Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Nail-patella syndrome with nephropathy in a de novo LMX1B mutation: triangular lunula of the thumb and lack of finger creases as clues.

Nail-patella syndrome (NPS) is an autosomal dominant disease caused mostly by mutations in the LMX1B gene and is characterized by hypoplastic nails, hypoplastic patella, elbow deformities, glaucoma, and nephropathy, sometimes leading to kidney failure. The combination and the severity of symptoms vary greatly from patient to patient. Because a kidney biopsy may show nonspecific findings, patients with nephropathy alone may not be diagnosed without undergoing genetic testing. We examined the case of a 6-year-old girl with persistent high proteinuria who was not diagnosed by kidney biopsy but had a diagnosis of a de novo mutation in the LMX1B gene following genetic testing. Retrospectively, only the thumbs showed triangular lunulae, while the third and fourth fingers lacked skin creases over the distal interphalangeal joints, which is subtle but characteristic of NPS. Notifying pediatric nephrologists of these findings can help avoid unnecessary kidney biopsies and lead to early detection of the disease.

Renal pathology in adult and paediatric population of Japan: review of the Japan renal biopsy registry database from 2007 to 2017.

BACKGROUND: The Japan Renal Biopsy Registry (J-RBR), a nationwide, web-based, registry system, started in 2007. This study aimed to summarise the epidemiology of biopsy-diagnosed kidney disease in Japan over 10 years. METHODS: We analysed the J-RBR database, from 2007 to 2017. Patients' clinical data collected at the time of biopsy and histopathological diagnoses were used for epidemiological and clinicopathologic analyses. RESULTS: The predominant renal biopsy diagnoses were immunoglobulin A nephropathy (39.2%), lupus nephritis (6.5%) and minimal change disease (6.0%) in younger adults (19-64 years), and membranous nephropathy (17.4%), antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis (13.0%), and immunoglobulin A nephropathy (12.5%) in older adults (≥ 65 years). The percentages of patients diagnosed with membranoproliferative glomerulonephritis and immunoglobulin A nephropathy decreased, whereas those with immunoglobulin A vasculitis and diabetic nephropathy increased over the decade. In paediatric patients (< 19 years), immunoglobulin A nephropathy (36.1%), minimal change disease (17.6%), and immunoglobulin A vasculitis (8.6%) were the predominant diagnoses. The percentage of patients diagnosed with immunoglobulin A vasculitis increased over the decade. Based on the sex distribution, minimal change disease and membranous nephropathy were predominant in men aged < 20 and > 40 years, respectively, whereas immunoglobulin A vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis were predominant in women in their 20s and 30s and aged < 50 years, respectively. Immunoglobulin A nephropathy was predominant in men at most ages and in women in their 20s to 40s. CONCLUSIONS: This study describes the distribution and changes in kidney biopsy diagnoses over 10 years in Japan and paves the way for future research on kidney diseases in adults and children.

International cohort of 382 children with lupus nephritis - presentation, treatment and outcome at 24 months.

BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Factors related to ultrafiltration volume with icodextrin dialysate use in children.

BACKGROUND: Icodextrin has a lower absorption rate, and icodextrin peritoneal dialysate contributes to more water removal than glucose dialysate in patients with high peritoneal permeability. There are limited data on icodextrin dialysate use in children. METHODS: This study included all pediatric patients who received peritoneal equilibration tests and peritoneal dialysis with icodextrin dialysate at the study center. The factors related to ultrafiltration volume with icodextrin dialysate with long dwell time were statistically analyzed. Then the ultrafiltration volume with icodextrin and medium-concentration glucose dialysate was compared in individual cycles in the same patients. RESULTS: Thirty-six samples were included in the icodextrin group, and nine samples were used to compare the ultrafiltration volume with icodextrin and glucose dialysate. Dwell time, D/P-creatinine, D/D0-glucose, age, height, and weight correlated significantly with the ultrafiltration volume of icodextrin dialysate (p < 0.05). A dwell volume equal to or more than 550 mL/m2 was associated with a significantly higher ultrafiltration volume than a lower dwell volume (p = 0.039). Multiple regression analysis revealed that dwell time (p = 0.038) and height (p < 0.01) correlated with ultrafiltration volume significantly. In addition, the ultrafiltration volume was superior (p < 0.01), and dwell time was longer (p = 0.02), with icodextrin dialysate than with medium-concentration glucose dialysate. CONCLUSIONS: The ultrafiltration volume with icodextrin dialysate decreases in patients with small stature. Providing sufficient dwell time and volume is important for maximal water removal even in children. Ultrafiltration volume is superior with icodextrin than medium-concentration glucose dialysate for long dwell times. A higher resolution version of the Graphical abstract is available as Supplementary information.

