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Background In Japan, forgoing life-sustaining treatment to respect the will of patients at the terminal stage is not stipulated by law. According to the Guidelines for the Decision-Making Process in Terminal-Stage Healthcare published by the Ministry of Health, Labor and Welfare in 2007, the Japanese Society for Dialysis Therapy (JSDT) developed a proposal that was limited to patients at the terminal stage and did not explicitly cover patients with dementia. This proposal for the shared decision-making process regarding the initiation and continuation of maintenance hemodialysis was published in 2014. Methods and results In response to changes in social conditions, the JSDT revised the proposal in 2020 to provide guidance for the process by which the healthcare team can provide the best healthcare management and care with respect to the patient's will through advance care planning and shared decision making. For all patients with end-stage kidney disease, including those at the nonterminal stage and those with dementia, the decision-making process includes conservative kidney management. Conclusions The proposal is based on consensus rather than evidence-based clinical practice guidelines. The healthcare team is therefore not guaranteed to be legally exempt if the patient dies after the policies in the proposal are implemented and must respond appropriately at the discretion of each institution.

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs.

Background There are no reports of a large-scale survey on the infection prevention measures against coronavirus disease 2019 (COVID-19) in nephrology facilities. This study investigated the facility-level nephrology practices adopted during the COVID-19 pandemic and their associated challenges. Additionally, the treatment patterns and outcomes of chronic kidney disease (CKD) patients with COVID-19 were reviewed. Methods We conducted a nationwide questionnaire survey of 704 educational facilities that were certified by the Japanese Society of Nephrology (JSN) from October 20, 2020 to November 16, 2020. The questionnaire reviewed the facility characteristics, infection prevention measures taken during routine nephrology practice, impact of COVID-19 on nephrology practice, experiences in managing CKD patients with COVID-19, and nosocomial transmission in the nephrology unit. Results Of the 347 facilities that responded, 95.1% checked outpatients’ body temperatures and COVID-19 symptoms at their visits. To reduce face-to-face contact, 80% and 70% of the facilities lengthened the intervals between outpatient visits and introduced online/telephonic consultations, respectively. As a result, more than half of the hospitals experienced a decrease in the numbers of outpatients and inpatients (64% and 50%, respectively). During the study period, 347 facilities managed 479 CKD patients with COVID-19. Oxygen administration and mechanical ventilation were performed for 47.8% and 16.5% of the patients, respectively, with a 9.2% total mortality rate. Conclusion This survey demonstrated that JSN-certified educational nephrology facilities adopted multiple measures to manage the COVID-19 pandemic; however, they faced several challenges. Sharing these experiences could standardize these approaches and prepare us better for the future. Supplementary Information The online version contains supplementary material available at 10.1007/s10157-021-02082-z.

Background Major symptoms of progressive chronic kidney disease (CKD) are similar to those of hypothyroidism. Hidden symptoms of hypothyroidism underlying CKD are often observed in clinical practice. This study aimed to ascertain the frequency of hypothyroidism complicated by CKD, and to analyze factors impacting thyroid function. Methods During the period from April 2012 through October 2016, 510 CKD patients at our outpatient clinic were measured thyroid and kidney function for diagnosing hypothyroidism (overt hypothyroidism, OH; subclinical hypothyroidism, SH; non-thyroidal illness, NTI) and evaluating the stage of CKD. All patients were over 15 years of age. Results There were significant differences in age, estimated glomerular filtration rate (eGFR), urinary protein (UP), and serum albumin (Alb) among patients with OH, SH, and NTI compared to the normal group in univariate and multivariate analyses. UP showed the highest odds ratio of OH, SH, and NTI but no differences were recognized in gender in each group. Frequency distribution showed that the prevalence of thyroid dysfunction was greater among more severe stage of CKD with higher amount of UP. OH and SH did not show high positive ratio of anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). NTI and normal subjects showed higher positive ratio as 50.0% and 42.9% of TgAb and TPOAb than OH and SH. Conclusions Hypothyroidism complicated by CKD exhibited a high prevalence. Age, eGFR, UP, and serum Alb were related to the prevalence of hypothyroidism, whereas gender was not and this was contradicted to the prevalence of hypothyroidism in general population. The prevalence of OH and SH was higher among patients with higher stage of CKD with increased UP. Hypothyroidism complicated by CKD may involve different onset mechanisms unrelated to antithyroid antibodies (ATAb). In CKD patients, assessments of OH and SH, as well as NTI, are needed for proper diagnosis.

Aim: Medullary ray injury was recently reported in renal transplant biopsies. This study was performed to clarify the clinicopathological features of medullary ray injury in paediatric living renal transplant recipients. Methods: Paediatric recipients who completed a 5-year follow-up after living renal transplantation were enroled. We evaluated the clinical and pathological parameters of the presence or absence of medullary ray injury in their 1-year protocol biopsies. Results: Of 48 1-year protocol biopsies, 18 (37.5%) showed histological evidence of medullary ray injury. The 48 paediatric recipients were classified as those with medullary ray injury (n = 18; MRI-1Y [+] group) and those without medullary ray injury (n = 30; MRI-1Y [−] group) in the 1-year protocol biopsies. The prevalence of histological evidence of calcineurin inhibitor (CNI) nephrotoxicity, chronic obstruction or reflux nephropathy, and imaging findings of vesicoureteral reflux was 66.7, 22.2, and 7.7% in the MRI-1Y (+) group and 33.3, 13.3, and 15.4% in the MRI-1Y (−) group, respectively. Only the prevalence of CNI nephrotoxicity was significantly different between the 2 groups. There was no significant difference in the mean estimated glomerular filtration rate at 1, 3, or 5 years after transplantation between the 2 groups. Conclusion: In total, 37.5% of 1-year protocol biopsies showed histological evidence of medullary ray injury. This finding suggests that CNI nephrotoxicity might be the main contributor to medullary ray injury in 1-year protocol biopsies. The presence of medullary ray injury had little influence on renal function, at least during the first 5 years after transplantation.

Aim: This study evaluated the clinicopathological findings of acute/active antibody-mediated rejection (AABMR) according to the Banff 2013 classification. Methods: We analyzed 345 biopsies of 269 kidney transplant recipients. Pathological AABMR (PAABMR) was defined as histological evidence of acute tissue injury and endothelial injury by light microscopy regardless of donor-specific antibodies (DSAs). Results: Among the 345 biopsies, 29 (8.4%) were diagnosed as PAABMR. The mean g score was 1.17 ± 0.60, the mean ptc score was 1.97 ± 1.32, and DSA positivity was found in 69% of PAABMR. The mean duration after transplantation was 22.9 ± 26.7 months. Among 3 groups (DSA-high, mean fluorescence intensity (MFI) ≥ 5,000; DSA-low, MFI < 5,000 to ≥1,000; below cutoff), ABO incompatibility in DSA-high was significantly lower and second transplantation in DSA-high was significantly higher. We found 83% of PAABMR by the protocol biopsy (subclinical AABMR [SAABMR]). The short-term clinical and light microscopical changes in 8 cases of SAABMR did not show worsening during follow-up period (9–24 months). However, ultrastructural finding, including glomerular endothelial swelling, subendothelial electron-lucent widening, and early glomerular basement duplication, were found by electron microscopy (EM) in the first biopsies, and half of the SAABMR cases developed de novo circular peritubular capillary multilayering in the follow-up biopsies. Conclusion: PAABMR was mainly found by the protocol biopsy. The short-term follow-up of SAABMR patients did not show worsening clinically and light microscopically, but ultrastructural examination by EM was useful to detect early lesions of endothelial injury and progression of glomerular and peritubular capillary basement membrane alterations.

