title: Sequential maintenance therapy with cyclosporin A and mycophenolate mofetil for sustained remission of childhood steroid-resistant nephrotic syndrome.
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.
authors: Department of Paediatric Nephrology, Charité Children’s Hospital, Berlin, Germany.
authors: Jutta
authors: J
authors: Gellermann
authors: Jochen H H
authors: JH
authors: Ehrich
authors: Uwe
authors: U
authors: Querfeld
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D011239:Prednisolone; D009173:Mycophenolic Acid