School urinary screening program in Japan: history, outcomes, perspectives.

In Japan, pediatric urinary screening in schools for asymptomatic hematuria and proteinuria began in 1974 and has been very successful in detecting asymptomatic kidney diseases at an early stage. While the American Academy of Pediatrics recommended discontinuing urinalysis as a public health service in 2007, urinary screening in Japan has proven extremely successful in reducing the incidence of kidney failure with replacement therapy in children and young adults, especially through the early treatment of glomerulonephritis, such as immunoglobulin A nephropathy. Furthermore, the positivity rate on urinary screening in Japan is significantly lower than in the United States where the rate of false positive results is typically very high. Japan's seamless and efficient pediatric urinary screening may be a helpful example for other countries as well. However, the present investigation revealed several, unresolved problems with the system. For example, the methods used varied in terms of their cutoff point, additional examinations, and types of detailed testing. In Japan, various urinary screening methods are being tested to optimize the system for national use. Recently, the authors also recommended a system of detailed examinations, including beta-2 microglobulin testing and ultrasonography, to detect congenital anomalies of the kidney and urinary tract, the most common, underlying disease in kidney failure with replacement therapy, which is often overlooked until the symptoms have become grave. While school urinary screening has been ongoing for about 50 years and should be continued, improvements should also be made to it as needed.

Reference blood pressure values obtained using the auscultation method for 2-year-old Japanese children: from the Japan Environment and Children's Study.

BACKGROUND: Reference blood pressure (BP) values for Japanese children based on a large number of measurements by auscultation have not yet been established. METHODS: This was a cross-sectional analysis of data from a birth-cohort study. The data from the sub-cohort study conducted for children at the age of 2 years in the Japan Environment and Children's Study from April 2015 to January 2017 were analyzed. BP was measured via auscultation using an aneroid sphygmomanometer. Each participant was measured in triplicate, and the average value of two consecutive measurements with a difference of less than 5 mmHg was recorded. The reference BP values were estimated using the lambda-mu-sigma (LMS) method and compared with those obtained via the polynomial regression model. RESULTS: Data from 3361 participants were analyzed. Although the difference between the estimated BP values by the LMS and the polynomial regression model was small, the LMS model was more valid based on the results of the fit curve of the observed values and regression models for each model. For 2-year-old children with heights in the 50th percentile, the 50th, 90th, 95th, and 99th percentile reference values of systolic BP (mmHg) for boys were 91, 102, 106, and 112, and that for girls were 90, 101, 103, and 109, respectively, and those of diastolic BP for boys were 52, 62, 65, and 71, and that for girls were 52, 62, 65, and 71, respectively. CONCLUSION: The reference BP values for 2-year-old Japanese children were determined based on auscultation and were made available.

Analysis of the ratio of urinary beta-2-microglobulin to total protein concentration in children with isolated tubulointerstitial disease.

BACKGROUND: Proteinuria is broadly classified into glomerular and tubular proteinuria. Urinary beta-2-microglobulin (ß2-MG) is known as a marker for detecting tubulointerstitial diseases. However, tubulointerstitial damage can also lead to an increase in urinary ß2-MG level in some patients with glomerular diseases. This study aimed to determine the ratio of urinary ß2-MG to total protein (TP) concentration in patients with both isolated tubulointerstitial and glomerular disease. METHODS: This multicenter, retrospective study included children with Dent disease or lupus nephritis in five facilities. Their urinary ß2-MG levels were > 1000 µg/L. Urinary ß2-MG and TP concentrations were obtained, and the ratio of urinary ß2-MG to TP concentration (µg/mg) was calculated. The Mann-Whitney U test was performed to compare this ratio between these children. The optimal cutoff value of the ratio for considering the presence of glomerular disease was obtained from the receiver operating characteristic (ROC) curve. RESULTS: We obtained information on 23 children with Dent disease and 14 children with lupus nephritis. The median ratios of urinary ß2-MG to TP concentrations in children with Dent disease and lupus nephritis were 84.85 and 1.59, respectively. The ROC curve yielded the optimal cutoff value of this ratio for distinguishing between these diseases, and the cutoff value was found to be 22.3. CONCLUSION: In children with tubulointerstitial diseases, the urinary ß2-MG concentration may be approximately 8.5% of the TP concentration. The possibility of presenting with glomerular disease should be considered in patients with a ratio of urinary ß2-MG to TP concentration of < 22.3 (µg/mg).

Medical and psychosocial outcomes in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

BACKGROUND: Adolescents and young adults face various socio-emotional and behavioral challenges that can affect their medical and psychosocial outcomes. Pediatric patients with end-stage kidney disease (ESKD) often have extra-renal manifestations, including intellectual disability. However, limited data are available regarding the impact of extra-renal manifestations on medical and psychosocial outcomes among adolescents and young adults with childhood-onset ESKD. METHODS: Patients born between January 1982 and December 2006 that had developed ESKD in 2000 and later at age < 20 years were enrolled in this multicenter study in Japan. Data for patients' medical and psychosocial outcomes were retrospectively collected. Associations between extra-renal manifestations and these outcomes were analyzed. RESULTS: In total, 196 patients were analyzed. The mean age at ESKD was 10.8 years, and at last follow-up was 23.5 years. The first modality of kidney replacement therapy was kidney transplantation, peritoneal dialysis, and hemodialysis in 42, 55 and 3% of patients, respectively. Extra-renal manifestations were documented in 63% of patients and 27% had intellectual disability. Baseline height at kidney transplantation and intellectual disability significantly impacted final height. Six (3.1%) patients died, of which five (83%) had extra-renal manifestations. Patients' employment rate was lower than that in the general population, especially among those with extra-renal manifestations. Patients with intellectual disability were less likely to be transferred to adult care. CONCLUSIONS: Extra-renal manifestations and intellectual disability in adolescents and young adults with ESKD had considerable impacts on linear growth, mortality, employment, and transfer to adult care.

