Embryonal hyperplasia of Bowman's capsular epithelium in patients with WT1 mutations

Pediatr Nephrol. 2003 Jan;18(1):9-13. doi: 10.1007/s00467-002-1019-7. Epub 2002 Nov 22.

Abstract

Embryonal hyperplasia of Bowman's capsular epithelium (EHBCE) is a rare condition, observed in patients with end-stage renal disease when treated with long-term dialysis. Immunohistochemical studies have suggested that EHBCE originates from the visceral epithelium of the Bowman's capsule. Here we report two patients with WT1 missense mutations in exon 7, who received continuous ambulatory peritoneal dialysis and developed EHBCE without Wilms tumor. One patient showed manifestations of Denys-Drash syndrome (DDS), while the other patient exhibited rapid progress into end-stage renal disease, but no genitourinary anomaly. Recently, abnormal expression of WT1 and PAX2 was shown in the podocytes in diffuse mesangial sclerosis (DMS) associated with DDS and isolated DMS. We hypothesize that EHBCE is a reversion of Bowman's capsular epithelial cells to an earlier cell differentiation state, which has the characteristics of a progenitor cell of both Bowman's capsular epithelia and podocytes. Immunohistochemical analysis of WT1, PAX2, vimentin, cytokeratin, and epithelial membrane antigen was performed in the kidney specimens obtained at autopsy or surgery. Abnormal expression of WT1 and PAX2 in the EHBCE was observed in both patients, supporting our hypothesis. The nephropathy associated with constitutional WT1 mutations might therefore be associated with EHBCE.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Denys-Drash Syndrome / genetics
  • Denys-Drash Syndrome / physiopathology
  • Epithelium / metabolism
  • Epithelium / pathology
  • Female
  • Humans
  • Hyperplasia / etiology
  • Hyperplasia / genetics
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Infant
  • Kidney / cytology
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / pathology*
  • Male
  • Mutation
  • PAX2 Transcription Factor
  • Peritoneal Dialysis / adverse effects*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • WT1 Proteins / genetics*
  • WT1 Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • Transcription Factors
  • WT1 Proteins