Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome

Kidney Int. 2012 Nov;82(10):1130-5. doi: 10.1038/ki.2012.238. Epub 2012 Jul 4.


There are limited data on the relative efficacy and safety of calcineurin inhibitors and alkylating agents for idiopathic steroid-resistant nephrotic syndrome in children. To clarify this, we compared tacrolimus and intravenous cyclophosphamide therapy in a multicenter, randomized, controlled trial of 131 consecutive pediatric patients with minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis, stratified for initial or late steroid resistance. Patients were randomized to receive tacrolimus for 12 months or 6-monthly infusions of intravenous cyclophosphamide with both arms receiving equal amounts of alternate-day prednisolone. The primary outcome of complete or partial remission at 6 months, based on spot urine protein to creatinine ratios, was significantly higher in children receiving tacrolimus compared to cyclophosphamide (hazard ratio 2.64). Complete remission was significantly higher with tacrolimus (52.4%) than with cyclophosphamide (14.8%). The secondary outcome of sustained remission or steroid-sensitive relapse of nephrotic syndrome at 12 months was significantly higher with tacrolimus than cyclophosphamide. Treatment withdrawal was higher with cyclophosphamide, chiefly due to systemic infections. Compared to cyclophosphamide, 3 patients required treatment with tacrolimus to achieve 1 additional remission. Thus, tacrolimus and prednisolone are effective, safe, and preferable to cyclophosphamide as the initial therapy for patients with steroid-resistant nephrotic syndrome.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • India
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Nephrotic Syndrome / complications
  • Nephrotic Syndrome / congenital*
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / drug therapy
  • Odds Ratio
  • Prednisolone / adverse effects
  • Prednisolone / therapeutic use*
  • Proportional Hazards Models
  • Prospective Studies
  • Proteinuria / drug therapy
  • Proteinuria / etiology
  • Recurrence
  • Remission Induction
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Immunosuppressive Agents
  • Cyclophosphamide
  • Prednisolone
  • Tacrolimus

Supplementary concepts

  • Nephrotic syndrome, idiopathic, steroid-resistant