title: Podocytopenia and disease severity in IgA nephropathy.
abstract: BACKGROUND
  IgA nephropathy is a common form of progressive glomerular disease, associated with proliferation of mesangial cells and mesangial deposition of IgA. The present study was designed to investigate functional and morphological covariates of disease severity in patients with IgA nephropathy.
  
  
  METHODS
  Glomerular hemodynamics, permselectivity and ultrastructure were studied in 17 adult patients with IgA nephropathy using inulin, para-aminohippuric acid (PAH) and 3H-Ficoll clearances and morphometric methods. A mathematical model of macromolecule permeation through a heteroporous membrane was used to characterize glomerular permselectivity. Controls consisted of 14 healthy living kidney donors and 12 healthy volunteers.
  
  
  RESULTS
  The patients were heterogeneous in their disease severity, but as a group had a decreased glomerular filtration rate (GFR) and increased urinary protein excretion compared to controls [63 +/- 29 SD vs. 104 +/- 23 mL/min/1.73 m2, P < 0.001, and (median) 1.34 vs. 0.11 g/day, P < 0.0001, respectively). A multivariate analysis of structural and functional relationships revealed GFR depression to be most strongly correlated with the prevalence of global glomerular sclerosis (t = -4.073, P = 0.002). Those patients with the most severe glomerular dysfunction had a reduced number of glomerular visceral epithelial cells (podocytes) per glomerulus. The degree of podocytopenia was related to the extent of glomerular sclerosis and of impairment of permselectivity and GFR, with worsening injury below an apparent threshold podocyte number of about 250 cells per glomerulus. There were no corresponding correlations between these indices of injury and the number of mesangial and endothelial cells.
  
  
  CONCLUSIONS
  Our findings show that podocyte loss is a concomitant of increasing disease severity in IgA nephropathy. This suggests that podocyte loss may either cause or contribute to the progressive proteinuria, glomerular sclerosis and filtration failure seen in this disorder.
authors.affiliation: Division of Pediatric Nephrology, Stanford University School of Medicine,Stanford, California 94305-5208, USA. klemley@stanford.edu
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Lemley
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lafayette
authors.forename: Massy
authors.initials: M
authors.lastname: Safai
authors.forename: Geraldine
authors.initials: G
authors.lastname: Derby
authors.forename: Kristina
authors.initials: K
authors.lastname: Blouch
authors.forename: Addy
authors.initials: A
authors.lastname: Squarer
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Myers
mesh_terms: D000328:Adult; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability; D002452:Cell Count; D004847:Epithelial Cells / Q000473:pathology; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000503:physiopathology* / Q000652:urine; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation; D019520:Living Donors; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology; D012016:Reference Values; D012720:Severity of Illness Index