Relative safety of steroid sparing agents in frequently relapsing, steroid dependent and steroid resistant nephrotic syndrome in pediatric patients

Sabnam Ara Begum, Santanu Kumar Tripathi, Mousumi Nandy, Sanat Kumar Ghosh, Shatavisa Mukherjee, Debajyoti Saha


Background: In patients with frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) and steroid resistant nephrotic syndrome (SRNS) steroids are either used for prolonged period of time or ineffective. To reduce the degree of steroid dependency and avoid steroid toxicity, several immunosuppressive steroid sparing agents (SPAs) have been proposed to treat these children. The present study tried to study the relative safety of most commonly steroid sparing agent in such children.

Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.

Results: A total 110 patients were screened, examined and enrolled. Levamisole, cyclophosphamide and MMF were commonly used SPAs. Of the two tertiary care hospitals, all the patients of FRNS and SDNS were started with levamisole and SRNS with cyclophosphamide in one set-up, while in the other hospital some SDNS patients were started with cyclophosphamide and SRNS with MMF but without clinically significant outcomes. In comparison with few minor adverse events in MMF group, some serious adverse events were documented in the both cyclophosphamide and levamisole groups.

Conclusions: Levamisole being a very efficacious, safe and easily affordable drug, should be used as an initial first line SPA in treating FRNS and SDNS children. The side effect profiles of levamisole and MMF are much more patient friendly.


Frequently relapsing nephrotic syndrome, Safety, Steroid-dependent nephrotic syndrome, Steroid resistant nephrotic syndrome, Steroid sparing agents

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Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease Children. Kidney Int. 1978;13:159-65.

The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International study of kidney disease in children. J Pediatr. 1981;98(4):561-4.

Niaudet P. Steroid-sensitive idiopathic nephrotic syndrome. In: Avner ED, Harmon WE, Niaudet P, editors. Pediatric nephrology. 5th ed. Philadelphia: Lippincott Williams and Wilkins; 2004:545-573.

Schulman SL, Kaiser BA, Polinsky MS, Srinivasan R, Baluarte HJ. Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: superiority of response to corticosteroid therapy over histopathologic patterns. J Pediatr. 1988;113:996-1001.

Steroid-sensitive nephrotic syndrome in children. In: Avner ED, Harmon WE, Niaudet P, editors. Pediatric Nephrology. Philadelphia: Lippincott Williams and Wilkins; 2004:543-556.

Hodson EM, Craig JC, Willis NS. Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2005;20:1523-30.

The use of the WHO-UMC system for standardised case causality assessment. Available at: Accessed on 15th January 2020.

Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm. 1992;49(9):2229-32.

Neuhaus TJ, Fay J, Dillon MJ, Trompeter RS, Barratt TM. Alternative treatment to corticosteroids in steroid sensitive idiopathic nephrotic syndrome. Arch Dis Child. 1994;71:522-6.

Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Report of a workshop by the British Association for Paediatric Nephrology and Research Unit. Royal College of Physicians. Arch Dis Child. 1994;70:151-7.

Trompeter RS. Minimal change nephrotic syndrome and cyclophosphamide. Arch Dis Child. 1986;61:727-9.

Andreoli SP. Racial and ethnic differences in the incidence and progression of focal segmental glomerulosclerosis in children. Adv Renal Replace Ther. 2004;11:105-9.

Bagga A, Sharma A, Srivastata RN. Levamisole therapy in corticosteroid dependent nephrotic syndrome. Pediatr Nephrol. 1997;11:415-7.

Lombel RM, Gipson DS, Hodson EM. Kidney disease: improving global outcomes. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol. 2013;28:415-61.

Pravitsitthikul N, Willis NS, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2013;10:CD002290.

Barbano G, Ginevri F, Ghiggeri GM, Gusmano R. Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome. Pediatr Nephrol. 1999;13:602-3.

Bulugahapitiya DT. Liver toxicity in a nephrotic patient treated with levamisole. Arch Dis Child. 1997;76:289.

Palcoux JB, Niaudet P, Goumy P. Side effects of levamisole in children with nephrosis. Pediatr Nephrol. 1994;8:263-4.