TY - JOUR
T1 - Depletion of clusterin in renal diseases causing nephrotic syndrome
AU - Ghiggeri, Gian Marco
AU - Bruschi, Maurizio
AU - Candiano, Giovanni
AU - Rastaldi, Maria Pia
AU - Scolari, Francesco
AU - Passerini, Patrizia
AU - Musante, Luca
AU - Pertica, Nicoletta
AU - Caridi, Gianluca
AU - Ferrario, Franco
AU - Perfumo, Francesco
AU - Ponticelli, Claudio
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - ApoJ
KW - End-stage renal disease
KW - Focal segmental glomerulosclerosis
KW - Membranous nephropathy
KW - Nephrotic syndrome
KW - Proteinuria
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U2 - 10.1046/j.1523-1755.2002.00664.x
DO - 10.1046/j.1523-1755.2002.00664.x
M3 - Article
C2 - 12427144
AN - SCOPUS:18744406280
VL - 62
SP - 2184
EP - 2194
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 6
ER -