Urinary Clusterin in Chronic Nephrotoxicity in the Rat

Abstract

The excretion of clusterin was compared with that of N-acetyl-beta-glucosaminidase (NAG) in rats given gentamicin daily for 2 months to determine whether clusterin excretion stays elevated after NAG excretion falls during chronic gentamicin administration. Clusterin was measured by radioimmunoassay and NAG by the hydrolysis of 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide. Gentamicin at 110 mg/kg was given daily for 44 days and thereafter, at 90 mg/kg daily. The excretion rate of both proteins rose rapidly, peaked, and then declined; however, the clusterin values stayed significantly above control values for the entire study, whereas NAG values were close to normal during the last 10 days, even though tubulointerstitial disease was active at that time. For this reason, the further evaluation of clusterin as a marker of renal tubular cell injury or death is warranted.

Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries

“…In the kidney, clusterin is found prominently only in the early stages of nephron development (French et al 1993;Harding et al 1991), but it reappears after various types of acute and chronic injury (Buttyan et al 1989;Correa-Rotter et al 1992;Cowley and Rupp 1995;Harding et al 1991;Nath et al 1994;Obermüller et al 1997;Pearse et al 1992;Rosenberg and Paller 1991;Witzgall et al 1994). Since urinary excretion of clusterin increases after gentamicin-induced acute renal failure (Aulitzky et al 1992;Eti et al 1993), we have hypothesized that it could also be used as a valuable laboratory marker of renal ischemia-reperfusion damage. Furthermore, we have tested its use in a hereditary model of renal disease, i.e., the (cy/+) rat model of ADPKD, which slowly develops chronic renal failure.…”

Urinary clusterin concentrations - a possible marker of nephropathy? Pilot study

“…Several years ago, the potential importance of serum clusterin was written in the diagnosis of renal disorders; many patients with renal disorders had lower urinary clusterin, which was considered as one cause of renal diseases (e.g. clusterin defi ciency leads to activation of complement cascade and thus to possible renal injury) [5][6][7][8][9][10][11] . On the other hand, there is experimental evidence that individuals with impaired renal parenchyma or toxic injury have higher urinary clusterin concentrations (together with other proteins) 6,10,12 .…”

“…clusterin defi ciency leads to activation of complement cascade and thus to possible renal injury) [5][6][7][8][9][10][11] . On the other hand, there is experimental evidence that individuals with impaired renal parenchyma or toxic injury have higher urinary clusterin concentrations (together with other proteins) 6,10,12 . This is interesting apropos clusterin production by a stressed cell; enhanced urinary clusterin levels could be permanent and independent of diuresis changes or renal perfusion 4,6 .…”

Differential Expression of Plasma Proteins in Cyclosporine A-Induced Rat Acute Nephrotoxicity

“…27) Clusterin (CLUS), which was also newly induced in rats treated with high-dose CsA, is a heterodimeric glycoprotein induced after renal tubular cell injury. [30][31][32][33] Although there are a few reported studies on CsA nephrotoxicity inducing CLUS, 30) a great number of publications have reported the function of CLUS in the physiology and pathology of the kidney. [31][32][33][34] The basal expression of CLUS in the kidney is minimal and confined to rare distal tubular cells, but it is markedly induced in a variety of tubular injury states.…”

“…[30][31][32][33] Although there are a few reported studies on CsA nephrotoxicity inducing CLUS, 30) a great number of publications have reported the function of CLUS in the physiology and pathology of the kidney. [31][32][33][34] The basal expression of CLUS in the kidney is minimal and confined to rare distal tubular cells, but it is markedly induced in a variety of tubular injury states. 32) Numerous functions have been proposed for CLUS, including complement inhibition, lipid transport, apoptosis, membrane protection, and maintenance of normal cell interactions.…”