Renal handling of radiolabelled human cystatin C in the rat

Abstract

Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than that of serum creatinine, suggesting a constant formation, and elimination from extracellular fluid mainly by glomerular filtration. It is not known, however, how well the renal plasma clearance of this 13-kDa basic polypeptide matches the glomerular filtration rate. This was investigated in rats during control conditions and after reduced renal perfusion pressure. 125I-cystatin C and an indicator for glomerular filtration (51Cr-EDTA or 131I-aprotinin) were injected intravenously. The renal accumulation and urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The renal plasma clearance of 125I-cystatin C (Ccy) based on the renal content of 125I correlated well with the glomerular filtration rate (CCr-EDTA) in periods up to 6 min; i.e. Ccy = 0.94 x CCr-EDTA, r = 0.99. Less than 0.5% of the filtered amount appeared in the urine. During more prolonged periods, Ccy increasingly underestimated glomerular filtration rate, reaching about 0.4 x CCr-EDTA in a 20-min period. Free 125I relative to total plasma 125I activity increased from about 2% at 5 min to about 70% at 20 min. In nephrectomized rats, free 125I accumulated in plasma at a slower rate, accounting for about 15% of the total activity 20 min after injection of 125I-cystatin C. We conclude that cystatin C is (a) mainly removed from the extracellular fluid by the kidneys, (b) practically freely filtered in the glomeruli, and (c) completely absorbed and rapidly broken down by the proximal tubular cells.

Measured GFR as a Confirmatory Test for Estimated GFR

“…One of the limitations of cystatin C is that it is catabolized and reabsorbed by the tubules. 44,45 As such, its urinary clearance cannot be measured.…”

Cystatin C: current position and future prospects

“…After being filtered without restriction by the glomeruli because of its low molecular mass and absence of protein binding, CysC is entirely reabsorbed by the proximal tubules, where it is almost entirely catabolised (26,27,69). Tubular reabsorption occurs through a receptor, megalin (common to many proteins including albumin) by endocytosis (70)(71)(72).…”

“…There are relatively few specific physiological studies on CysC, the main one of which was conducted in the rat (69). After being filtered without restriction by the glomeruli because of its low molecular mass and absence of protein binding, CysC is entirely reabsorbed by the proximal tubules, where it is almost entirely catabolised (26,27,69).…”

Glomerular filtration rate measurement and estimation in chronic kidney disease

“…Blood cystatin C level is approximately 1 mg/l in healthy individuals [37]. Cystatin C is catabolized and almost completely reabsorbed by renal proximal tubular cells, so that little is excreted in the urine [38] and cannot be used to calculate a clearance GFR. Interindividual variation of cystatin C level is significantly less (25%) than that of creatinine (93%) [39].…”