Background Malignancy after kidney transplantation (KT) is one of the most serious post-transplant complications. This study aimed to investigate the incidence, type, and outcomes of malignancy after pediatric KT. Methods We performed a retrospective cohort study on pediatric kidney transplant recipients aged 18 years or younger who received their first transplant between 1975 and 2009. Results Among the 375 children who underwent KT, 212 were male (56.5%) and 163 were female (43.5%) (median age at KT, 9.6 years [interquartile range {IQR}] 5.8–12.9 years). The incidence of malignancy was 5.6% (n = 21). The cumulative incidences of cancer were 0.8%, 2.5%, 2.8%, 4.2%, 5.5%, and 15.6% at 1, 5, 10, 15, 20, and 30 years post-transplantation, respectively. Of 375 patients, 12 (3.2%) had solid cancer and nine (2.4%) had lymphoproliferative malignancy. The median age at the first malignancy was 21.3 years (IQR 11.5–33.3 years). The median times from transplant to diagnosis were 22.3 years (IQR 12.3–26.6 years) for solid cancer and 2.2 years (IQR 0.6–2.8) for lymphoproliferative malignancies. During follow-up, five recipients died due to malignancy. The causes of death were hepatocellular carcinoma in one patient, squamous cell carcinoma in the transplanted kidney in one patient, malignant schwannoma in one patient, and Epstein-Barr virus-related lymphoma in two patients. The mortality rate was 0.79 per 1000 person-years (95% confidence interval 0.38, 1.85). Conclusions Early diagnosis and treatment of malignancies in transplant recipients is an important challenge. Therefore, enhanced surveillance and continued vigilance for malignancy following KT are necessary.

Because of the severe shortage of suitable deceased donors, ABO-incompatible living donor kidney transplantation (ABOi LDKT) is performed even in pediatric recipients in Japan. We performed pediatric ABOi LDKT using rituximab without anti-A/B antibody removal. Thirteen pediatric recipients (mean age 7.4, range 3.4–15.7, four females) whose baseline anti-A/B IgG titers were ≤ × 64 underwent ABOi LDKT without antibody removal and splenectomy between July 2013 and April 2017 at Toho University. Mycophenolate mofetil (MMF) was initiated on day − 10. Rituximab (100 mg) was administered twice. Basiliximab and triple maintenance immunosuppression (calcineurin inhibitor, MMF, and steroids) were administered. Protocol biopsy was performed at 3 months and 1 year after transplantation. We retrospectively compared the clinical outcomes between these recipients and 37 children (mean age 9.0, range 2.6–18.9, 15 female) who underwent ABO-compatible (ABOc) LDKT during the same period. The mean follow-up periods of ABOi and ABOc groups were 31.9 ± 13.5 and 28.8 ± 14.4 months, respectively. In the ABOi group, no clinical acute rejection (AR) was noted and subclinical AR was observed in four patients without evidence of acute antibody-mediated rejection. In the ABOc group, clinical and subclinical AR developed in 3 and 10 patients, respectively. No significant difference was identified for the mean eGFR between the ABOi and ABOc groups (98.3 ± 48.8 vs. 86.9 ± 39.4, P = 0.452 at 3 months; 78.2 ± 21.2 vs. 79.7 ± 21.3, at 1 year, P = 0.830). Death-censored graft survival at follow-up was 100% in the ABOi group and 94.6% in the ABOc group. Patient survival during the follow-up period in both the groups was 100%. Late-onset neutropenia (LON) requiring granulocyte colony-stimulating factor occurred more frequently in the ABOi group than in the ABOc group (4 vs. 0 patients) (P

Background Lipofuscin is an indicator of aging. We examined the clinicopathologic significance of lipofuscin deposition in the renal tubules of renal allografts. Method We analyzed allograft biopsy specimens from living kidney transplantations from January to December 2015. For controls, we analyzed native kidney biopsy specimens obtained from January 2015 to December 2016. We identified granules with a yellow-to-tan shade in renal tubules as lipofuscin. Results The donor age at transplantation was significantly older in lipofuscin deposition biopsy specimens than in those without, whereas the time after transplantation age was not different between the 2 groups with renal allografts. In native kidney biopsies, age at biopsy was significantly older in lipofuscin deposition biopsy specimens than in those without. We compared “massive lipofuscin deposition,” defined as lipofuscin deposition on both sides of 3 or more renal tubules, and donor-age matched control allograft biopsies without lipofuscin deposition. Comparing these 2 groups, recipient age at transplantation was significantly older in the massive lipofuscin deposition group. Conclusion Lipofuscin deposition on tubular epithelium is not a surrogate marker of aging of kidneys allografts, although lipofuscin deposition was significantly greater in older tissues from native kidneys. The older age of recipients may be associated with massive lipofuscin deposition in renal allografts.

OBJECTIVES Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients. MATERIALS AND METHODS Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups. RESULTS In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function. CONCLUSIONS Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.

Background/Aims: To examine the relationship of extracellular fluid (ECF) volume and osmotic excess with treatment modality, we retrospectively analyzed spontaneous body weight loss and osmotic excretion versus true body weight after kidney transplantation in peritoneal dialysis (PD) patients and preemptive transplant recipients compared with hemodialysis (HD) patients. We also examined maximum bladder volume in other transplant recipients on PD. Methods: From 2005 to 2011, 42 PD patients underwent kidney transplantation at our institution. Patients aged 2 at transplantation). From 2005 to 2006, 29 adult living-related donor kidney transplant recipients on HD support (HD group) were enrolled as controls (age 36.4 ± 11.3 years; dialysis duration 37.5 ± 55.2 months). Results: Percentage body weight loss at 1 month after transplantation was 5% from ideal body weight for the PD group (51.2 ± 14.3 to 48.6 ± 13.0 kg, p = 0.002), 5.1% for the preemptive group (56.7 ± 17.4 to 53.8 ± 16.5 kg, p = 0.0005), and 1% for the HD group (52.9 ± 12.4 to 52.1 ± 12.5 kg, p = 0.079); post-transplantation 24-h osmotic excretion was greater in the PD and preemptive groups (387.3 ± 175.7 mOsm) groups than in HD (250 ± 124 mOsm; p = 0.006. Another 69 adult living-related donor kidney transplant recipients (PD and HD support) with dialysis duration ≤5 years were examined. Mean dialysis duration differed in the HD (17.5 ± 13.1 months) and PD (29.6 ± 20.4 months, p = 0.015) groups; mean urine volume and maximum desire to void (MDV) were similar. Conclusion: ECF volume and osmotic excess occurred in the PD and preemptive groups compared with the HD group pre-transplantation. Although PD maintains MDV and residual and total urine volume, ECF volume and osmotic excess should be monitored before transplant; pre-transplant HD support should always be considered in PD and preemptive transplant patients.

