Clinical Scenario:
An 8-year-old boy presents with generalized edema and heavy proteinuria. He was diagnosed with idiopathic nephrotic syndrome 6 weeks ago and has received prednisolone 2 mg/kg/day (maximum 60 mg/day) for 6 weeks with good compliance. Despite treatment, he continues to have 4+ proteinuria on urine dipstick, serum albumin is 1.8 g/dL, and urine protein/creatinine ratio is 9 mg/mg. His serum creatinine is normal, complement levels (C3 and C4) are normal, and there is no evidence of secondary causes of nephrotic syndrome. A renal biopsy reveals minimal change disease.
What is the most appropriate next-line treatment?
A. Cyclophosphamide
B. Cyclosporine
C. Mycophenolate mofetil
D. Rituximab
E. Tacrolimus
Correct Answer & Explanation:
Correct Answer : B
This child has steroid-resistant nephrotic syndrome (SRNS), defined as failure to achieve remission after 6 weeks of daily corticosteroid therapy. According to current KDIGO and IPNA recommendations, a calcineurin inhibitor (CNI) is the first-line immunosuppressive therapy for primary SRNS. Cyclosporine (or tacrolimus) is recommended together with low-dose corticosteroids.
Why the other options are incorrect
A. Cyclophosphamide: Effective mainly in frequently relapsing or steroid-dependent nephrotic syndrome; not recommended for SRNS.
C. Mycophenolate mofetil: Less effective than calcineurin inhibitors as initial therapy for SRNS.
D. Rituximab: Generally reserved for selected refractory cases or steroid-dependent/frequently relapsing disease, not first-line treatment for SRNS.
E. Tacrolimus: Also an acceptable first-line calcineurin inhibitor. However, if a single best answer is required, cyclosporine is the classic guideline-supported choice and has the strongest historical evidence.
Learning Point:
The cornerstone of treatment for primary steroid-resistant nephrotic syndrome is a calcineurin inhibitor (cyclosporine or tacrolimus) administered for at least 6 months while monitoring drug levels and renal function. Before initiating therapy, secondary causes should be excluded, and a kidney biopsy should be performed.
