Management of steroid-resistant nephrotic syndrome in children and adolescents
Kjell Tullus1, Hazel Webb1, Arvind Bagga2
1Nephrology Unit, Great Ormond Street Hospital for Children, Great Ormond Street, London, UK.
Insights
Most children with nephrotic syndrome respond to corticosteroids. Steroid-resistant nephrotic syndrome (SRNS) in children may involve genetic mutations or unknown factors, often treated with calcineurin inhibitors.
Area of Science:
- Pediatric Nephrology
- Genetics
- Immunology
Background:
- Idiopathic nephrotic syndrome (INS) affects children, with most responding to corticosteroid therapy.
- Steroid-resistant nephrotic syndrome (SRNS) is diagnosed when proteinuria persists after 4 weeks of daily prednisolone.
- Renal histology in SRNS often reveals focal segmental glomerulosclerosis (FSGS) or minimal change disease.
Purpose of the Study:
- To review the understanding and management of steroid-resistant nephrotic syndrome in children.
- To highlight the genetic underpinnings and potential etiological factors in SRNS.
- To discuss current and potential therapeutic strategies for SRNS.
Main Methods:
- Review of existing literature on idiopathic nephrotic syndrome and SRNS.
- Analysis of histological findings in SRNS patients.
- Evaluation of treatment outcomes for calcineurin inhibitors and other immunosuppressive therapies.
Main Results:
- Approximately one-third of SRNS cases are linked to mutations in podocyte genes.
- Calcineurin inhibitors (cyclosporine, tacrolimus) achieve remission in about 70% of non-genetic SRNS cases.
- Renin-angiotensin axis inhibitors are recommended for managing hypertension and proteinuria.
- Recurrent FSGS post-transplantation can occur, sometimes responding to plasma exchange, rituximab, and intensified immunosuppression.
Conclusions:
- SRNS management requires tailored approaches based on etiology (genetic vs. non-genetic).
- Calcineurin inhibitors are effective for non-genetic SRNS, but long-term outcomes and risks need consideration.
- Further research into the causes and treatments of SRNS is crucial, especially for refractory cases and post-transplant recurrence.
Abstract:
More than 85% of children and adolescents (majority between 1-12 years old) with idiopathic nephrotic syndrome show complete remission of proteinuria following daily treatment with corticosteroids. Patients who do not show remission after 4 weeks' treatment with daily prednisolone are considered to have steroid-resistant nephrotic syndrome (SRNS). Renal histology in most patients shows presence of focal segmental glomerulosclerosis, minimal change disease, and (rarely) mesangioproliferative glomerulonephritis. A third of patients with SRNS show mutations in one of the key podocyte genes. The remaining cases of SRNS are probably caused by an undefined circulating factor. Treatment with calcineurin inhibitors (ciclosporin and tacrolimus) is the standard of care for patients with non-genetic SRNS, and approximately 70% of patients achieve a complete or partial remission and show satisfactory long-term outcome. Additional treatment with drugs that inhibit the renin-angiotensin axis is recommended for hypertension and for reducing remaining proteinuria. Patients with SRNS who do not respond to treatment with calcineurin inhibitors or other immunosuppressive drugs can show declining kidney function and are at risk for end-stage renal failure. Approximately a third of those who undergo renal transplantation show recurrent focal segmental glomerulosclerosis in the allograft and often respond to combined treatment with plasma exchange, rituximab, and intensified immunosuppression.
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