Background Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients. Methods Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient’s self-report during the one-year period. Results Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22–4.52], P Conclusions Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.

Aim: Low-vacuum scanning electron microscopy (LVSEM) has been reported to aid in diagnosis of renal biopsy. This study evaluated early transplant glomerulopathy in kidney transplant recipients using LVSEM. Methods: We selected 4 biopsies of cg0, 5 biopsies of cg1a, 5 biopsies of cg1b, and 4 biopsies of cg2 lesions that had been evaluated by light microscopy (LM) and transmission electron microscopy from recipients with acute/active or chronic, active antibody-mediated rejection (AABMR or CAABMR). Renal allograft paraffin sections (1 µm thickness) were stained with periodic acid-methenamine silver and observed using LVSEM. The cg score was based on the Banff classification. The parameter “percentage of duplicated capillary number” was calculated as follows: in 1 glomerulus with glomerular basement membrane (GBM) duplication, the total duplicated capillary number/the total number of capillaries ×100. Results: In all 4 biopsy specimens with AABMR showing cg0, LVSEM revealed GBM duplication not identified by LM. The average percentage of duplicated capillary number per glomerulus with GBM duplication was higher when observed by LVSEM than when observed by LM in all cg1b and cg2 biopsy specimens. Conclusion: LVSEM revealed early GBM duplication in AABMR. Early GBM duplication might progress in the very early phase of AABMR. GBM duplication was more frequently detected by LVSEM than by LM in biopsy specimens with early chronic, active antibody mediated rejection. Thus, LVSEM may be useful in diagnosis of early transplant glomerulopathy.

Despite the advances in management, acute decompensated heart failure (ADHF) continues to be associated with poor clinical outcomes. Renal dysfunction, especially acute kidney injury (AKI), is one of the strongest predictors of adverse outcomes in ADHF. The association between the heart and the kidney in patients with ADHF is complex, and a complete understanding of this bidirectional interaction has not been elucidated. There are two big issues in this field. First is that many different definitions for renal dysfunction have been used conventionally. This would create different interpretations of renal failure in ADHF. Another problem is that the timing of WRF/AKI onset during hospitalization varies. To reconsider the future direction of AKI, this review focused on the current perspectives on AKI in ADHF patients.

To determine the impact that end-stage kidney disease (ESKD) has on ocular microcirculation in the optic nerve head (ONH) and choroid area shown by laser speckle flowgraphy (LSFG). We studied 24 consecutive Japanese patients with ESKD who visited the department of Nephrology at our hospital and 55 age- and gender-matched subjects who had undergone polysomnography. The mean blur rates (MBRs) in vessels (MBR-Vessel), in the tissue (MBR-Tissue), throughout the ONH (MBR-All), and throughout the choroid (MBR-Choroid) were analyzed. We divided the MBR-Tissue into four sections (superior, temporal, inferior, and nasal). The results of systemic and ocular parameters were compared between the ESKD patients and control subjects. We performed single and multiple regression analyses to determine the MBR section(s) that correlated most strongly with serum creatinine and the estimated glomerular filtration rate (eGFR) and to identify the independent factors for selected MBR sections in the ESKD patients. All sections of the ONH in the ESKD patients were significantly lower than those in the control subjects. MBR-Choroid was not significantly different between the control and ESKD groups. The single regression analyses revealed that MBR-Tissue had the strongest correlations with creatinine and the eGFR. The multiple regression analyses revealed hematocrit, creatinine, and eGFR as factors independently contributing to the MBR-Tissue. The inferior section of MBR-Tissue was most strongly correlated with creatinine and the eGFR. The MBRs in the ONH of the ESKD patients decrease compared with control subjects and the inferior section of MBR-Tissue is correlated with serum creatinine and eGFR.

A 35-year-old woman with membranoproliferative glomerulonephritis type I had quintuplet gestation after induced ovulation. Her serum creatinine level and estimated glomerular filtration rate were 0.86 mg/dL and 61.5 mL/min/1.73 m2 before pregnancy. Blood pressure was normal and urinary protein to creatinine ratio was 0.2 g/gCr. Prednisolone 10 mg on alternate-day administration was continued during pregnancy. At 10 weeks of gestation transvaginal selective embryo reduction was performed and five embryos were reduced to twins. Hypertension occurred at 20 weeks of gestation. She developed nephrotic syndrome and serum creatinine level increased to 1.29 mg/dL. Elective cesarean section was performed at 28 weeks of gestation and dichorionic diamniotic twins were born. After delivery blood pressure, serum creatinine level, estimated glomerular filtration rate and serum albumin level in their mother returned to baseline. Her twin infants were well at discharge from neonatal-intensive-care-unit. Incidence of multifetal pregnancies due to the improvement of assisted reproduction technologies and ovulation-inducing hormones has been increasing. Management for multifetal pregnancy in women with chronic kidney disease will be needed further.

Background The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. Conclusions In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

Background We investigated whether serum uric acid (SUA) levels before kidney transplantation predict new-onset diabetes after kidney transplantation (NODAT) and compared SUA levels with known risk factors for NODAT by prospective cohort study. Methods A total of 151 adult kidney recipients without diabetes (84 men, 67 women) who underwent living-donor kidney transplantation between 2001 and 2011 were followed in this study. The Cox proportional hazards model was used to analyse the risk of NODAT. Results During the follow-up period (median 3.3 years, range 0–10 years), 32 (21.2%) adult kidney recipients without diabetes developed NODAT, and an incidence rate was 5.6 per 100 person-years and a 10-year cumulative incidence of 26.9%. When subjects were stratified by SUA levels into tertiles, the patients in the highest tertile (> 8.6 mg/dl for men, > 7.7 mg/dl for women) had a significantly higher risk of NODAT than the patients in the lower 2 tertiles (log-rank test, P = 0.03). In the univariate analysis, increased level of SUA was associated with NODAT (hazard ratio 1.27 [95% CI 1.04–1.55], P = 0.01). In the multivariate analysis, increased level of SUA was significantly associated with NODAT after correction by any factors, e.g. (age, sex, family history of diabetes, BMI, HbA1c, serum creatinine, tacrolimus, HCV) factors directly affecting the SUA value (1.26 [1.02–1.56], P = 0.03), risk factors for T2DM onset (1.34 [1.10–1.64], P = 0.03), and factors previously reported risk factors for NODAT (1.36 [1.11–1.66], P = 0.003). Conclusion SUA independently predicts NODAT in living-donor kidney transplantation patients.

