Clinical Scenario:
A 9-year-old boy presents with generalized edema and frothy urine. He has heavy proteinuria, hypoalbuminemia and hyperlipidemia. His blood pressure is 132/88 mmHg. Urinalysis shows 3+ protein with microscopic hematuria.
He is treated with an adequate course of daily oral prednisolone, but remains nephrotic with persistent heavy proteinuria. Renal function is initially normal.
A renal biopsy shows focal and segmental areas of glomerular sclerosis with no immune-complex deposition.
Which of the following is the most appropriate treatment?
A. Continue prednisolone alone
B. Cyclophosphamide
C. Cyclosporine
D. Mycophenolate mofetil
E. Rituximab
Correct answer & Explanation:
Explanation
Correct answer: C. Cyclosporine
This child has steroid-resistant nephrotic syndrome (SRNS) with renal biopsy findings of focal segmental glomerulosclerosis (FSGS).
The clinical picture is suggestive of FSGS because he is an older child with nephrotic syndrome and has hypertension and microscopic hematuria, features that are less typical of uncomplicated minimal change disease. Most importantly, he has persistent heavy proteinuria despite an adequate course of glucocorticoid therapy, indicating steroid resistance.
Renal biopsy demonstrates focal and segmental glomerular sclerosis:
- Focal means that only some glomeruli are affected.
- Segmental means that only a portion of an affected glomerulus is sclerosed.
According to the KDIGO 2025 Clinical Practice Guideline, cyclosporine or tacrolimus, both calcineurin inhibitors, are recommended as initial second-line therapy for children with steroid-resistant nephrotic syndrome. Therefore, among the options given, cyclosporine is the best answer. Calcineurin inhibitor therapy should be monitored carefully because of potential nephrotoxicity.
Why not continue prednisolone alone?
Persistent nephrotic syndrome after an adequate steroid course indicates steroid resistance. Continuing prednisolone alone is unlikely to induce remission.
Why not cyclophosphamide?
Cyclophosphamide is not the preferred treatment for steroid-resistant nephrotic syndrome when calcineurin inhibitors are available. Current KDIGO guidance notes that randomized trials have not shown benefit for cyclophosphamide in SRNS.
Why not mycophenolate mofetil?
MMF is not the preferred initial second-line treatment for SRNS. It may have a role in selected situations, including maintaining remission after a stable response to a calcineurin inhibitor.
Why not rituximab?
Rituximab is generally considered in more resistant or selected cases and is not the standard initial second-line therapy for childhood SRNS.
Key point:
In a child with steroid-resistant nephrotic syndrome, especially when biopsy demonstrates FSGS, think of a calcineurin inhibitor—cyclosporine or tacrolimus—as the preferred next immunosuppressive treatment.
Reference:
Kidney Disease: Improving Global Outcomes (KDIGO) Nephrotic Syndrome in Children Work Group. KDIGO 2025 Clinical Practice Guideline for the Management of Nephrotic Syndrome in Children. Kidney International. 2025;107(5S):S241–S289. doi:10.1016/j.kint.2024.11.007.
