Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial.

BACKGROUND: To investigate the long-term outcome in children with frequently relapsing nephrotic syndrome (FRNS) we conducted a follow-up of a previous randomized controlled trial (RCT) 10 years after the initiation of the treatment protocol. METHODS: We previously conducted an RCT on the efficacy of cyclosporine for treating children with FRNS. After 2 years of treatment, a recommended a management protocol of steroids, and immunosuppressants was provided. RESULTS: Valid information was available for 46 of the 56 patients (82.1 %) enrolled in the original RCT. The median follow-up period was 10.3 years from the start of protocol treatment with cyclosporine. At last follow-up (mean age 18.7 years), only ten patients (21.7 %) showed disease-free remission (no relapse for at least 2 years). In contrast, 23 (50.0 %) continued to relapse frequently or were on immunosuppressants, eight patients (17.4 %) had infrequent relapses without immunosuppressants. Adverse effects attributable to treatment included short stature (6 patients), osteoporosis (six patients), obesity (4 patients), cataracts (3 patients) and hypertension (3 patients). No lethal event or renal dysfunction occurred during follow-up. CONCLUSIONS: This 10-year follow-up study shows that most children with FRNS experience relapses after 2 years of cyclosporine treatment, in adolescence and into adulthood. Outcomes in terms of life expectancy and renal function are favorable.

High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia.

OBJECTIVES: Thrombocytopenia is sometimes observed during linezolid therapy. Here, we aimed to investigate the factors affecting linezolid-induced thrombocytopenia. METHODS: A prospective observational study was performed between October 2009 and February 2011; 30 patients were included. Plasma linezolid trough concentrations were measured on days 3, 7 and 14 after initial drug administration. Platelet counts and haemoglobin levels were also monitored. RESULTS: Thrombocytopenia occurred in 17 patients (56.7%). Median linezolid trough concentrations on day 3 were significantly higher in patients with renal impairment (creatinine clearance <60 mL/min) than in patients without renal impairment (14.7 versus 4.8 mg/L; P < 0.0001). Median linezolid trough concentrations on day 3 in patients who developed thrombocytopenia were also significantly higher than those in patients who did not (13.4 versus 4.3 mg/L, P < 0.0001). Development of thrombocytopenia occurred significantly more frequently in patients with linezolid trough concentration >7.5 mg/L (OR, 90.0; P < 0.0001) and renal impairment (OR, 39.0; P = 0.0002). The Kaplan-Meier plot showed that the median time from the initiation of therapy to development of thrombocytopenia was 11 days. CONCLUSIONS: Patients with renal impairment are more likely to have a high plasma linezolid concentration. In addition, a high plasma linezolid concentration and renal impairment significantly affected the development of linezolid-induced thrombocytopenia. Further studies are required to evaluate whether therapeutic drug monitoring-guided dosage adjustment of linezolid decreases the adverse effects while maintaining treatment efficacy in patients with renal dysfunction.

Establishment of a normal reference value for serum ß2 microglobulin in Japanese children: reevaluation of its clinical usefulness.

OBJECTIVE: Serum ß2 microglobulin (ß2MG) is considered to be a marker of renal function, which is independently associated with age. However, only a few studies have reported the reference values for ß2MG in children thus far, particularly in young children. In this study, we evaluated the distribution of serum ß2MG values in healthy Japanese children and assessed its clinical usefulness. METHOD: The normal reference value of serum ß2MG was assessed in serum samples from 1131 normal Japanese children (504 boys and 627 girls; age 0-17 years). To test the validity of the reference value, serum samples from children with various kidney diseases were also examined retrospectively. RESULTS: The mean values for ß2MG were significantly negatively correlated with age (r = -0.47, P < 0.001). No significant difference was observed between the values of boys and girls in any age group. The established ß2MG reference range covered 99.7 % of patients with decreased kidney function below 75 % based on their serum creatinine (Cr) value and body length. CONCLUSION: The newly established ß2MG reference value in children can be used to detect kidney impairment in children. Serum ß2MG in combination with serum Cr used as markers for predicting glomerular function can provide an accurate detection of kidney dysfunction in children.

Reference ranges for serum cystatin C measurements in Japanese children by using 4 automated assays.