Epidemiology of biopsy-proven Henoch-Schönlein purpura nephritis in children: A nationwide survey in Japan.

BACKGROUND: Little is known about the epidemiology of Henoch-Schönlein purpura nephritis (HSPN). METHODS: We conducted a nationwide epidemiological survey of Japanese children aged 1 to 15 years with HSPN. Children who were newly diagnosed with HSPN by biopsy between January 2013 and December 2015 were eligible for the survey to clarify the incidence of HSPN. We also conducted an institutional survey on kidney biopsy criteria and treatment protocols. RESULTS: A total of 353 of 412 institutions (85.7%) responded to the questionnaire. Of the 353 institutions, 174 reported to perform kidney biopsies at their institutions, and 563 children were diagnosed with HSPN. Considering the collection rate, the estimated incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year. The median age at biopsy was 7.0 years, and the male-to-female ratio was 1.2:1. The kidney biopsy criteria and treatment protocols for HSPN were as follows. Patients with acute kidney injury underwent biopsy at least one month after onset. For patients without kidney dysfunction, the timing for biopsy was determined by the amount of proteinuria. Regarding the treatment of HSPN, there were certain commonalities among the treatment protocols, they eventually differed depending on the institutions involved. CONCLUSIONS: The incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year in Japan. The male-to-female ratio and date of diagnosis of HSPN were similar to those in previous studies. The kidney biopsy criteria and treatment protocols for HSPN varied among institutions. Further studies are warranted to establish an optimal treatment policy based on the prognosis.

Half of children with IgA vasculitis-associated nephritis with nephrotic state spontaneously recover.

BACKGROUND: The clinical spectrum of Henoch-Schönlein purpura nephritis (HSPN), now known as IgA vasculitis-associated nephritis (IgAVN), ranges from isolated microscopic haematuria to nephrotic syndrome, progressive glomerulonephritis, and kidney failure. The outcome also varies, and the management of IgAVN is controversial. The presence of nephrotic state at disease onset is thought to be a risk factor of a poor prognosis. However, not all patients with nephrotic state have a poor prognosis, and it is unclear whether they need early treatment. METHODS: We herein retrospectively examined the clinical course of paediatric IgAVN cases with nephrotic state (serum albumin [sAlb]<3.0 g/dL and urine protein-creatinine ratio of >2.0 g/ gCr) without kidney injury treated at our hospital between 2010 and 2018. RESULTS: Of the 216 patients with IgAVN identified, 17 met the inclusion criteria. The median follow-up period from disease onset to the last observation was 40.5 months (IQR:31.0-74.2). Eleven patients were male, the median age at onset was 5 years, the minimum serum Alb level was 1.9 g/dL, the maximum proteinuria value was 12.3 g/gCr, and the median minimum eGFR was 86.0 mL/min/1.73 m2 in the acute phase. Eight patients (47%) achieved resolution of nephrotic state within 3 months and complete remission without treatment by the last observation. The patients with spontaneous resolution of nephrotic state had less severe hypoalbuminaemia (Alb<2.0 g/dL) and tended to show a quick increase in the serum albumin level. CONCLUSIONS: Our study found that half of paediatric patients with IgAVN with nephrotic state achieved spontaneous resolution without treatment and enjoyed a favourable short-term outcome. Consideration of the duration of nephrotic state and trends in the serum albumin level in children with IgAVN may allow unnecessary kidney biopsies and immunosuppressive therapy to be avoided.

Comprehensive genetic analysis using next-generation sequencing for the diagnosis of nephronophthisis-related ciliopathies in the Japanese population.

Nephronophthisis is an autosomal-recessive kidney disease that is caused by abnormalities in primary cilia. Nephronophthisis-related ciliopathies (NPHP-RCs) are a common cause of end-stage kidney disease (ESKD) in children and adolescents. NPHP-RCs are often accompanied by extrarenal manifestations, including intellectual disability, retinitis pigmentosa, or polydactyly. Although more than 100 causative genes have been identified, its diagnosis is difficult because the clinical features of each mutation often overlap. From September 2010 to August 2021, we performed genetic analysis, including next-generation sequencing (NGS), in 574 probands with kidney dysfunction and retrospectively studied cases genetically diagnosed with NPHP-RCs. RESULTS: We detected mutations related to NPHP-RCs in 93 patients from 83 families. Members of 60 families were diagnosed using NGS, and the mutations and the corresponding number of families are as follows: NPHP1 (24), NPHP3 (10), OFD1 (7), WDR35 (5), SDCCAG8 (4), BBS10 (3), TMEM67 (3), WDR19 (3), BBS1 (2), BBS2 (2), IFT122 (2), IFT140 (2), IQCB1 (2), MKKS (2), SCLT1 (2), TTC21B (2), ALMS1 (1), ANKS6 (1), BBS4 (1), BBS12 (1), CC2D2A (1), DYNC2H1 (1), IFT172 (1), and MAPKBP1 (1). A total of 39 cases (41.9%) progressed to ESKD at the time of genetic analysis, whereas 58 cases (62.3%) showed extrarenal manifestations, the most common being developmental delay, intellectual disability, and autism spectrum disorder in 44 patients. Comprehensive genetic analysis using NGS is useful for diagnosing patients with NPHP-RCs.

Incidence of malignancy after pediatric kidney transplantation: a single-center experience over the past three decades in Japan.

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.

Comparison of inulin clearance with 2-h creatinine clearance in Japanese pediatric patients with renal disease: open-label phase 3 study of inulin.

BACKGROUND: There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients. METHODS: Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m2 × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin). RESULTS: Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study. CONCLUSIONS: The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease. CLINICALTRIALS. GOV IDENTIFIER: NCT03345316.

Genotype-Phenotype Correlation in WT1 Exon 8 to 9 Missense Variants.

INTRODUCTION: WT1 missense mutation in exon 8 or 9 causes infantile nephrotic syndrome with early progression to end-stage kidney disease (ESKD), Wilms tumor, and 46,XY female. However, some patients with missense mutations in exon 8 or 9 progress to ESKD in their teens or later. Therefore, we conducted a systematic review and functional analysis of WT1 transcriptional activity. METHODS: We conducted a systematic review of 174 cases with WT1 exon 8 or 9 missense variants from our cohort (n=13) and previous reports (n=161). Of these cases, mild and severe genotypes were selected for further in vitro functional analysis using luciferase assay. RESULTS: The median age of developing ESKD was 1.17 years. A comparative study was conducted among three WT1 genotype classes: mutations of the DNA-binding site (DBS group), mutations outside the DNA-binding site but at sites important for zinc finger structure formation by 2 cysteines and 2 histidines (C2H2 group), and mutations leading to other amino acid changes (Others group). The DBS group showed the severest phenotype and the C2H2 group was intermediate, whereas the Others group showed the mildest phenotype (developing ESKD at 0.90, 2.00, and 3.92 years, respectively, with significant differences). In vitro functional analysis showed dominant-negative effects for all variants; in addition, the DBS and C2H2 mutations were associated with significantly lower WT1 transcriptional activity than the other mutations. CONCLUSION: Not only the DNA-binding site but also C2H2 zinc finger structure sites are important for maintaining WT1 transcriptional activity, and their mutation causes severe clinical symptoms.

Mean of creatinine clearance and urea clearance examined over 1 h estimates glomerular filtration rate accurately and precisely in children.

AIM: Accurate and precise estimation of glomerular filtration rate (GFR) is essential in kidney disease. We evaluated the usefulness of the mean of creatinine clearance (CCr ) and urea clearance (CUN ) examined over a 1-h urine collection period (1-h (CCr + CUN )/2) in a retrospective, cross-sectional study across two centres, as a relatively simple method for estimating GFR in children. METHODS: Children aged ≤18 years who underwent inulin clearance (CIn ) tests were eligible. Two clearance values were obtained during a 2-h test consisting of two periods of 1 h each. The mean clearance in two periods was defined as 1-h clearance. 1-h (CCr + CUN )/2, 1-h CCr , 1-h CUN and GFR estimated by Cr-based and cystatin C (CysC)-based formulas for Japanese children were compared with CIn . Bland-Altman plots were used to evaluate correlations. The primary outcome measure was the correlation between 1-h (CCr + CUN )/2 and CIn . RESULTS: Fifty-three children were analysed. Their median age was 10.9 (interquartile range [IQR] 5.3-14.2) years, and median CIn and 1-h (CCr + CUN )/2 were 77.0 (IQR: 51.5-95.1) and 81.0 (IQR: 64.1-97.7) ml/min/1.73 m2 , respectively. Percentage difference of CIn and 1-h (CCr + CUN )/2 in the Bland-Altman plot was -11.2% (95% confidence interval - 15.3% - -7.1%), with 95% lower and upper limits of agreement of -40.3% and 18.0%, respectively. Thus, 1-h (CCr + CUN )/2 was 1.12 times CIn . CONCLUSION: 1 h (CCr + CUN )/2 was almost concordant with CIn . 1-h (CCr + CUN )/2 can estimate GFR accurately and precisely, making it a simple and speedy test for use in clinical practice.

