Water intake, baseline biopsy, and graft function after living donor kidney transplantation.

Increased water intake is recommended for kidney transplant recipients; however, its efficacy remains controversial. We hypothesized that pre-existing histological findings of the allograft might modulate the impact of water intake. We retrospectively analyzed 167 adults with living-donor kidney transplants (April 2011-May 2020; median observation period, 77 months) whose baseline biopsy data were available. We compared the chronic-change group (n = 38) with the control group (n = 129) to assess the impact of self-reported daily water intake on the estimated glomerular filtration rate (eGFR). The range distribution of water intake was as follows: - 1000 ml (n = 4), 1000-1500 ml (n = 23), 1500-2000 ml (n = 64), 2000-2500 ml (n = 57), 2500-3000 ml (n = 16), and 3000 - ml (n = 3). Donor age was significantly higher in the chronic-change group. In the control group, the ΔeGFR/year increase was correlated with water intake. However, the increase in the water intake of the chronic-change group significantly decreased ΔeGFR/year (1000-1500 ml: + 1.95 ml/min/1.73 m2 and > 2000 ml: - 1.92 ml/min/1.73 m2, p = 0.014). This study suggested a potential influence of increased water intake on recipients with marginal grafts in living donor kidney transplantation.

Light Chain Deposition Disease Recurrence in Renal Allograft after Long-Term Remission.

Light chain deposition disease (LCDD) is a rare manifestation of monoclonal gammopathy, which can lead to renal failure. We previously reported a detailed recurrence process in a case of LCDD after renal transplantation. To the best of our knowledge, no report has described the long-term clinical course and renal pathology findings of recurrent LCDD in patients after renal transplantation. In this case report, we describe the long-term clinical presentation and changes in renal pathology of the same patient after early LCDD relapse in a renal allograft. A 54-year-old woman with recurrent immunoglobulin A λ-type LCDD in an allograft was admitted 1 year post-transplant for bortezomib and dexamethasone therapy. At 2 years post-transplantation, a graft biopsy performed after complete remission was achieved, showing some glomeruli with residual nodular lesions similar to the pre-treatment renal biopsy findings. However, the enlarged subendothelial space disappeared. She remained in complete remission serologically for 6 years. Subsequently, the ratio of serum κ/λ-free light chains decreased gradually. She underwent a transplant biopsy approximately 12 years after renal transplantation due to increased proteinuria and decreased renal function. Compared with the previous graft biopsy, almost all glomeruli showed advanced nodule formation and subendothelial expansion. Because the LCDD case relapsed after long-term remission following renal transplantation, protocol biopsy monitoring might be necessary.

Initiation of renin-angiotensin system inhibitors and first complete remission in patients with primary nephrotic syndrome: a nationwide cohort study.

BACKGROUND: Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. METHODS: This cohort study included 84 adults (median age, 65 years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5 years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR. RESULTS: Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced first CR (incidence rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR] 2.27, 95% confidence interval [CI] 1.06-4.84), and lower (aIRR: 0.17, 95% CI 0.04-0.68) first CR in patients with membranous nephropathy and other pathologies, respectively. CONCLUSION: RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy.

Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. METHODS: We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. RESULTS: Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR<90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). CONCLUSIONS: Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.

A rare case of proliferative glomerulonephritis with monoclonal IgG2 kappa deposit: a case report.

