Cystatin functions

Serum creatinine is not a good measure of renal function in elderly because muscle mass is reduced and the production of creatinine is thus reduced. Estimation of GFR based on serum creatinine is therefore not accurate enough in the elderly (Baracskay et al. 1997). Creatinine clearance should be used instead. Another possibility is measurement of cystatin C in plasma. The rate of production of cystatin C is relatively constant so it seems to be a more reliable estimation of GFR also in older adults. 

His1 0 and orients it for its catalytic function [54], The putative catalytic thiolate-imldazollum pair at the active site of bromelain is thus, by comparison of the amino acid sequence of bromelain with other cysteine protein ases, likely to have a different conformation from that in (he cysteine proteinases (hat aie tightly inhibited by cystatin [45]. Bromelain also distinguishes itself from other cysteine protein ases by its slow inhibition by the irreversible inhibitor of cysteine oroteinases E-64 rW-ft 3-fraw-cari)OKVOxiran-2 BrboiwlVL-leucvn-amido 4-... 

Estimation of the glomerular filtration rate (GFR) is considered a sensitive index of functional nephron mass (Newman and Price 1999). Point measurements of the plasma levels of several endogenous small molecules (urea, creatinine, 2-(a-mannopyranosyl)-L-tryptophan) or small (less than 66 kDa) proteins (cystatin C (y-trace), prostaglandin D synthase (15-trace protein), ai-microglobulin, p2-microglobulin, and retinol binding protein) have been used to assess GFR in many species. 

Newman DJ, Price CP (1999) Renal function and nitrogen metabolites. In Burris CA, Ashwood ER (eds) Tietz Textbook of Clinical Chemistry, 3rd edn. W.B. Saunders Company, Philadelphia, pp 1204-1270 Pergande M, Jung K (1993) Sandwich enzyme immunoassay of cystatin C in serum with commercially available antibodies. Clin Chem 39 1885-1890... 

DNA sequence The nucleotide sequence data are available from the EMBL, GenBank, and DDBJ Nucleotide Sequence Databases under accession number X52255 Half-life About 20 min (experimentally determined for human cystatin C in rat plasma. The similarity in distribution volume and renal clearance between human cystatin C and acknowledged markers of human glomerular filtration, i.e., iohexol and 51 Cr-EDTA, suggests that the substances are eliminated at the same rate in humans with a half-life of approximately 2 h in individuals with normal renal function)... 

Cystatin refers to a diverse family of protein cysteine protease inhibitors. There are three general types of cystatins Type 1 (stefens), which are primarily found in the cytoplasm but can appear in extracellular fluids Type 2, which are secreted and found in most extracellular fluids and Type 3, which are multidomain protease inhibitors containing carbohydrates and that include the kininogens. Cystatin 3 is used to measure renal function in clinical chemistry. See Barrett, A.J., The cystatins a diverse superfamily of cysteine peptidase inhibitors, Biomed. Biochim. Acta 45,1363-1374,1986 Katunuma, N., Mechanisms and regulation of lysosomal proteolysis, Revis. Biol. Cellular 20, 35-61, 1989 Gauthier, F., Lalmanach, G., Moeau, T. et al., Cystatin mimicry by synthetic peptides, Biol Chem. Hoppe Seyler 373, 465-470, 1992 Bobek, L.A. and Levine,... 

P2.m. The cysteine proteinases are one of four major classes of endoproteinases that possess the ability to degrade intact glomerular basement membranes [144]. All nucleated cells produce cystatin at a stable rate. More than 99% is freely filtered by the glomerulus with little secretion or reabsorption. As a result, it has many of the ideal features for use as a marker of kidney function and eshmate of GFR. Serum cystatin C concentrations demonstrate a good inverse correlation with radionuclide derived measurements of GFR and has been shown in several studies to be superior to creatinine and comparable to iohexol clearances in estimating eGFR [145,146]. 

Cystatin C is nearly completely metabolized by proximal renal tubular cells. As a consequence, under ordinary circumstances there is little to no detectable cystatin C present in the urine. Thus, a true clearance of cystatin C cannot be determined. However, in the presence of tubular damage, cystatin C may be detected in the urine [147,148] and may be more sensitive to early and mild changes of kidney function compared with creatinine [149,150]. In this regard, elevation in serum cystatin C consistent with AKI, defined by at least a 50% increase from baseline, was evident 1-2 days prior to changes in SCr [151]. Finally, in patients with AKI, elevated urinary cystatin C was highly predictive of subsequent need for acute renal replacement therapy and outperformed several other urinary biomarkers in some studies [152]., but not in others [152a]... 

Flerget-Rosenthal S, van Wijk JA, Brocker-Preuss M, Bokenkamp A. Increased urinary cystatin C reflects structural and functional renal tubular impairment independent of glomerular filtration rate. Clin Biochem 2007 27 April [Epub ahead of print].This study provides evidence for urinary cystatin C as a biomarker for tubular injury. 

Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function a metaanalysis. Am J Kidney Dis 2002 40 221-226. 

Wasen E, Suominen P, Isoaho R, Matilia K, Virtanen A, Kivela SL, et aL Serum cystatin C as a marker of kidney function in an elderly population. Clin Chem 2002 48 1138-40. 

Randers E, Erlandsen EJ. Serum cystatin C as an endogenous marker of the renal function—A review. CUn Chem Lab Med 1999 37 389-395. 

Akbas SH, Yavuz A, Ttmcer M, et al. Serum cystatin C as an index of renal function in kidney transplant patients. Transplant Proc 2004 36 99-101. Brandle E, Sieberth HG, Hautman RE. Effect of chronic dietary protein intake on the renal function in healthy subjects. Eur J Qin Nutr 1996 50 734-740. 

---