Sequential maintenance therapy with cyclosporin A and mycophenolate mofetil for sustained remission of childhood steroid-resistant nephrotic syndrome

Nephrol Dial Transplant. 2012 May;27(5):1970-8. doi: 10.1093/ndt/gfr572. Epub 2011 Oct 4.

Abstract

Background: There is currently no established standard for maintenance therapy of steroid-resistant nephrotic syndrome (SRNS). We report the long-term clinical course, medication, pharmacokinetic data, and renal function of 23 children with primary, non-familial SRNS with focal segmental glomerulosclerosis (FSGS).

Methods: To achieve initial remission, patients were treated with high-dose intravenous (i. v.) methylprednisolone and oral cyclosporin A (CsA). Maintenance therapy included transient alternate day oral prednisolone, CsA and angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers. In 18 patients, mycophenolate mofetil (MMF) (adjusted to achieve blood mycophenolic acid trough concentrations > 2 μg/mL) was sequentially added, and 16 patients were converted to MMF monotherapy.

Results: During a mean follow-up time of 7.0 years (1.7-16.5 years; cumulative observation time 161 patient-years), sustained remission could be achieved in all patients. Five of 23 patients (21%) experienced 10 relapses; all responded to relapse therapy. Maintenance therapy could be permanently discontinued in seven patients (30%). After conversion from CsA to MMF, renal function improved significantly; the eGFR at last follow-up was 137 (range 106-198) mL/min × 1.73 m(2). The mean number of anti-hypertensive drugs decreased from 1.86 per patient after initial remission to 0.57 on MMF monotherapy (P < 0.002).

Conclusions: The data of this uncontrolled retrospective study indicate that in children with SRNS/FSGS achieving initial remission, a sequential steroid-free therapy consisting of a combination of CsA and MMF followed by MMF alone (with the addition of ACE inhibitors and angiotensin receptor blockers), can provide sustained long-term remission, preservation of renal function and better control of blood pressure.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Blood Pressure / drug effects
  • Child
  • Child, Preschool
  • Comorbidity
  • Cyclosporine / administration & dosage*
  • Cyclosporine / therapeutic use*
  • Drug Administration Schedule
  • Drug Resistance*
  • Female
  • Follow-Up Studies
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / epidemiology
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Injections, Intravenous
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / epidemiology
  • Prednisolone / therapeutic use
  • Remission Induction
  • Retrospective Studies
  • Steroids / therapeutic use*
  • Treatment Outcome

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Immunosuppressive Agents
  • Steroids
  • Cyclosporine
  • Prednisolone
  • Mycophenolic Acid