To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P[4.94E-20, odds ratio (OR) [1.90)

Our study found that 9.9 cases of pediatric IgA nephropathy were diagnosed per 100,000 in the pediatric population, which is equivalent to or slightly more than past reports. IgA nephropathy, which poses a high histologic risk, presents with heavy proteinuria; but the proteinuria remission rate following steroid therapy is high 3 years after treatment, which suggests that administration of steroids results in an improved clinical outcome.

Rituximab (RTX) is increasingly used for the treatment of refractory nephrotic syndrome due to its inhibitory effect on B cells which extends the period of remission, while lowering the dose of steroids needed for disease management. However, RTX can lead to various side effects, including Crohn's disease. Herein, we describe a case of a 15-year-old boy with refractory nephrotic syndrome diagnosed at age 9 years who developed Crohn's disease following RTX treatment. RTX was initiated in this patient at the age of 13 years 6 months due to occurrence of 12 relapses of nephrotic syndrome over a 4-year period, despite treatment using cyclosporine, steroid pulse therapy, and mycophenolate mofetil. The patient received 4 doses of RTX over a 2-year period (dose, 375 mg/m 2). Although the treatment was effective in extending the disease-free duration up to 6 months, at the age of 15 years 9 months, the patient developed abdominal pain, associated with frequent watery stools and rapid weight loss. Based on clinical and endoscopic findings, he was diagnosed with Crohn's disease and treated using infliximab. Remission of Crohn's disease was achieved with this treatment, with no further relapse of nephrotic syndrome. Infliximab is thought to extend the remission period of nephrotic syndrome. In this case, we propose that Crohn's disease was caused by an abnormal immune tolerance, secondary to the use of RTX, although the exact underlying mechanism remains to be clarified. Therefore, inflammatory bowel disease should be considered if severe abdominal symptoms with weight loss following RTX administration are observed.

Minimal change nephrotic syndrome (MCNS) is the major type of idiopathic nephrotic syndrome in children. Glucocorticoids and immunosuppressive agents are used for the treatment of MCNS. Although proteinuria resolves with glucocorticoids therapy in 90% of patients, the disease relapses in about 70% of them with the recurrence of proteinuria. Therefore, some children with MCNS need long−term glucocorticoid therapy. Growth failure is common during long−term treatment with glucocorticoids, although the cause of this complication is unknown. Since long− term glucocorticoid therapy is often required to treat nephrotic syndrome, growth retardation occurs in some patients. The growth of 75 patients with steroid−dependent nephrotic syndrome treated at our institution was evaluated. In6patients with growth retardation, serum levels of growth hormone and insulin−like growth factor were measured. Growth hormone deficiency was detected in 5 of them, and they were diagnosed as having glucocorticoid−induced growth failure. Recombinant growth hormone (GH) was administered to 4 of these 5 patients. Case 1 : A 9−year−old girl, who had developed nephrotic syndrome at the age of 2 years, with a height of 118.0 cm (−2.30 SD) was treated with GH for 6 years, and her height increased to 152.4 cm (−1.10 SD). Case 2 : A 14−year−old boy, who had developed nephrotic syndrome at the age of 3 years, with a height of 144.2 cm (−3.17 SD) was treated with GH for 3 years, and his height improved to 168.6 cm (−0.38 SD). Case 3 : A 15−year−old boy, who had developed nephrotic syndrome at the age of 5 years, with a height of 144.4 cm (−3.67 SD) was treated with GH for 26 months, and his height increased to 170.3 cm (−0.05 SD). Case 4 : An 11−year−old boy, who had developed nephrotic syndrome at the age of 3 years, with a height of 124.3 cm (−2.83 SD) was treated with GH for 66 months, and his height improved to 163.6 cm (−1.16 SD). Thus, all patients showed an increase of growth and reached the target range. The mean duration of glucocorticoid therapy before diagnosis of glucocorticoid−induced growth failure was,107,months and all patients displayed GH deficiency. This implies that GH deficiency is the cause of glucocorticoid−induced growth failure and we suggest that GH therapy is effective for the treatment of growth retardation.

Membranous Nephropathy (MN) is classified as idiopathic or secondary, with the known causes of secondary MN including the following : infections, autoimmune diseases, drug reactions and malignancies. Idiopathic membranous nephropathy (IMN) is more frequently than secondary in Japanese children. We retrospectively reviewed 27 children (20 boys, 7 girls) with membranous nephropathy in our hospital for the period of 1985 to 2005, aged 8.1 +−3.9 years at onset. 17 patients are idiopathic membranous Nephropathy (IMN), 10 patients are hepatitis B virus related membranous nephropathy (HBMN) that is the most causes of secondary MN. In result, urinary abnormalities were detected in 16 patients through school urinary screening, and in other 11 children through chance urinary abnormalities. Six patients had nephrotic syndrome at onset. Electron microscopic staging according to the classification by Ehrenreich and Churg was performed in all patients. IMN consists of stage in 4, in 9, and III in 4, while HBMN consist of stage I in 3, II in 6, and III in 4. Oral corticosteroid was given to 17 patients, immunosuppressive therapy with cyclosporin was administered to only one patients. In spite of treatment with corticosteroid or not, almost IMN patients showed complete remission of proteinuria at the follow-up of 10 years, and only one patient had isolated mild hematuria. From these results, we suggest that IMN and HBMN in Japanese children might take a better course and outcome than IMN in adults and non-Japanese children.