OBJECTIVE: The data available on reference ranges for cystatin C in children are limited, and there are discrepancies among the available data. The aim of this study was to describe the reference ranges for cystatin C in Japanese children by using 4 automated assays. METHODS: Serum cystatin C levels were measured in 1128 Japanese children aged 3 month to 16 years without kidney disease. We calculated age-, gender-, race- and assay-specific cystatin C ranges. RESULTS: For all 4 assays, the median serum cystatin C levels were raised in term infants compared with older children and decreased by the first 2 years. The median serum cystatin C levels remained constant throughout up to the age of 14 years and decreased in children aged 15-16 years. The median serum cystatin C levels in children aged 12-16 years were slightly higher in males than in females. Assay-specific differences were also observed in the levels of serum cystatin C measured. CONCLUSION: Age-, gender-, race- and assay-specific ranges for serum cystatin C should be used as another tool to assess kidney function in children.

Henoch-Schönlein purpura nephritis with nephrotic state in children: predictors of poor outcomes.

Nephritis develops in 18-81% of Henoch-Schönlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Schönlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4 years. The median follow-up period was 6.2 years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3 months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16-348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.

Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children: a multicenter study.

BACKGROUND: Enzymatic methods have recently been used to measure creatinine (Cr) instead of the Jaffe method. Therefore, it is necessary to determine the reference serum Cr value for these enzymatic methods to evaluate renal function in Japanese children. METHODS: To determine reference values of serum Cr in Japanese children, 1151 children (517 male, 634 female) aged between 1 month and 18 years had their serum Cr values measured by an enzymatic method. To be included in the study the children had to be without kidney disease, urogenital disease, infectious disease, inflammatory disease, dehydration, muscular disease, anomaly syndrome, cardiovascular disease, malignant disease, hypertension, liver or pancreas disease, or pregnancy. RESULTS: The medians of reference values increased gradually with age, i.e., 0.30 mg/dl at 4 years old and 0.41 mg/dl at 10 years old. In adolescence, they increased significantly more rapidly in males than in females. We found a linear regression equation capable of estimating the reference value of serum Cr in children aged 2-11 years, and quintic regression equations capable of estimating the reference values of serum Cr in male and female children of all ages. CONCLUSION: The reference serum Cr levels determined by an enzymatic method related to age, gender, and body length, and our linear and polynomial equations showing the relationship between body length and serum Cr level will be applicable for screening of renal function in Asian as well as Japanese children.

Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome.

BACKGROUND: We previously established a treatment protocol for conventional cyclosporine (Sandimmune, Novartis, Basel, Switzerland) in children with frequently relapsing nephrotic syndrome; ∼50% of patients remained relapse free for 2 years, without serious adverse events. Recently, microemulsified cyclosporine (Neoral, Novartis), which has a more stable absorption profile than conventional cyclosporine, has been developed. We tested the hypothesis that microemulsified cyclosporine is at least as effective as conventional cyclosporine. METHODS: To evaluate the safety and efficacy of microemulsified cyclosporine, a prospective, multicentre trial was conducted according to the previously established protocol, using microemulsified cyclosporine instead of conventional cyclosporine. The duration of treatment was 24 months. During the first 6 months, patients received microemulsified cyclosporine in a dose that maintained the trough level between 80 and 100 ng/mL of cyclosporine. For the next 18 months, the dose was adjusted to maintain a level between 60 and 80 ng/mL. RESULTS: A total of 62 patients (median age, 5.4 years; 48 males, 14 females) were studied. The frequency of relapse decreased from 4.6 ± 1.4 to 0.7 ± 1.5 times per year (P < 0.0001). The probability of relapse-free survival at Month 24 was 58.1% (95% confidence interval, 45.8-70.3%). The probability of progression (to frequently relapsing nephrotic syndrome)-free survival at Month 24 was 88.5% (95% confidence interval, 80.4-96.5%). Cyclosporine nephrotoxicity was detected in only 8.6% of patients who underwent renal biopsy after 2 years of treatment. Antihypertensive agents were administered to 12.9% of the patients to control hypertension without severe sequelae. CONCLUSIONS: Microemulsified cyclosporine administered according to our treatment protocol is safe and effective in children with frequently relapsing nephrotic syndrome.

Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome.

We conducted a prospective, multicenter trial to evaluate the efficacy and safety of a 12-month course of cyclosporine in children with steroid-resistant nephrotic syndrome (SRNS). Thirty-five patients were enrolled, of whom 28 had minimal change or diffuse mesangial proliferation (MC/DMP), and seven had focal segmental glomerulosclerosis (FSGS). All patients received cyclosporine and prednisolone; patients with FSGS additionally received methylprednisolone pulse therapy (MPT). The dose of cyclosporine was adjusted to maintain a trough level of 120-150 ng/ml during the initial 3 months of treatment, followed by 80-100 ng/ml during months 4-12. The primary end point was the remission rate at month 12. Remission was achieved in 23 of 28 (82.1%) patients in the MC/DMP group and in six of the seven (85.7%) patients in the FSGS group. Follow-up renal biopsies were performed in 26 patients (nine at month 12, 17 at month 24), and cyclosporine-related nephrotoxicity was detected in one (3.8%). Major adverse events comprised severe bacterial infections (two patients) and posterior reversible encephalopathy syndrome (one patient). In conclusion, a high remission rate was achieved in our patient cohort using a combined cyclosporine/ prednisolone treatment regimen in children with SRNS who had MC/DMP and a combined cyclosporine/prednisolone plus MPT regimen in children who had FSGS.

Typical MPGN with few urinary abnormalities.

We describe the concurrent appearance of membranoproliferative glomerulonephritis (MPGN) in renal biopsy samples and normal urinary sediment without hematuria, proteinuria, or renal dysfunction in 1 child and asymptomatic microscopic hematuria without significant proteinuria or renal dysfunction in 2 children who were subsequently followed up for many years. The only other abnormality detected was hypocomplementemia. This is the first report of biopsy-proven typical MPGN in patients with few urinary abnormalities. A renal biopsy should be considered in children with hypocomplementemia, regardless of urinalysis findings, to exclude MPGN.

[Peritoneal dialysis catheter-related complications].

UNLABELLED: The introduction of a double-cuff swan neck type catheter has reduced the frequency of peritonitis. The frequency of complications associated with insertion of this catheter has remained unknown. We evaluated these complications in patients aged < 20 years at the start of the chronic peritoneal dialysis using double-cuff swan neck catheters. SUBJECTS AND METHODS: The data from 221 double-cuff swan neck catheters of 126 patients inserted in our hospital between 1990 and 2001 were compared with 102 single-cuff straight catheters of 54 patients between 1982 and 1990. The frequency of catheter-related complications, such as dislocation, leakage with in/outflow malfunction and infection(exit-site/tunnel infection and peritonitis within a month after catheter insertion) were estimated. RESULTS: We observed 37 dislocations(17%), 37 leakages(17%) and 36 infections(16%) of all double-cuff swan neck catheters. Twenty-nine catheters were removed due to catheter-related complications: 18 dislocations(8%), 2 leakages(1%) and 9 infections(4%). Catheter removal due to dislocation occurred significantly more frequently in 12% of children who were > or = 6 years old than in 1% of children < 6 years old(p = 0.002). Eighty-three percent of dislocations could be returned by the whiplash method(alpha-replacer, JMS, Tokyo). Of all single-cuff straight catheters, 10 catheters were removed due to catheter-related complications: 4 dislocations(4%), 6 leakages(6%) and 12 infections(12%). CONCLUSION: A single-cuff straight type catheter was more frequently replaced because of leakage and infection than a double-cuff swan neck type catheter. A double-cuff swan neck catheter was more frequently replaced because of dislocation than a single-cuff straight catheter. When a double-cuff swan neck catheter is inserted particularly in older children, care should be taken to avoid dislocation.

Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial.

BACKGROUND AND OBJECTIVES: An open-label, multicenter, randomized phase II trial was conducted from July 1, 2005 to March 29, 2011 to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600-700 ng/ml for the first 6 months and 450-550 ng/ml for the next 18 months; for group B, it was set to 450-550 ng/ml for the first 6 months and 300-400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment. RESULTS: Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups. CONCLUSION: The sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved progression-free survival and reduced the relapse rate.

Two-year follow-up of a prospective clinical trial of cyclosporine for frequently relapsing nephrotic syndrome in children.