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a rare monoclonal gammopathy of renal significance with dense deposits of monoclonal immunoglobulin. CASE PRESENTATION: We report a 78-year-old Japanese male patient with mild proteinuria and lower extremity edema. Monoclonal immunoglobulin could not be identified in his serum or urine. Although his bone marrow biopsy was negative, renal biopsy found features of membranoproliferative glomerulonephritis (MPGN) with deposition of monoclonal IgG2 kappa. Electron microscopy examination revealed non-organized electron-dense deposits in the subepithelial, and subendothelial mesangial regions. Steroid monotherapy was performed after diagnosis of PGNMID but complete remission was not achieved. CONCLUSION: PGNMID with IgG3 kappa deposits is the most common in cases with the histological feature of MPGN. There are few cases of PGNMID with IgG2 kappa deposits exhibiting MPGN. This report describes a very rare case of PGNMID with the histological feature of MPGN.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Clinicopathological discordance in biopsy-proven nephrosclerosis: a nationwide cross-sectional study of the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: Patients with nephrosclerosis display heterogenous clinical phenotypes, often leading to a clinical diagnosis discordant with pathological nephrosclerosis diagnosis. However, little is known about clinical factors associated with clinicopathological discordance of biopsy-proven nephrosclerosis. METHODS: In a cross-sectional study of 891 patients with biopsy-proven nephrosclerosis registered in the Japan Renal Biopsy Registry (J-RBR) between July 2007 and June 2016, we examined clinical characteristics associated with a pre-biopsy clinical diagnosis discordant with pathological nephrosclerosis diagnosis using multivariable logistic regression with adjustment for relevant clinical characteristics. RESULTS: Overall, the mean (SD) age was 58.6 (13.7) years; 67.6% of patients were male; and 63.2% were on antihypertensive drugs. The median estimated glomerular filtration rate (eGFR) was 43.8 mL/min/1.73 m2 and the median proteinuria was 0.5 g/day. Of the 891 patients, 497 (55.8%) had a clinical diagnosis discordant with pathological nephrosclerosis diagnosis, with chronic nephritic syndrome being the most common (> 75%) discordant clinical diagnosis. After multivariable adjustment, age (odds ratio 1.34, [95% confidence interval, 1.16-1.55], per 10 years increase), eGFR (1.10 [1.00-1.21], per 10 mL/min/1.73 m2 increase), and proteinuria (1.20 [1.03-2.16], per 1 g/day decrease) were found to be significantly associated with the clinicopathological discordance. CONCLUSIONS: Patients with older age, higher eGFR, and lower proteinuria had significantly higher likelihood of being clinically diagnosed with other glomerular disease in patients with biopsy-proven nephrosclerosis. Our findings highlight the heterogeneous clinical phenotypes of nephrosclerosis and suggest the need for continuous improvement of clinical diagnostic accuracy as well as for wider kidney biopsy indications for nephrosclerosis.

Adult Living-Donor Kidney Transplantation, Donor Age, and Donor-Recipient Age.

INTRODUCTION: Owing to organ shortage, the number of kidney transplantation (KT) involving older adult living donors is increasing. We aimed to investigate the effects of living-donor age and donor-recipient age differences on KT outcomes. METHODS: This single-center, retrospective cohort study involved 853 adult LDKTs performed between January 2008 and December 2018. Recipients were stratified into the following 5 groups based on donor age and donor-recipient age difference: donor age, 30 to 49 years and age difference, -10 to 15 years; donor age, 50 to 69 years and age difference, -10 to 15 years; donor age, 50 to 69 years and age difference, 15 to 40 years; donor age, 70 to 89 years and age difference, -10 to 15 years; and donor age, 70 to 89 years and age difference, 15 to 40 years (groups 1, 2, 3, 4, and 5, respectively). As a primary outcome, the risk of graft loss was investigated. The secondary outcomes were postoperative estimated glomerular filtration rates (eGFRs) and mortality rates of recipients. RESULTS: Group 4, representing KT between older adult donors and older adult recipients, had the highest graft loss risk and mortality. The eGFRs of the recipients from donors aged 70 to 89 years (groups 4 and 5) were significantly lower than those from donors in the other groups. Although the differences in the eGFR between groups 4 and 5 were not significant, the eGFR of group 4 was lower than that of group 5 at 6 months post-KT. CONCLUSION: LDKTs from older adult donors to older adult recipients resulted in the worst graft survival and mortality rates.

