Tacrolimus for Steroid-Resistant Nephrotic Syndrome in Children

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For children with nephrotic syndrome that does not respond to steroids, the combination of tacrolimus and prednisolone is preferable to cyclophosphamide, concludes a trial in Kidney International.

The randomized trial included 131 consecutive children with idiopathic steroid-resistant nephrotic syndrome at five pediatric nephrology units. Diagnoses included minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis. Patients were stratified for initial or late steroid resistance. They were then assigned to tacrolimus, 0.1 to 0.15 mg/kg/day for 12 months; or cyclophosphamide. The two groups received equal doses of alternate-day prednisolone.

Defined according to spot urine protein-to-creatinine ratios, the rate of complete or partial remission at 6 months was 82.5 percent with tacrolimus versus 45.9 percent with cyclophosphamide: hazard ratio 2.64. Complete remission rates were 52.4 percent versus 14.8 percent, respectively. The tacrolimus group also had a higher 12-month rate of sustained remission or steroid-sensitive relapse.

More children withdrew in the cyclophosphamide group, mainly because of infections. To achieve one additional remission, the number needed to treat with tacrolimus was three.

There is no agreed-upon approach to the management of idiopathic steroid-resistant nephrotic syndrome in children. This multicenter trial strongly supports the combination of tacrolimus and prednisolone over cyclophosphamide. The authors note that tacrolimus may cause acute nephrotoxicity, but this usually responds to dose reduction [Gulati A, et al: Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome. Kidney Int 2012: 82; 1130–1135].

January 2013 (Vol. 5, Number 1)