BACKGROUND AND OBJECTIVES: Although the safety and efficacy of cyclosporine in children with frequently relapsing nephrotic syndrome (FRNS) have been confirmed, no prospective follow-up data on relapse after cyclosporine have appeared. This study is a prospective follow-up trial after 2-year treatment with cyclosporine to investigate cyclosporine dependency after its discontinuation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants who had undergone 2-year protocol treatment with microemulsified cyclosporine for FRNS between January 2000 and December 2005 were followed for an additional 2 years. The primary end point was relapse-free survival after the complete discontinuation of cyclosporine, and the secondary end point was regression-free survival (time to regression to FRNS). RESULTS: After exclusion of 7 patients who showed regression to FRNS during the 2-year treatment period, 49 children (median age, 6.5 years) were followed, and classified as children without (n=32; group A) and with (n=17; group B) relapse during the initial cyclosporine treatment. Overall, relapse-free survival probability at 24 months after cyclosporine discontinuation was 15.3% and regression to FRNS-free survival probability was 40.8%. By group, the probability of relapse-free survival was significantly higher in group A (17.9%) than in group B (8.3%) (P<0.001). CONCLUSIONS: Children with FRNS who receive cyclosporine are at high risk of relapse after discontinuation, particularly those who experience relapse during cyclosporine treatment.

Unadjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected adults.

We evaluated the immune response to a 2009 influenza A (H1N1) unadjuvanted vaccine in HIV-infected patients and assessed the boosting effect of a second dose. HIV-infected adults were enrolled and scheduled to receive the H1N1 unadjuvanted vaccine containing 15µg of A/California/7/2009 haemagglutinin. Anti-H1N1 antibody titers were measured at enrollment and 4-8 weeks after each vaccination by using haemagglutination inhibition (HI) and virus neutralization (NT) assays. One hundred and four patients were analyzed. Seroconversion, as measured by using HI and NT assays, was observed in 52 (50.0%) patients and 49 (47.1%) patients, respectively, after the first dose. Seroconversion rate evaluated by using NT, but not HI, antibody titers was associated with HIV RNA levels of <400copies/ml (odds ratio, 3.21; 95% CI, 1.15-8.96). Other parameters, including CD4 cell count, were not associated with seroconversion. In a cohort that received two vaccine doses at a 4-8-week interval (n=54), the seroconversion rate and geometric mean titer for HI antibodies were 44.4% (95% CI, 30.8-58.1%) and 30.5 (95% CI, 19.9-46.9) after the first dose, respectively, and 48.1% (95% CI, 34.4-61.9%) and 39.0 (95% CI, 26.1-58.2) after the second dose, respectively. Among HIV-infected patients, the seroconversion rate was around 50% after the first dose of unadjuvanted vaccine. A second dose of vaccine had a limited boosting effect on immunity in this patient cohort.

Improved renal survival in Japanese children with IgA nephropathy.

Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976-1989 and 1990-2004. Actuarial survivals were calculated by Kaplan-Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990-2004 period was significantly better than that in 1976-1989 (p=0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p=0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N.

Segmental membranous glomerulonephritis in children: comparison with global membranous glomerulonephritis.

Generally, idiopathic membranous glomerulonephritis (MGN) is a global glomerular disease that affects the whole of the glomerulus. However, idiopathic segmental MGN (SMGN) that shows IgG deposits in a portion of the glomerulus is encountered often. For clarification of whether SMGN is the same entity as idiopathic global MGN (GMGN), the two diseases were compared. From 1978 to 2004, 38 children (11 with SMGN and 27 with GMGN) received a diagnosis of idiopathic MGN. Immunofluorescence microscopy showed segmental granular IgG staining along the capillary loops in SMGN, whereas GMGN showed global staining. On light microscopy, SMGN showed segmental thickening of the glomerular basement membrane, with spike formation, whereas GMGN showed global lesions. The frequency of C1q deposits in SMGN was significantly higher than that in GMGN (91 versus 41%; P < 0.01). On electron microscopy, mesangial electron-dense deposits were detected in 10 (91%) cases of SMGN and also were found in the subepithelial and intramembranous area, whereas only six (22%) cases of GMGN had mesangial electron-dense deposits (P < 0.001). There were no significant differences in clinical features between the groups. Two children with SMGN underwent a repeat biopsy 3 yr after the first biopsy, and both patients again showed SMGN. At the final observation (mean observation time 7.5 yr in SMGN and 12.4 yr in GMGN), all children of both groups had a good outcome. In conclusion, these findings as a whole suggest that SMGN may be another glomerular disease entity with child predominance that is distinctive from GMGN.

Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome (CNS) causes significant renal failure, and is classified into two types: (1) Finnish type; and (2) other, including diffuse mesangial sclerosis. Mutations of NPHS1 and NPHS2, which encode the slit diaphragm components nephrin and podocin, cause CNS and autosomal-recessive familial steroid-resistant nephrotic syndrome, respectively. Most patients with Finnish-type CNS in Europe and the United States have NPHS1 mutations. However, NPHS2 mutations have been detected in some cases. Mutations in ACTN4, encoding alpha-actinin-4, cause an autosomal-dominant focal segmental glomerulosclerosis. alpha-actinin-4 stabilizes the podocyte cytoskeleton structure, connecting with actin filaments. WT1 mutations, causing Wilm's tumor, have been demonstrated in some CNS patients with diffuse mesangial sclerosis. Systematic investigation of genes for CNS in Japan has never been performed. METHODS: To clarify the role of mutations in these four genes, we used polymerase chain reaction (PCR) and direct sequencing to investigate all exons and exon-intron boundaries for these genes in 13 unrelated CNS patients from regional pediatric kidney disease centers in Japan. RESULTS: A novel homozygous nonsense mutation of NPHS1, E246X in exon 7, and a novel homozygous deletion mutation of NPHS1, 2156_2163del in exon 16 were detected in one patient each. A novel homozygous nonsense mutation of NPHS2, R196X in exon 5, was found in one patient, and the same heterozygous nonsense mutation was detected in another. No ACTN4 or WT1 mutations were detected. CONCLUSION: These studies demonstrate that mutation of NPHS1 is not a major cause of CNS in Japanese patients, and that mutation of NPHS2 can be responsible for CNS in this population.

Evaluation of the inferior vena cava in potential pediatric renal transplant recipients.

Vascular anomalies due to occlusion or thrombosis of the inferior vena cava (IVC) may be hazardous to renal transplantation, and preoperative vascular evaluation is important for safe and successful surgery. The purpose of this study was to assess the utility and accuracy of two-dimensional time-of-flight (2D-TOF) magnetic resonance venography (MRV) as an alternative to conventional angiography for evaluating the IVC and iliac vein in potential pediatric renal transplant recipients. Four children with chronic renal failure were evaluated with 2D-TOF MRV by superior presaturation pulse and target maximum intensity projection. The whole MRV examination and filming required less than 30 min. All four patients had a normal IVC and iliac vein. Two of the patients underwent renal transplantation, and the MRV findings were in total agreement with the final anatomy revealed intraoperatively. MRV is accurate for evaluating the condition of the IVC and iliac vein. It is a reliable, noninvasive and rapid technique that can be considered as an alternative to invasive angiography for evaluation of children scheduled for transplantation. We recommend the use of this noninvasive procedure to ascertain the patency of the IVC in all infants and children with a history of indwelling catheters in the IVC or those with a propensity to thrombosis, i.e., all recipients with nephrotic syndrome. The insertion of catheters in the femoral vein in children who may become candidates for renal transplantation should be discouraged.

A-20C angiotensinogen gene polymorphism and proteinuria in childhood IgA nephropathy.

We have previously reported that the TT genotype of the angiotensinogen gene and the ID/DD genotype of the angiotensin-converting enzyme gene are associated with increased severity of proteinuria in IgA nephropathy in Japanese children. Recently it was reported that polymorphism at -20 from adenine to cytosine in the angiotensinogen gene, increasing the level of this transcript, was associated with the progression of renal dysfunction in adult IgA nephropathy. We therefore investigated whether this polymorphism is involved in IgA nephropathy in Japanese children. We identified this polymorphism in 105 children with IgA nephropathy and 119 healthy adults using polymerase chain reaction/restriction fragment length polymorphism analysis. At the time of biopsy, all patients had normal blood pressure and renal function. There were no differences in the genotypes and allele frequencies of this polymorphism between patients with IgA nephropathy and controls. The number of patients with the AC/CC genotype showing heavy proteinuria (>or=1.0 g/day per m(2) body surface area) at biopsy was significantly higher than that with the AA genotype ( P=0.039, chi-squared test). The AC/CC genotype of this polymorphism may be associated with an increased severity of proteinuria, suggesting that this polymorphism may play a significant role in the progression of IgA nephropathy in Japanese children.