Nationwide Survey of Post-Transplant Glomerular Diseases, Based on the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND Nationwide data on allograft kidney biopsies have been limited in number, in contrast to the large amount of accumulated data on native kidney biopsies. In this context, we have surveyed transplant biopsy data based on the nationwide database, the Japan Renal Biopsy Registry (J-RBR). MATERIAL AND METHODS A total of 2430 transplant biopsy cases were registered in the web-based J-RBR from January 2007 to January 2018. We categorized the entries regarding both the purpose of the biopsy and pathological diagnosis, and confirmed transplant glomerular diseases based on the clinical and pathological diagnosis. RESULTS Of the 2430 total transplant biopsy cases, 637 cases, including 9 cases of baseline biopsy, 216 cases of protocol biopsy, and 232 cases of episode biopsy, had a pathological diagnosis, including glomerular diseases, rejection, calcineurin inhibitor nephropathy, and interstitial fibrosis and tubular atrophy. Of these, 127 cases presented with glomerular disease, including 8 cases of baseline biopsy, 23 of protocol biopsy, 59 of episode biopsy, and 37 of unknown purpose). A total of 127 biopsies with glomerular disease revealed a high prevalence of immunoglobulin A nephropathy (n=38, 29.9%), followed by mesangial proliferative glomerulonephritis (n=29, 22.8%) and focal segmental glomerulosclerosis (n=8, 6.3%) when focused on protocol and episode biopsies. CONCLUSIONS The nationwide transplant biopsy database demonstrated the pathological characteristics of 637 cases, including 127 cases of post-transplant glomerular disease. The protocol and episode biopsies included high prevalence rates of IgAN, followed by FSGS.

Incidence and factors associated with prescribing renin-angiotensin-system inhibitors in adult idiopathic nephrotic syndrome: A nationwide cohort study.

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

The effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study.

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single-center randomized, double-blind, placebo-controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1-month posttransplant. The primary endpoint was the change in eGFR from baseline to 12-month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12-month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m2 (95% CI; -0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m2 (95% CI, -0.02 to 3.7) in the placebo group, with no significant between-group difference (-0.7 mL/min/1.73 m2 [95% CI; -3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR <45 mL/min/1.73 m2 (Pinteraction <0.05, between-group difference; -4.3 mL/min/1.73 m2 [95% CI; -7.3 to -1.3]). The degree of IFTA, changes in urine albumin-to-creatinine ratio, or adverse events including hypercalcemia and infections requiring hospitalization did not differ between groups. In conclusion, cholecalciferol supplementation did not affect eGFR change compared to placebo among incident KTRs. These findings do not support cholecalciferol supplementation for improving allograft function in incident KTRs. Clinical trial registry: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000020597 (please refer to the links below). UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023776.

A Case of Recurrent Atypical Anti-Glomerular Basement Membrane Nephritis Suspicion after Renal Transplantation.

Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM antibody but show linear glomerular basement membrane staining for immunoglobulin. We present a 69-year-old man who underwent a living-donor kidney transplant. The aetiology of the renal failure was a focal segmental glomerulonephritis-like lesion resistant to immunosuppressive therapy. A renal graft biopsy revealed diffuse endocapillary hypercellularity, and mild mesangiolysis with linear GBM staining for IgG. The patient was diagnosed with atypical anti-GBM nephritis since the patient tested negative for circulating anti-GBM antibodies. Treatment involved intravenous methylprednisolone, plasma exchange, and rituximab administration. Protocol graft biopsy performed 1 year after the renal transplant showed a focal segmental glomerulonephritis-like lesion possibly progressing from endocapillary hypercellularity and mesangiolysis. These findings were similar to his native kidney biopsy findings. Although classical recurrent anti-GBM nephritis is rare when a renal transplant is performed after decreased disease activity, this case was considered as a case of recurrent atypical anti-GBM nephritis after renal transplant.

Study of Glomerulopathy in Donors after Kidney Transplantation.