AIM The present study was performed to examine the clinicopathological significance of hyaline deposits in the smooth muscle of the interlobular artery (interlobular hyaline arteriopathy [IHA]) in renal allografts. METHODS Tissue specimens that included the interlobular artery from biopsies performed from January 2012 to December 2015, as well as specimens from biopsies performed ≥1 year after living kidney transplantation were analyzed. Biopsies of recipients with new-onset diabetes mellitus after transplantation were excluded, as well as those of recipients who had undergone transplantation because of diabetic nephropathy. Arteriolopathy was evaluated using the aah score determined by the Banff 2007 classification. RESULTS In total, 51 specimens with IHA lesions were identified among 381 biopsies obtained from 243 recipients performed ≥1 year after kidney transplantation. Among these 51 biopsies, 18 specimens had a score of aah3, 29 had a score of aah2, and four had a score of aah1. The incidence of IHA lesions was 3.6% at ≥1 to

Accurate interpretation of renal allograft biopsy is necessary to guide therapy, especially when an episode biopsy is taken to rescue the graft. Contrarily, a protocol biopsy is carried out routinely to identify baseline conditions (biopsy at 0 or 1 h), subclinical rejection, histological change under current immunosuppression regimen, drug nephrotoxicity, viral infection, and recurrence of glomerulonephritis. Semiquantitative scoring for active lesions including tubulitis, glomerulitis, capillaritis, arteritis, arteriopathy, and others such as polyomavirus infection are key factors in transplant pathology. Recently, the Banff classification has proposed several novel concepts focused on antibody-mediated rejection (ABMR). This review presents the interpretation of transplant pathology from rejection to infection, recurrence of glomerulonephritis, and drug nephrotoxicity, with a description of ABMR according to the 2013 and 2017 Banff classification.

Fluid volume overload is common and is associated with adverse outcomes in hemodialysis patients. Practicing physicians individually manage fluid volume balance in their dialysis patients according to blood pressure, interdialytic weight gain, cardiac function, nutritional status, and other comorbidities. However, accurate assessment of fluid volume status remains a concern. Indicators of dry weight target have been explored further with newer concepts and technologies. In general, total body water comprises approximately 50%-60% of adult body weight (range, 45%-75%), and water comprises 73.3% of lean body mass. The standard hydration status between intracellular water and extracellular water is maintained at a ratio of 62:38 in healthy adults, which, however, is influenced universally by body cell volume driven by age and muscle mass. Fluid volume imbalance in dialysis patients also is characterized primarily by decreased body cell mass associated with aging and muscle attenuation, as well as excess extracellular water content associated with sodium retention, which may be associated with the reserve capacity for volume overload. Indeed, dialysis patients with a leaner body mass have a higher prevalence of hypertension, poorer hypertension control, and greater left ventricular hypertrophy. Understanding of these body composition changes by aging and sarcopenia can aid clinical decision making in the dry weight assessments in dialysis patients. Advising patients with consistently high interdialytic weight gain to practice salt restriction and providing appropriate nutritional support for malnourished patients with downward trajectory in their dry weight would be of great help to achieve optimal fluid volume status.

Summary Introduction Kidney transplantation (KTx) is the most effective treatment for end-stage renal disease in children. Objectives We aimed to compare the long-term outcomes and surgical complications of the intraperitoneal approach (IPA) and extraperitoneal approach (EPA) for KTx in children weighing Study design We performed a retrospective cohort study on pediatric kidney transplant recipients, weighing Results The median follow-up duration was 14.1 years (interquartile range, 9.0–19.2). Comparing the two groups (IPA group, n = 62; EPA group, n = 38), the median age and body weight were significantly lower in the IPA group (4.2 vs. 4.8 years, P = 0.03; 11.7 vs. 13.0 kg, P Discussion We assessed the long-term outcomes of the surgical approaches used for pediatric patients weighing Conclusion The transplant approach did not influence the long-term outcomes in children weighing Summary Table . Comparison of surgical complications by surgical approach. Variables IPA group (n = 62) EPA group (n = 38) P-value Early surgical complications 15 (24%) 1 (3%) Urinary leak 3 0 Urinary stenosis 1 0 Ileus 2 0 Renal artery thrombosis 1 0 Renal vein thrombosis 1 0 Anastomotic bleeding 1 0 Lymphocele 1 0 Wound infection 1 0 Renal allograft compression syndrome 4 1 Late surgical complications 9 (15%) 1 (3%) 0.08 Ileus 6 0 Bowel obstruction 2 0 Urinary stenosis 0 1 Bladder stone (due to sutures) 1 0 Total 24 (39%) 2 (6%) Surgical reintervention 10 (16%) 1 (3%) 0.05 EPA, extraperitoneal approach; IPA, intraperitoneal approach; KTx, kidney transplantation. Values are presented as numbers (%). Early surgical complications were identified within 30 days post-KTx. Late surgical complications were defined as complications occurring more than 1 month post-KTx.

Despite restoration of fertility after kidney transplantation, the benefit is limited in female kidney recipients. Our objective is to determine the reasons for this discrepancy.We evaluated 315 women who underwent kidney transplantation from 1983 to 2015 (a median of age at transplantation [10th-90th percentile] of 32 years [7-55 years]); 230 recipients between the ages of 15 to 49 years old as of March 2016 were observed.We experienced 10 abortions and 21 live births from our 23 recipients and 2 abortions and 7 live births in 7 recipients from other transplant center. The live birth rate was 8.9 per 1000 female transplant recipients of childbearing age. Seven recipients received either treatments of artificial insemination or in vitro fertilization. Average age at pregnancy was 33.2 ± 3.2 years old, and the fertile period post-transplantation was longer in recipients with live births than those without live births (14.1 ± 7.1 vs 9.9 ± 7.3 years, P .05). In 42.9% of recipients with live birth, pregnancy-induced hypertension was observed in the last trimester. The gestational age and the average birth weight were 32.8 ± 5.0 months and 2184 ± 632 g, respectively. During follow-up of 14.5 years, there was one case of graft loss, which is a rate of 2.5 per 1000 female recipients.Although pregnancy complications are often observed in kidney recipients, graft survival is less influenced by pregnancy. Importantly, kidney disease at childbearing age disrupts pregnancy even after kidney transplantation.

