Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations

Pediatr Nephrol. 2010 Jul;25(7):1285-9. doi: 10.1007/s00467-010-1468-3. Epub 2010 Feb 27.


The Wilms' tumor suppressor gene 1 (WT1) encodes a transcription factor involved in kidney and gonadal development. WT1 is also a key regulator of podocyte functions and mutations have been found in a small percentage of children with isolated or syndromal steroid-resistant nephrotic syndrome. It is commonly assumed that the nephrotic syndrome (NS) in patients with WT1 mutations is unresponsive to therapy and characterized by rapid progression to end-stage renal disease. We report long-term observations in 3 children with focal-segmental glomerulosclerosis associated with WT1 mutations and NS (2 cases) or nephrotic range proteinuria (1 case). All patients showed a favorable response to an intensified therapy consisting of cyclosporin A (CyA) in combination with induction therapy with intravenous and oral prednisone. Treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was added to the regimen at various times. As shown both by the short-term response and during long-term follow-up, this treatment resulted in clinical remission of the NS and/or significant reduction of proteinuria, while normal renal function could be maintained over many years. Thus, glomerular diseases in selected patients with mutations in genes regulating renal development and podocyte function may respond to combination therapy with CyA and corticosteroids.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Adolescent
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Child
  • Cyclosporine / therapeutic use*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / genetics
  • Humans
  • Injections, Intravenous
  • Male
  • Mutation*
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / metabolism
  • Prednisone / therapeutic use*
  • Proteinuria / drug therapy
  • Proteinuria / genetics
  • Treatment Outcome
  • WT1 Proteins / genetics*
  • WT1 Proteins / metabolism


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • WT1 Proteins
  • Cyclosporine
  • Prednisone