INTRODUCTION: Living kidney donation improves the lives of individuals with kidney failure; however, recent studies have suggested that living kidney donors may be at a relatively higher risk of reduced renal function than healthy non-donors. We therefore aimed to evaluate the clinical and pathological findings in living kidney donors who developed kidney disease. METHODS: From January 1991 to May 2019, 1,625 live kidney donations were performed at our hospital. Among the donors, 7 developed kidney disease after donation and underwent open renal biopsy. We studied the clinical and pathological findings of these patients from their clinical records. RESULTS: There were 3 patients with immunoglobulin A (IgA) nephropathy, 2 with membranous nephropathy, 1 with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, and 1 with secondary focal segmental glomerulosclerosis (FSGS). All patients with IgA nephropathy had latent IgA deposition on their baseline biopsy. One patient with membranous nephropathy demonstrated findings of membranous nephropathy on the baseline biopsy, despite being asymptomatic. All patients, except for those with ANCA-associated nephropathy and secondary FSGS, recovered from the nephritis or maintained an adequate renal function after treatment. DISCUSSION/CONCLUSION: Baseline biopsy is necessary for assessing the renal condition of kidney donors, and these donors require long-term follow-up based on their baseline biopsy findings. If donors develop kidney disease, appropriate diagnosis and treatment are essential.

Mid-Term Outcomes After Treatment for Antibody-Mediated Rejection by De Novo Donor-Specific HLA Antibody in Renal Transplant Recipients: Does Early Treatment Lead to Better Outcomes?

BACKGROUND: De novo donor-specific HLA antibody (DSA) and antibody-mediated rejection (ABMR) are strongly associated with late allograft loss in renal transplant recipients. However, the impact of therapeutic intervention with the current treatment options for ABMR remains unclear. This study aimed to elucidate the efficacy of treatment for ABMR. METHODS: Sixty-seven patients who had de novo DSAs underwent diagnostic biopsy for ABMR, and these patients were classified into 3 groups: ABMR-free group (n = 40), clinical ABMR group (n = 15), and subclinical ABMR group (n = 12). The ABMR-positive groups were treated mainly with double-filtration plasmapheresis followed by rituximab and corticosteroid pulse. The patient characteristics and graft outcomes were compared between groups. RESULTS: The clinical and subclinical ABMR groups were younger and had a higher number and mean fluorescence intensity (MFI) of de novo DSAs than the ABMR-free group. The graft survival in the clinical ABMR group was significantly lower than that in the ABMR-free group, but the subclinical ABMR group had a surprisingly good graft survival rate compared to the ABMR-free group (43.3% vs 100% vs 94.2% 5 years after diagnostic biopsy in the clinical ABMR, subclinical ABMR, and ABMR-free groups, respectively, P < .001). CONCLUSIONS: Our findings indicated that early therapeutic intervention for patients with de novo DSAs may improve graft survival.

Better remission rates in elderly Japanese patients with primary membranous nephropathy in nationwide real-world practice: The Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. PATIENTS AND METHODS: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. RESULTS: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. CONCLUSION: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

Medullary Cystic Kidney Disease and Focal Segmental Glomerulosclerosis Caused by a Compound Heterozygous Mutation in TTC21B.

Mutations in the TTC21B gene have been identified in patients with nephronophthisis and were recently found in some patients with focal segmental glomerulosclerosis. We herein report a Japanese boy with end-stage renal disease due to medullary polycystic kidney disease and primary focal segmental glomerulosclerosis. Next-generation sequencing detected a new compound heterozygous missense mutation in the TTC21B gene. His renal pathological findings and gene mutations have not been previously reported in patients with ciliopathy. For children with severe renal dysfunction, mutations in the TTC21B gene cause both ciliopathy characterized by bilateral polycystic kidney disease and primary focal segmental glomerulosclerosis.

Preoperative Comorbidities and Outcomes of Medically Complex Living Kidney Donors.

