Genetic mutations and response to immunosuppressive therapy in paediatric steroid-resistant nephrotic syndrome
Keywords:
nephrotic syndrome, rituximab, mutations, genes, podocytes, kidneysAbstract
Introduction: The prevalence of congenital nephrotic syndrome, affecting approximately 1 in 6,000 newborns, underscores the relevance of this study. This research involved 15 children with steroid-resistant nephrotic syndrome (SRNS), 9 of whom underwent nephrobiopsy.
Objective: To evaluate the genetic conditionality of SRNS and the prognostic significance of immunosuppressive therapy.
Methods: A prospective observational study was conducted among 15 paediatric SRNS patients (1-14 years). Diagnosis was confirmed after four weeks of ineffective prednisone therapy (2 mg/kg/day). Venous blood samples (2-4 mL) were collected in EDTA tubes. Genomic DNA was extracted (QIAamp DNA Mini Kit, Qiagen) and analysed by PCR and Sanger sequencing for NPHS1, NPHS2, and WT1 mutations. One patient was diagnosed with Schimke immuno-osseous dysplasia due to a SMARCAL1 mutation; 9 children underwent ultrasound-guided renal biopsy. Non-responders to steroids received Cyclosporine A (5 mg/kg/day) or Rituximab (375 mg/m² i.v.). Fresolimumab (1-4 mg/kg i.v.) was evaluated for antifibrotic effects. Clinical monitoring included serum creatinine, eGFR, proteinuria, and albumin.
Results: Three children (8.6%) were found to have a genetic predisposition to nephrotic syndrome, with mutations in podocyte-related genes. Immunologically mediated nephrotic syndrome contributed to steroid resistance and recurrence after transplant. All patients initially received prednisone, with some switching to Cyclosporine A and Rituximab. Gene mutations, particularly in NPHS1, NPHS2, and WT1, are critical in understanding SRNS pathogenesis.
Conclusions: SRNS is primarily linked to recessive podocyte gene mutations. Genetic testing is essential for diagnosis and prognosis. Individualised long-term immunosuppressive therapy remains crucial to sustaining remission and preventing recurrence.
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