Depression and health-related quality of life in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

BACKGROUND: Patient survival and physical outcomes among children with end-stage kidney disease (ESKD) have significantly improved, and recent research has focused on long-term depression symptoms and health-related quality of life (HRQOL). However, no studies have been conducted among adolescents and young adults with childhood-onset ESKD in Japan. METHODS: This multicenter study included 45 adolescents and young adults aged 16-39 years who developed ESKD at age < 20 years. Depression symptoms were measured using the Beck Depression Inventory (BDI)-II. The Short Form-36 Health Survey (SF-36) was used to assess HRQOL. Factors associated with depression and HRQOL were analyzed. RESULTS: Depression (BDI-II score ≥ 14) was observed in 13 (29%) patients. Patient's SF-36 physical component summary (PCS) and mental component summary (MCS) scores were comparable with those for the general population. Lower estimated glomerular filtration rate, higher BDI-II scores, and lower body mass index were associated with lower PCS scores. BDI-II scores were negatively correlated with MCS scores. We observed a trend that unemployment was associated with lower MCS scores. CONCLUSIONS: Depression is frequently observed among adolescents and young adults with childhood-onset ESKD. Regular screening for psychosocial concerns, maintaining stable graft functions, and achieving optimal nutritional status may contribute to improved well-being among these patients.

Early predictive factors for progression to kidney failure in infants with severe congenital anomalies of the kidney and urinary tract.

BACKGROUND: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. METHODS: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded. RESULTS: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. CONCLUSIONS: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis.

Background: Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients. Methods: This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients' clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates. Results: The distribution of histologic variants according to the Columbia classification was 45% (n=53) FSGS not otherwise specified, 21% (n=25) cellular, 15% (n=18) perihilar, 13% (n=16) collapsing, and 6% (n=7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P<0.001). Conclusions: We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS.

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.

Ultrasonographic reference values and a simple yet practical formula for estimating average kidney length in Japanese children.

BACKGROUND: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants. METHODS: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis. RESULTS: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]". CONCLUSION: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established.

Validation of the estimated glomerular filtration rate equation for Japanese children younger than 2 years.

BACKGROUND: We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFRUemura). The eGFR equation is for children aged 2-18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFRunder 2). The aim of the present study was to validate this new equation. METHODS: We collected the data of 13 patients from previous studies and compared the results of eGFRunder 2, eGFRUemura, and updated eGFR developed by Schwartz (eGFRSchwartz) with measured GFR using mean error (ME), root mean square error (RMSE), P30 and Bland-Altman analysis. RESULTS: The ME of eGFRunder 2, eGFRUemura and eGFRSchwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m2, respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland-Altman bias analysis showed fan-shape. The eGFRunder 2 equation was the most accurate in the three equations. CONCLUSION: The eGFRunder 2 equation was useful for Japanese children younger than 2 years.

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.

Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of steroid-resistant nephrotic syndrome.

BACKGROUND: Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. METHODS: Seventy patients aged 1-15 years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post-transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A. RESULTS: Data from 36 kidney transplant recipients were analyzed. Twenty-two (61%) patients experienced post-transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p = .01). CONCLUSION: This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A may predict post-transplant SRNS recurrence.

A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40-44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome.

BACKGROUND: Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). RESULTS: TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. CONCLUSIONS: Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.

Influenza virus vaccination in pediatric nephrotic syndrome significantly reduces rate of relapse and influenza virus infection as assessed in a nationwide survey.

Although vaccination may precipitate relapses of nephrotic syndrome (NS) in children with idiopathic NS, no data are available regarding NS activity regarding influenza (flu) virus infections and NS relapses after receiving inactivated flu vaccines. We conducted a nationwide study of children aged 6 months to 15 years with idiopathic NS to assess the relationship between NS relapse, flu vaccination, and flu infections. We used a multivariate Poisson regression model (MPRM) to calculate the risk ratio (RR) for flu infection and for NS relapse in children with and without flu vaccination. Data of 306 children were assessed. The MPRM in all 306 children showed a significantly lower RR for flu infection (RR: 0.21, 95% confidence interval CI 0.11-0.38) and for NS relapse (RR: 0.22, 95% CI 0.14-0.35) in children receiving flu vaccination compared with unvaccinated children. In an additional MPRM only among 102 children receiving flu vaccination, they had a significantly lower risk for NS relapse during the post-vaccination period (RR: 0.31. 95% CI 017-0.56) compared with the pre-vaccination period. Although our study was observational, based on the favorable results of flu vaccinations regarding flu infections and NS relapse, the vaccine may be recommended for children with NS.

Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry.

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

Prognosis and acute complications at the first onset of idiopathic nephrotic syndrome in children: a nationwide survey in Japan (JP-SHINE study).

BACKGROUND: Information on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce. METHODS: The Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients' prognosis in this cohort. RESULTS: We obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8-9.4] and a median follow-up period of 4.1 years (IQR 2.5-5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin <1.0 g/dL) and severe bacterial infection were not independent factors, but female sex {hazard ratio [HR] 1.5 [95% confidence interval (CI) 1.1-1.7]} and hypertension [HR 4.0 (95% CI 2.6-6.0)] were significantly related to AKI. During the observation period, ocular hypertension requiring treatment occurred in 17.4% of patients, among which 0.4% received surgical treatment. Progression to frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome in 3 years was seen in 44.2% of the patients and was shown by the Cox regression analysis to be significantly related to younger age and days until remission at the first episode, but not to sex, hematuria, the minimum serum albumin level or AKI. Two patients died during the observation period. One patient showed progression to end-stage kidney disease. CONCLUSION: Based on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory.