Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children.

BACKGROUND AND OBJECTIVES: Frequently relapsing and steroid-dependent minimal-change nephrotic syndrome (MCNS) that originates in childhood can persist after puberty in >20% of patients. These patients require immunosuppressive treatment during several decades of their life. We examined long-term adverse effects of persistent nephrotic syndrome and immunosuppressive medications, focusing on renal function, growth, obesity, osteoporosis, hypertension, ocular complications, and fertility in adult patients with biopsy-proven childhood-onset MCNS. Molecular analysis was performed to evaluate a possible association of a complicated course of MCNS with podocyte gene mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a prospective clinical examination of 15 adult patients that included serum and urine analysis; dual-energy x-ray absorptiometry; ophthalmologic examination; semen examination; and molecular analysis of NPHS1, NPHS2, CD2AP, and ACTN4 genes. RESULTS: All patients had normal GFR. Most frequent long-term complications were hypertension (in seven of 15 patients) and osteoporosis in one third of patients. Oligozoospermia was found in one patient, reduced sperm motility in four of eight patients, and teratozoospermia in six of eight patients. Ophthalmologic examination revealed myopia in 10 of 15 patients and cataract in three of 15 patients. CONCLUSIONS: Children with MCNS that persists after puberty are at risk for complications such as osteoporosis, hypertension, cataract, and sperm abnormalities. Our study underscores a need for more effective and less toxic therapies for relapsing MCNS.

Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome.

BACKGROUND: Seventy percent of children with minimal change nephrotic syndrome (MCNS) have a steroid-dependent or frequent relapsing course of the disease, and most are treated with cyclophosphamide. We describe the clinical course of children with biopsy-proven MCNS treated with cyclophosphamide for steroid-dependent or frequently relapsing nephrotic syndrome at our institution from 1971 to 2003. METHODS: From our pathology registry, we identified 93 patients with biopsy-proven MCNS who received cyclophosphamide therapy. Follow-up information from medical records and mailed questionnaires could be obtained for 80 patients (86%). RESULTS: Only 35% of patients experienced no relapse after cyclophosphamide therapy. Twenty-one patients subsequently were treated with cyclosporine, with only 3 (14%) achieving persistent remission. At the end of follow-up, 23 patients (25%) still experienced relapse, and all except 3 patients required continuous immunosuppressive therapy. However, the cumulative incidence of persistent complete remission (>2 years without medication) increased over time (35% at 2 years, 52% at 6 years, and 71% at 15 years after the start of cyclophosphamide therapy), and no patient developed kidney failure. By means of univariate analysis, age younger than 3 years at onset predicted a lower likelihood of attaining remission (P < 0.05). CONCLUSION: More than a quarter of a selected group of cyclophosphamide-treated patients with steroid-dependent or frequently relapsing MCNS were not in remission after puberty and required prolonged immunosuppressive treatment. There is an urgent need for more effective treatment modalities resulting in persistent remission in these patients.