A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2.

Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.

Clinical and histological features in pediatric and adolescent/young adult patients with renal disease: a cross-sectional analysis of the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR). METHODS: This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age < 15 years) and 6,532 AYA (age 15-30 years) patients. RESULTS: Although chronic nephritic syndrome was the most common clinical diagnosis at age > 5 years, nephrotic syndrome was the most frequent diagnosis at age < 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age. CONCLUSION: To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients.

Successful High-dose Chemotherapy in Combination With Autologous Peripheral Blood Stem Cell Transplantation in an Anuric Child With Neuroblastoma.

No reports describe high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (auto-PBSCT) in pediatric patients with neuroblastoma and end-stage renal disease. Here, we report the case of a patient with high-risk neuroblastoma who developed anuria during treatment. HDCT with auto-PBSCT under hemodialysis, with strict attention to the ultrafiltration volume and dose modification of alkylating agents, was performed. Although the first auto-PBSCT led to engraftment failure, the second auto-PBSCT resulted in successful myeloid engraftment 8 months after anuria. This case demonstrated that HDCT with auto-PBSCT can be safely performed in children with renal failure under hemodialysis.

Increasing bladder capacity and vesicoureteral reflux in pediatric kidney transplant patients.

OBJECTIVES: To investigate the frequency of vesicoureteral reflux, and the relationship of pretransplant decreased bladder capacity and post-transplant vesicoureteral reflux in children undergoing kidney transplantation. METHODS: A voiding cystourethrography was carried out in 172 pediatric kidney transplantation recipients before, and 4 months after, transplantation to evaluate bladder capacity and vesicoureteral reflux. The correlation of post-transplant vesicoureteral reflux with pretransplant bladder capacity, vesicoureteral reflux in the native kidney and the method of ureteral reimplantation (intravesical/extravesical) was analyzed. Atrophic bladder was defined as having ≤50% functional bladder capacity (age in years + 2) × 25 (mL) or ≤150 mL in patients aged >10 years. RESULTS: Bladder capacity increased remarkably after transplantation in both post-transplant vesicoureteral reflux- group (from 180 to 253 mL) and vesicoureteral reflux+ group (from 82 to 171 mL). Voiding cystourethrography showed vesicoureteral reflux in 12 cases of kidney transplantation (7%; grade 1: 2, grade 2: 3, grade 3: 7). Pretransplant atrophic bladder was an independent risk factor of post-transplant vesicoureteral reflux (P = 0.004, hazard ratio 9.5). There was no difference in renal function between the vesicoureteral reflux- group and vesicoureteral reflux+ group at 4 months to 5 years post-transplantation. CONCLUSIONS: Pretransplant atrophic bladder is a risk factor of post-transplant vesicoureteral reflux in pediatric patients. However, bladder capacity can remarkably increase after transplantation, and kidney function in the post-transplant vesicoureteral reflux+ group is stable.

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan.

BACKGROUND: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan. METHODS: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease. RESULTS: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys-Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy. CONCLUSIONS: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices. TRIAL REGISTRATION: Not applicable.

Clinical Accuracy of Average Creatinine and Cystatin-C-Based Estimated GFR in Japanese Living Renal Transplantation Donors.

OBJECTIVE: To evaluate the clinical accuracy of several estimated glomerular filtration rates (eGFR) using cystatin-C to measure renal function in Japanese renal donors. METHODS: In total, 61 healthy, potential renal donors were assessed. The average age was 42.7 years (range: 27-67). We evaluated the GFR based on the 24-hour creatinine clearance (Ccr) using 24-hour urine collection, eGFR based on serum creatinine (eGFRcr), and cystatin-C (eGFRcys) levels using an equation developed by the Japanese Society of Nephrology, the average of the eGFRcr and eGFRcys (eGFRave) rates, and an eGFR based on a combination of serum creatinine and cystatin-C values using an equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The association between Ccr and each eGFR was evaluated using Pearson's r and the Bland-Altman plot. RESULTS: Pearson's correlation coefficient analysis revealed a significant correlation between the Ccr and the eGFRcr (r = 0.62, P < .0001), eGFRave (r = 45, P = .0003), and eGFRcr-cys (r = 0.451, P = .0014). The Bland-Altman study suggested that each eGFR had a low level of agreement with the Ccr because the latter was higher than each eGFR. On the other hand, the eGFRave had the highest level of agreement with CCr × 0.715. CONCLUSIONS: The eGFRave may provide a simple and useful method of evaluating renal function in living renal transplant donors.