INTRODUCTION: Recent reports have described an increased risk of renal disease in living kidney donors compared with the general population. However, these reports do not detail the outcomes of medically complex living donors (MCLDs) with preoperative comorbidities (PCs), such as hypertension, dyslipidemia, glucose intolerance, and obesity. Analysis of living donors with end-stage renal disease (ESRD) has shown that these PCs may contribute significantly to the development of ESRD. We aimed to evaluate the effect of PCs on postoperative renal function and mortality in MCLDs. METHODS: Between January 2008 and December 2016, 807 living-donor kidney transplants were performed in our unit. Of these, 802 donors completed postoperative follow-up of >5 months. Donors were stratified into 4 groups based on the number of PCs present: healthy living donors (HLDs) with no PCs (n = 214) or MCLDs with 1 PC (n = 302), 2 PCs (n = 196), or 3 PCs (n = 90) (denoted MCLD [PC 1], MCLD [PC 2], or MCLD [PC 3], respectively). We compared pathology observation data from baseline biopsy, postoperative estimated glomerular filtration rate (eGFR), postoperative urinary protein concentration, and mortality between HLD and MCLD groups. RESULTS: Interstitial fibrosis, tubular atrophy, glomerulosclerosis, and arteriolosclerosis were more frequent in MCLDs (PC 3) than in HLDs. No significant differences were identified between HLDs and MCLDs in terms of postoperative eGFR and short-term mortality. Overt proteinuria and ESRD were not observed. CONCLUSIONS: Appropriate postdonation management of MCLDs with PCs may result in similar outcomes as for HLDs.

Factors related to suboptimal recovery of renal function after living donor nephrectomy: a retrospective study.

BACKGROUND: The renal function of the remaining kidney in living donors recovers up to 60~70% of pre-donation estimated-glomerular filtration rate (eGFR) by compensatory hypertrophy. However, the degree of this hypertrophy varies from donor to donor and the factors related to it are scarcely known. METHODS: We analyzed 103 living renal transplantations in our institution and divided them into two groups: compensatory hypertrophy group [optimal group, 1-year eGFR ≥60% of pre-donation, n = 63] and suboptimal compensatory hypertrophy group (suboptimal group, 1-year eGFR < 60% of pre-donation, n = 40). We retrospectively analyzed the factors related to suboptimal compensatory hypertrophy. RESULTS: Baseline eGFRs were the same in the two groups (optimal versus suboptimal: 82.0 ± 13.1 ml/min/1.73m2 versus 83.5 ± 14.8 ml/min/1.73m2, p = 0.588). Donor age (optimal versus suboptimal: 56.0 ± 10.4 years old versus 60.7 ± 8.7 years old, p = 0.018) and uric acid (optimal versus suboptimal: 4.8 ± 1.2 mg/dl versus 5.5 ± 1.3 mg/dl, p = 0.007) were significantly higher in the suboptimal group. The rate of pathological chronicity finding on 1-h biopsy (ah≧1 ∩ ct + ci≧1) was much higher in the suboptimal group (optimal versus suboptimal: 6.4% versus 25.0%, p = 0.007). After the multivariate analysis, the pathological chronicity finding [odds ratio (OR): 4.8, 95% confidence interval (CI): 1.3-17.8, p = 0.021] and uric acid (per 1.0 mg/dl, OR: 1.5, 95% CI: 1.1-2.2, p = 0.022) were found to be independent risk factors for suboptimal compensatory hypertrophy. CONCLUSION: Chronicity findings on baseline biopsy and higher uric acid were associated with insufficient recovery of the post-donated renal function.

Lower incidence of de novo donor-specific antibodies against HLA-DR in ABO-incompatible renal transplantation.

Recently, in vitro experiments have demonstrated that anti-blood group A/B antibody binding to endothelial cells induce a protective effect against antibody-mediated injury. This study aimed to clarify the potential clinical benefit of ABO incompatibility in donor-specific HLA antibody (DSA)-induced chronic antibody-mediated rejection (ABMR). We enrolled 215 ABO-incompatible renal transplant (ABO-I) and 467 ABO-identical/compatible renal transplant recipients (ABO-Id/C). The prevalence of de novo DSA production and incidence of biopsy-proven chronic ABMR were compared between the two groups. The incidence of DR-associated de novo DSA was significantly lower in ABO-I than in ABO-Id/C (P = 0.028). Diagnostic biopsy for ABMR was conducted in 54 patients (11 ABO-I and 43 ABO-Id/C). Biopsy-proven chronic ABMR was lower in ABO-I than in ABO-Id/C (27.3% [3/11] vs. 44.2% [19/43]) patients. Our findings suggest that ABO incompatibility may cause low production of DR-associated de novo DSA, possibly resulting in a reduced incidence of chronic ABMR.