title: Depletion of clusterin in renal diseases causing nephrotic syndrome.
abstract: BACKGROUND
  Clusterin is a lipoprotein that has anti-complement effects in membranous nephropathy (MN). In focal segmental glomerulosclerosis (FSGS), it inhibits permeability plasma factor activity and could influence proteinuria. Moreover, with aging, knockout mice for clusterin develop a progressive glomerulopathy with sclerosis.
  
  
  METHODS
  Since little is known about clusterin metabolism in humans, we determined clusterin levels and composition in the sera and urine of 23 patients with MN, 25 with FSGS and 23 with steroid-responsive nephrotic syndrome (NS). Renal localization was evaluated by immunofluorescence and morphometry.
  
  
  RESULTS
  Serum clusterin was markedly reduced in active MN, in FSGS and in children with NS compared to controls; after stable remission of proteinuria, nearly normal levels were restored. Among various biochemical variables, serum clusterin was inversely correlated with hypercholesterolemia. Urinary clusterin, representing a 0.01 fraction of serum, was higher in the urine from normal subjects and FSGS patients in remission with proteinuric MN, FSGS and idiopathic NS; clusterin was inversely correlated with proteinuria. In all cases, urinary and serum clusterin was composed of the same 80 kD isoforms. Finally, a decrease in focal segmental or global clusterin staining was found in FSGS glomeruli, especially in areas of sclerosis. Instead, in MN an overall increment of staining was observed that ranged from mild/focal to very intense/diffuse.
  
  
  CONCLUSIONS
  The overall pool of clusterin is reduced in glomerular diseases causing nephrotic syndrome, with hypercholesterolemia appearing as the unifying feature. Depletion of clusterin should negatively affect the clinical outcome in nephrotic patients and efforts should be aimed at normalizing clusterin overall pool.
authors.affiliation: Laboratory on Pathophysiology of Uremia and Unit of Nephrology, Istituto Giannina Gaslini, Genova, Italy. labnefro@ospedale-gaslini.ge.it
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Passerini
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pertica
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrario
authors.forename: Francesco
authors.initials: F
authors.lastname: Perfumo
authors.forename: Claudio
authors.initials: C
authors.lastname: Ponticelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051152:Clusterin; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000150:complications / Q000652:urine; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000150:complications / Q000652:urine; D006023:Glycoproteins / Q000097:blood* / Q000652:urine; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000097:blood* / Q000652:urine; D009404:Nephrotic Syndrome / Q000097:blood* / Q000209:etiology* / Q000652:urine
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones