vacuolization was more frequently observed in the aah group than in the non-aah group with a significant difference. Arteriolar vacuolization was found even in the one-h biopsy specimens, indicating a non-specific histopathological finding. But in the aah group, arteriolar vacuolization tended to be more frequently observed later on. Aah can be a predictor of CNI-NT.