Background Transplant recipients are supposedly in a more anemic, catabolic, and even inflammatory state at re-entering hemodialysis due to chronic rejection. The goal of this study was to clarify how transplant recipients can re-enter dialysis safely by focusing on control of anemia. Methods From 2012 to 2014, a total of 29 transplant recipients re-entered hemodialysis because of chronic rejection (ie, the chronic kidney disease with transplant [CKDT] group). At the same time, in 2014, a total of 30 patients with chronic kidney disease without transplantation entered dialysis as the control group (ie, the CKD group). CKDT recipients (mean ± standard deviation age, 41.9 ± 11.8 years; 18 male subjects, 10 female subjects; frequency of diabetes, 10%; duration of graft survival, 12.5 ± 4.3 years) were younger and fewer had diabetes compared with the CKD group (age, 53.2 ± 10.5 years; 21 male subjects, 9 female subjects; frequency of diabetes, 36%). Patient characteristics at entering dialysis in both groups were analyzed according to retrospective chart review. Results At entering dialysis, there were no significant differences between the CKD and CKDT groups in terms of the following: dose of darbepoetin; concentrations of hemoglobin, albumin, and C-reactive protein; cardiothoracic ratio; blood urea nitrogen and creatinine levels; estimated glomerular filtration rate; initial ultrafiltration; and duration of hospitalization for initiation of dialysis. The only difference between groups was mean weight at entry to dialysis (CKDT group, 58.5 ± 15.1 kg; CKD group, 67.1 ± 14.8 kg; P = .03). The darbepoetin dose per kilogram of weight did not differ between groups (CKDT, 2.28 ± 2.03 μg/kg; CKD, 2.12 ± 1.6 μg/kg; P = .95) in the final month before entry to dialysis. Conclusions Safe re-initiation of dialysis is important for recipient survival. Although anemia is supposedly higher in transplant recipients due to immunosuppression, this single-center analysis found no difference in anemia in CKD with or without transplantation, caused by good use of erythropoietin-stimulating agents in both groups.

OBJECTIVES To evaluate long-term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30-year period. METHODS We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975-2009. Patients were stratified according to the immunosuppressive regimen (era 1: methylprednisolone and azathioprine; era 2: calcineurin inhibitor-based therapy, including methylprednisolone and azathioprine or mizoribine; era 3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil). RESULTS The median age and bodyweight at transplantation were 9.7 years and 20.6 kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1 year post-transplant decreased significantly from 61.0% in era 1 to 14.5% in era 3 (P

Aim Erythropoiesis-stimulating agent (ESA) treatment during the predialysis period can be a strategy to reduce cardiac mortality soon after initiation of dialysis. In this study, we compared the efficacy of continuous erythropoietin receptor activator (CERA) and darbepoetin alfa (DA) in patients with chronic kidney disease (CKD) over 6 months prior to initiation of dialysis. Methods This study was a retrospective propensity score-matched study conducted at a single center in Japan that analyzed the effects of CERA and DA therapy on haemoglobin (Hb) changes, ESA resistance index (ERI) changes, and interval of ESA administration during a 6-month observation period prior to initiation of dialysis. Propensity scores were used for matching the patients included in the CERA and DA groups. Results Among 680 screened, 74 pairs of patients (one in each group) were included in the present analysis after propensity score matching. Mean Hb significantly decreased over 6 months in the DA group compared to that in the CERA group (−0.70 ± 0.23 vs. –0.33 ± 0.22). In the DA group, mean ERI was significantly increased at 4, 3, 2, and 1 month before dialysis and initiation of dialysis, while in the CERA group, mean ERI was significantly increased only at 1 month before dialysis and initiation of dialysis. Moreover, patients administered CERA were required to visit the hospital significantly less frequently for ESA administration than those administered DA. Conclusion Our study showed that CERA may be more effective than DA for management of anaemia during the predialysis period in CKD patients.

Aneurysm of autogenous arteriovenous fistula is a common complication in patients receiving hemodialysis. We present a novel method for repair of a case of aneurysm of arteriovenous fistula resulting from stenosis. A 52-year-old woman presented with aneurysm formation of the left upper arm arteriovenous fistula, with related numbness in the left hand. Clinical examination revealed a tense, pulsatile aneurysm above the brachiocephalic anastomosis. Ultrasound examination revealed an aneurysm (50 mm × 25 mm) with proximal stenosis and an arteriovenous fistula flow rate above 1200 mL/min. An incision was made lateral to the aneurysm from the brachiocephalic anastomosis to the proximal stenosis through the antecubital fossa. After exposure of the entire aneurysmal arteriovenous fistula, the narrowed segment, and the proximal cephalic vein, the aneurysm outflow was ligated and the narrowed segment was removed. A U-shaped incision was made on the aneurysm to create an aneurysmal flap (75 mm × 20 mm). The flap was tubularized after calibration of the lumen with a 14-Fr cannula. End-to-end anastomosis was performed between the distal tubularized flap and the proximal cephalic vein. Intra- and postoperative arteriovenous fistula flow rates were below 900 mL/min. After surgery, the remodeled arteriovenous fistula was immediately usable for hemodialysis with normal arteriovenous fistula flow in the upper arm. The repair technique achieved not only aneurysmorrhaphy but also created an autologous vascular graft as the bypass after removal of the narrowed segment. Moreover, this technique achieved reduced arterial inflow and is suitable for patients with conditions similar to those of this case.

We examined the clinicopathologic significance of hyalinosis in the vasa recta in the medulla of allograft kidney biopsies. We analyzed biopsy specimens from January 2010 to December 2015, obtained from both the cortex and medulla (including the vasa recta) ≥ 1 year after living-donor kidney transplantation. We excluded biopsy specimens from recipients who had undergone transplantation due to diabetic nephropathy or who had diabetes mellitus after transplantation. We evaluated hyaline arteriolopathy in the cortex using the aah score determined by the Banff 2007 classification. Among 381 biopsy specimens obtained from 248 transplant recipients ≥ 1 year after transplantation, 36 specimens obtained from 34 recipients showed vasa recta hyalinosis (VRH) in the medulla. Among these 36 specimens, 17 had a score of aah3, 16 had a score of aah2, and 3 had a score of aah1. The incidence of VRH was 1.9% at ≥ 1 to

AIM Epstein syndrome is a hereditary disease characterized by macrothrombocytopaenia and progressive nephritis. The abnormality of the MYH9 gene has a strong relationship to the severity of the disease. Severe Epstein syndrome progresses to end-stage renal disease rapidly after adolescence. There is no established therapy. We sought to clarify appropriate management of Epstein syndrome nephropathy. METHODS Epstein syndrome patients who underwent renal transplantation at our institution between March 2009 and March 2017 were enrolled. Epstein syndrome was diagnosed based on clinical features and genetic testing. Patient medical records were reviewed retrospectively. RESULTS Four male patients with Epstein syndrome, all with severe MYH9 gene mutations (p.R702C in three and p.S96L in one), were enrolled. Despite treatment with renin-angiotensin system blockers, nephropathy was refractory and progressed rapidly, and the patients required dialysis or renal transplantation after adolescence. Early preparation for treatment based on early and accurate diagnosis of Epstein syndrome enabled two patients to undergo pre-emptive renal transplantation. For these patients, we kept the platelet count above 100 × 109 /L until day 7 after renal transplantation with platelet transfusions for macrothrombocytopaenia, and no postoperative bleeding episodes occurred. CONCLUSION Epstein syndrome nephropathy due to a severe MYH9 gene mutation can be refractory and progress rapidly; therefore, early and accurate diagnosis is important for safer therapeutic options including pre-emptive renal transplantation. By keeping the platelet count above 100 × 109 /L during the perioperative period, renal transplantation can be a safe treatment option for severe Epstein syndrome nephropathy.

Caregivers of patients with chronic kidney disease experience great burdens. Changes in these caregivers’ quality of life (QOL) before and after their children underwent kidney transplantation (KTx) were evaluated in this prospective study. The sequential QOL scores of 31 caregivers (median age 38.5 years) whose children (5.8 years) underwent KTx from 2012 to 2014 were studied. The same questionnaires were administered before and 1, 3, and 12 months after KTx. We evaluated whether the following factors were associated with QOL: pre-transplant dialysis, recipient’s mental and/or motor disability, and acute rejection or infections after KTx. The average QOL score before KTx (3.40) was higher than that of the general population (3.23). Despite a temporal decrease at 1 month (3.15), the final QOL scores were maintained at 3 months (3.40) and 1 year (3.42) after KTx. The mean QOL scores were significantly higher for caregivers of patients with than without dialysis before KTx [3.46 vs. 3.28 (p = 0.041) at 3 months and 3.53 vs. 3.18 (p = 0.001) at 1 year, respectively]. Conversely, these scores were significantly lower for caregivers of patients with than without disabilities [2.97 vs. 3.20 (p = 0.021) at 1 month, 3.18 vs. 3.46 (p = 0.006) at 3 months, and 3.10 vs. 3.50 (p = 0.001) at 1 year, respectively]. Dialysis of children before KTx was a particularly larger burden for caregivers. The child’s comorbidities and social adaptation problems might be focused after KTx, we need to evaluate for more long-term QOL of caregivers.

Renal anemia is a complication of chronic kidney disease. Guidelines for safe and effective treatment in patients with renal anemia are needed. The Japanese Society for Dialysis Therapy (JSDT) published guidelines for the treatment of renal anemia in chronic hemodialysis patients in 2004 and in hemodialysis, peritoneal dialysis, predialysis, and pediatric patients in 2008. These two publications provide excellent guidance with respect to clinical practice issues, including the definition and diagnosis of renal anemia, the criteria for the initiation of treatment, target hemoglobin levels, iron supplementation therapy, blood transfusion, and side effects. The guidelines significantly improved the treatment of renal anemia in Japan. However, since 2008, many studies have assessed the treatment of renal anemia, and erythropoiesis-stimulating agents (ESAs) are now available. Therefore, the Executive Board of the JSDT decided that it was time to revise the guidelines to make them more appropriate to the situation of chronic kidney disease patients in Japan. This is the third edition of the guidelines for renal anemia published by the JSDT. The purpose is to improve the prognosis of chronic kidney disease patients, including after renal transplantation, through the treatment of renal anemia. The intended users of the guidelines are all healthcare professionals engaged in the treatment of chronic kidney disease. Regarding the treatment of adult dialysis and predialysis patients, statements and commentary are provided in the context of answers to clinical questions in Chapter 2 (Target Hb level and criteria for starting renal anemia treatment) and Chapter 4 (Evaluation of iron status and iron therapy). Furthermore, the essential information is provided alongside the critical issues in Chapter 1 (Diagnosis of renal anemia), Chapter 3 (Administration of ESAs—administration route and dose), Chapter 5 (ESA hyporesponsiveness), Chapter 6 (Side effects and concomitant symptoms of ESAs), and Chapter 7 (Red blood cell transfusion). In addition, the treatment of pediatric patients and post-renal transplant patients is discussed in Chapter 8 and Chapter 9, respectively.

Post-transplant recurrent nephritis is the third common complication that leads to graft loss, which affects the long-term graft survival of kidney transplant patients. Immunoglobulin A nephropathy (IgAN) is the most common for recurrent nephritis, with a recurrence rate of 13–53%. In this study, 12 patients diagnosed with recurrent IgAN were divided into two groups, one which underwent tonsillectomy and another which did not, to analyze the effect of treating IgAN recurrent with or without tonsillectomy. Urinary findings, estimated GFR (eGFR), and histopathological alteration (Banff and Oxford classifications) were examined for >5 years after kidney transplantation. We found that tonsillectomy protected graft function and prevented pathological alterations. The levels of urinary proteins increased in the no tonsillectomy group, whereas no difference was observed in the severity of hematuria between two groups. eGFR declined and mesangial hypercellularity score increased in the no tonsillectomy group. Tonsillectomy not only results in a favorable clinical outcome but also protects against the histological damage caused by recurrent IgAN after kidney transplantation.

RTx of adult-size kidneys presents a size mismatch in small pediatric recipients, and there are potential surgical complications. This study reveals the outcomes of intra- and extraperitoneal RTx in low-weight (less than 15 kg) pediatric recipients. We studied 51 pediatric patients weighing less than 15 kg who received a living-related donor renal transplant between 2009 and 2017. The intraperitoneal (group A, n = 24) and extraperitoneal (group B, n = 27) approaches were compared. In group A, the mean age, Ht, and weight were 3.8 ± 1.6 years, 83.7 ± 6.5 cm, 10.5 ± 1.8 kg; in group B, 5.0 ± 1.9 years, 95.3 ± 7.3 cm, and 13.0 ± 1.4 kg. Single renal artery grafts (21 in group A and 16 in group B) and double renal artery grafts (three in group A and 11 in group B) were performed. Of the patients with double renal artery transplants, one in group A and six in group B underwent ex vivo arterial reconstruction. The eGFR (mL/min/1.73 m2 ) at 1-week post-transplant in group A was significantly higher than that in group B; the eGFRs at 4 weeks post-transplant did not differ. One graft was lost in group B because of vascular thrombosis. Post-transplant complications included ileus and transplant ureteral stenosis. There was no significant difference in 5-year graft survival rate (group A 100%, group B 91.7%). Both transplant approaches are feasible to adapt to a size mismatch between the adult-size donor kidney and low-weight pediatric recipients.

Some children with steroid-sensitive nephrotic syndrome (SSNS) have been reported to suffer relapses in adulthood, but the clinical course of such adults is unclear. Four children with SSNS suffered relapses after 30 years of age. Those 4 patients developed frequently relapsing nephrotic syndrome (NS) between 2 and 10 years of age. They were treated with prednisolone (PSL) combined with cyclophosphamide in 3 patients, mizoribine in 2, and cyclosporine in 1 during childhood, and with cyclosporine in 2 during adulthood. After 20 years of age, the frequency of relapses gradually decreased. The last relapse occurred between 33 and 39 years of age, and proteinuria disappeared within 1 month after the start of treatment with PSL. At the last follow-up, all 4 patients continued to receive PSL, had normal renal function, and were in complete remission of NS when they were between 33 and 41 years of age. Although the long-term outcome of SSNS is usually considered to be favorable, pediatricians should be aware that some children with SSNS may require long-term treatment during adulthood.

