Depletion of clusterin in renal diseases causing nephrotic syndrome

Gian Marco Ghiggeri, Maurizio Bruschi, Giovanni Candiano, Maria Pia Rastaldi, Francesco Scolari, Patrizia Passerini, Luca Musante, Nicoletta Pertica, Gianluca Caridi, Franco Ferrario, Francesco Perfumo, Claudio Ponticelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2184-2194
Number of pages11
JournalKidney International
Volume62
Issue number6
DOIs
Publication statusPublished - 2002

Keywords

  • ApoJ
  • End-stage renal disease
  • Focal segmental glomerulosclerosis
  • Membranous nephropathy
  • Nephrotic syndrome
  • Proteinuria

ASJC Scopus subject areas

  • Nephrology

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