Objective Body mass index (BMI) is commonly used for assessment of nutritional status. However, changes in BMI in chronic kidney disease (CKD) patients are affected not only by muscle and fat but also by fluid volume. The ratio of extracellular water (ECW BIA ) to total body water (TBW BIA ) in multifrequency bioelectrical impedance analysis is commonly used for assessing abnormal fluid status. This study reexamines ECW BIA /TBW BIA and evaluates the reliability of TBW BIA /TBW watson and dry mass index (DMI) in the assessment of fluid and nutritional status. Design, Setting, and Subjects TBW BIA , intracellular water (ICW BIA ), and ECW BIA were measured in 45 randomly selected CKD patients. Participants were surveyed for age, gender, BMI, blood pressure, serum albumin, estimated glomerular filtration rate, and proteinuria. DMI was calculated by the formula ([weight − TBW BIA ]/height 2 ) and TBW BIA /TBW watson using an anthropometric formula (Watson). Fluid and nutritional status were assessed using ECW BIA /TBW BIA , TBW BIA /TBW watson , and DMI. Results TBW BIA /TBW watson positively correlated with weight, BMI, and diastolic blood pressure and negatively correlated with age and serum albumin level. In contrast, ECW BIA /TBW BIA correlated with ICW deficit, aging, and body weight loss. On the basis of DMI and TBW BIA /TBW watson , participants were categorized as follows: 1 obese patient with hypovolemia and 2 with euvolemia; 17 overweight patients with hypovolemia (n = 6), euvolemia (n = 8), or hypervolemia (n = 3); 24 patients of optimal weight with hypovolemia (n = 10), euvolemia (n = 9), or hypervolemia (n = 5); and 1 underweight patient with euvolemia. Conclusions A combination of DMI, BMI, and TBW BIA /TBW watson makes it possible to include assessment of fluid volume to the physique index. In addition, ECW BIA /TBW BIA is not a reliable marker of edematous state in CKD patients.

Reduced dietary protein intake in malnourished patients with chronic kidney disease (CKD) may be associated with adverse clinical outcomes, which may mask any efficacy of a low-protein diet. The study included 126 patients with CKD who attended a dedicated dietary counseling clinic in 2005–2009 and were systematically followed until January 2015. Of these patients, 20 (15.9%) had moderate or severe nutrition-related risk of geriatric nutritional risk index (GNRI) < 92; these patients were more likely to be older, have a greater proteinuria, and have lower body mass index and serum albumin concentration. Dietary protein intake was significantly lower in older patients (r = −0.33, p < 0.001) and those with lower glomerular filtration rate (r = 0.47, p < 0.001). The non-protein to nitrogen calorie ratio was independently associated with GNRI. Reduced GNRI was significantly associated with mortality (hazard ratio (HR) = 4.94; 95% confidence interval (CI) = 1.61–15.42, p = 0.012) and cardiovascular events (HR = 9.37; 95% CI = 2.49–37.34, p = 0.006), but not with adverse renal outcomes. Restricting protein intake may be harmful to patients with any nutrition-related risk, suggesting that improvement of nutritional status should be a high priority.

Background/Aim: Fluid volume overload occurs in chronic kidney disease (CKD), leading to the compensatory release of natriuretic peptides. However, the elevated cardiac peptides may also be associated with malnutrition as well as volume overload. Methods: Body fluid composition was measured in 147 patients with CKD between 2009 and 2015, and its relationship to brain natriuretic peptide (BNP) levels was examined. Body fluid composition was separated into three components: (a) a water-free mass consisting of muscle, fat, and minerals; (b) intracellular water (ICW) content, and (c) extracellular water (ECW) content. Excess fluid mass was calculated using Chamney's formula. Results: The measured BNP levels in the tertile groups were 10.9 ± 5.4, 36.3 ± 12.5, and 393 ± 542 pg/ml, respectively. Patients in a higher log-transformed BNP level tertile were more likely to be older, to have a higher frequency of cardiac comorbidities, pulse pressure, C-reactive protein levels, and proteinuria, and to have lower serum sodium, kidney function, and serum albumin (p < 0.05). In body fluid composition, decreased body mass was significantly associated with the ECW-to-ICW ratio in relation to the downward ICW slope (r = -0.235, p = 0.004) and was strongly correlated with excess fluid mass (r = -0.701, p < 0.001). The ECW-to-ICW ratio and excess fluid mass was independently associated with the BNP levels. Conclusion: Fluid volume imbalance between intra- and extracellular water regulated by decreased cell mass was independently associated with BNP levels, which may explain the reserve capacity for fluid accumulation in patients with CKD.

Fluid imbalance due to sodium retention and malnutrition can be characterized by the ratio of extracellular water (ECW) to intracellular water (ICW). We investigated whether the ECW/ICW ratio is a risk factor for adverse outcomes.Retrospective cohort study.149 patients with chronic kidney disease from 2005 to 2009, who were followed until August 2013.Body fluid composition was measured by bioelectrical impedance analysis. Patients were categorized according to the ECW/ICW ratio tertile. Daily nutrient intake was estimated from 24-h dietary recall and analyzed using standard food composition tables. The main outcomes were adverse renal outcomes, as defined by a decline of 50% or more from the baseline glomerular filtration rate or initiation of renal replacement therapy, cardiovascular events, and all-cause mortality.The ECW/ICW ratio increased with downward ICW slope with age and renal dysfunction besides ECW excess with massive proteinuria. Sodium intake, protein intake, and calorie intake were negatively correlated with the ECW/ICW ratios due to the steeper decreasing ICW content with the decreased dietary intake than the decreasing ECW content. During a median 4.9-year follow up, patients in the highest tertile had the worst adverse renal outcomes (15.9 vs. 5.1 per 100 patient-years, P0.001), cardiovascular events (4.1 vs. 0.3 per 100 patient-years, P = 0.002), and mortality (11.2 vs. 1.3 per 100 patient-years, P0.001). The adjusted hazard ratio (95% confidence intervals) for adverse renal outcomes, cardiovascular events, and mortality were 1.15 (1.03 - 1.26), 1.12 (0.93 - 1.31), and 1.29 (1.11 - 1.50), respectively.Fluid imbalance between ICW and ECW occurring in malnourished and elderly patients with chronic kidney disease may explain the reserve capacity for volume overload and is associated with adverse renal outcomes and all-cause mortality.

Aim: Angiotensin-converting enzyme 2 (ACE2) is a type I membrane protein that antagonizes the action of angiotensin II. Because of the need for invasive kidney biopsy, little is known about the role of renal ACE2 in human kidney diseases. The authors studied if urinary ACE2 could provide a novel clue to renal ACE2 in chronic kidney disease (CKD). Methods: Subjects were 190 patients with CKD including 38 patients with diabetic nephropathy and 36 healthy subjects. Parameters were urinary ACE2 by enzyme-linked immunosorbent assay, blood pressure, casual plasma glucose, proteinuria, microalbuminuria, serum creatinine and estimated glomerular filtration rate. Urine and serum samples were also subjected to western blotting of ACE2. Results: Western blotting confirmed increased urinary ACE2 levels in patients with CKD. Urinary ACE2 was significantly higher in patients with CKD than healthy subjects (median 9.64 (interquartile range, 4.41–16.89) vs 1.50 (0.40–2.33) mg/g·creatinine, P

We discuss a renal transplant patient with focal segmental glomerulosclerosis (FSGS) treated with plasma exchange and rituximab. A 45-yr-old woman underwent cadaveric renal transplantation in May 2008. She had started hemodialysis support in 1991. Immediately after transplantation, massive proteinuria (1-5 g/d) appeared. Graft biopsy at one h showed minor glomerular abnormalities with partial foot process effacement on electric microscopy. Protocol biopsy at three months after transplantation for persistent proteinuria showed obvious FSGS under light microscopy. Plasma exchange and rituximab administration were subsequently initiated in August 2008, and proteinuria disappeared within a month after starting these treatments. Protocol graft biopsy one yr after transplantation (2009) showed increased global sclerosis and a decrease in segmental sclerosis. In addition, foot process effacement had recovered by one yr after transplantation. Plasma exchange and subsequent rituximab administration led to clinical remission of post-transplant FSGS with improvement in podocyte structure. Rituximab should be considered soon after several sessions of plasmapheresis in transplant patients with recurrent FSGS.

We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN) before and after tonsillectomy. A 36-year-old man started on hemodialysis support in 1996 due to biopsy-proven IgAN, living related renal transplantation was then performed in 1997. Six years after transplantation, the patient presented with microhematuria and proteinuria. Graft biopsy for these urinary abnormalities showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003, proteinuria remitted 6 months after the tonsillectomy and microhematuria disappeared three years later. Protocol graft biopsy was subsequently performed twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing the findings of the pre-tonsillectomy biopsy and the two post-tonsillectomy biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of the mesangial matrix and proliferation of mesangial interposition in 2008. In addition, global sclerosis of glomeruli increased over time, the area of tubulointerstitial damage has extended as well. While the tonsillectomy led to clinical remission of recurrent IgAN, the chronicity progressed on these protocol biopsies. This is the first report of the efficacy and the limitations of tonsillectomy in a case of recurrent IgAN in a transplant patient.

A girl and her mother were diagnosed as having membranoproliferative glomerulonephritis (MPGN) type I. Microscopic hematuria and proteinuria presented at 9 years of age in the mother and at 14 years in the daughter. Both had persistent hypocomplementemia and were treated with steroids. When the mother was 40 years old, proteinuria was still continuing and creatinine clearance was 64.4 ml/min per 1.73 m(2). When the daughter was 15 years old, microscopic hematuria was still continuing. To our knowledge, familial cases of MPGN in two generations have not been reported in Japan.

Angiotensin-converting enzyme (ACE) 2 (ACE2) is expressed mainly in the heart and kidney and forms angiotensin-1-7 from angiotensin II. ACE2 might act in a counterregulatory manner to ACE. There is little information about renal ACE and ACE2 expression in human diabetic nephropathy.Cross-sectional study.Kidney tissue from 20 patients with type 2 diabetes and overt nephropathy and 20 healthy kidney donors.Diabetes status.Renal expression of ACE and ACE2 assessed by means of immunohistochemistry and in situ hybridization. Correlation between ACE and ACE2 expression and levels of various biochemical parameters.Decreased ACE2 and increased ACE expression in both the tubulointerstitium and glomeruli resulted in a significant (P0.001) increase in ACE/ACE2 ratio in patients with diabetes with overt nephropathy compared with controls, although ACE messenger RNA in the tubulointerstitium did not significantly increase. ACE/ACE2 ratio correlated positively with values for mean blood pressure, fasting blood glucose, serum creatinine, proteinuria, and hemoglobin A(1c) and inversely with estimated glomerular filtration rate (P0.001).Inclusion of small number of human renal biopsy specimens with structural distortion of cortical tissue.The high ACE/ACE2 ratio in kidneys of patients with type 2 diabetes with overt nephropathy may contribute to renal injury.

症例は62歳，男性．既往歴として1年前に胸部食道癌で開胸開腹の手術歴がある．某年11月8日腹痛を主訴として当院を受診した．腹部CTでは大腸の拡張像を認め，腸閉塞の診断で入院となった．イレウス管を挿入し保存的加療を行ったが，入院後6日目より腹満の増悪，発熱，呼吸困難を認め，胸腹部CTを行ったところ，左気胸，横行結腸の左胸腔内への脱出を認め，胸腔内での大腸穿孔と診断し，緊急手術を行った．食道裂孔より胸腔内に横行結腸が約40cm脱出し，虚血性壊死により2カ所で穿孔していた．脱出した横行結腸を切除し，人工肛門造設，開胸開腹ドレナージ術を行った．術後はエンドトキシン吸着，人工呼吸器管理を行った．術後膿胸の加療を必要としたが，術後98病日に退院することができた．食道切除後に胸腔内で大腸穿孔をきたした症例は稀である．胸腔内での大腸穿孔例について若干の文献的考察を加えて報告する．

症例は22歳，女性．下腹部痛を主訴に近医を受診し，腹腔内出血の診断にて当院3次救急搬送された．腹部造影CTにて左卵巣の嚢胞性病変および周囲血管からの造影剤漏出，腹腔内出血を認めた．入院後経時的に貧血の進行を認め，緊急手術の方針となったが，術前胸部単純X線写真，CTにて左胸水も認め，胸腔ドレーンを挿入し，血胸と診断した．全身麻酔下に腹腔鏡下手術を開始し，出血部は左卵巣嚢腫破裂部であり，嚢腫摘出を施行した．胸腔ドレーン血性排液は650ml，腹腔内出血は500mlであり，両者の性状は同じであった．血胸の原因が不明のため，術後胸腔ドレーンよりウログラフィンによる胸腔造影を施行したところ，腹腔内への造影剤漏出を認め，左横隔膜に小孔の存在が推測された．本症例では腹腔内出血による腹圧上昇と呼吸運動による胸腔内の陰圧により腹腔内出血が横隔膜小孔を通じて胸腔内に引き込まれたものと考えられ，本邦報告例ではこれまで1例のみで非常に稀な病態であった．

症例は66歳, 男性. 右肺上葉腺癌c-T2N0M0 stage IBに対して, 右肺上葉切除+ND2aを施行し, 順調に経過していたが, 術後3日目の血液検査にてWBC500と急激な白血球減少, 血小板も9.3万と減少し, 同日夜間より38.4度の発熱を認めた. まず血液内科と相談し, 術中術後の薬剤性の再生不良性貧血, もしくは感染による播種性血管内凝固症候群 (DIC) を疑い, メシル酸ガベキサート (1000mg/day), G-CSF製剤を開始した. その後WBC220, Neut0%となり, 術後6日目に骨髄穿刺を施行し, 骨髄の低形成, 組織球による著明な血球貪食像を認め, 血球貪食症候群 (以下HPS) と診断された. 同日よりメチルプレドニゾロン1,000mg/dayを3日間のステロイドパルス療法を開始し, 以後プレドニン漸減療法に以降した. ステロイド投与開始後6日目より徐々に白血球, 血小板は増加し, 8日目に正常化した. 術後15日目の再骨髄穿刺では骨髄は正形成となり, 貪食像も消失した. 本邦における外科手術後のHPS発症報告例は本症例を含め12例であり, 文献的考察を加え報告する.