Cystatin C TechNotes

Cystatin C is a low moleclar weight (13.4 kDa) protein that functions as an inhibitor of various cysteine proteases in the bloodstream. It inhibits both endogenous proteases, such as lysosomal cathepsins, and proteases of parasites and microorganisms. Cystatin C binds to the target molecule in μM to the sub pM range in a competitive reversible manner (1). Due to its important function, cystatin C is expressed at the stable levels by most of the nucleated cells. Cystatin C consists of 120 amino acid residues encoded by a 7.3 kb gene located in chromosome 20 (2). The Leu68Gln mutation in the cystatin C protein sequence is directly linked to the development of hereditary cystatin C amyloid angiopathy (HCCAA) in which the patients suffer from repeated cerebral hemorrhages (3).

Cystatin C is known in clinical practice as a well-described serum marker of renal failure that is not dependent on age, sex or lean muscle mass (4, 5). At the same time, cystatin C is becoming acknowledged as a marker of elevated risk of death from cardiovascular complications – myocardial infarction and stroke (5). A stable production rate and free filtration by the renal glomeruli due to the low molecular weight, and positive charge (pI 9.3) are strong advantages of cystatin C as a serum marker of renal function in comparison to other analytes that are used today in clinical practice. Creatinine-based equations to estimate the glomerular filtration rate (GFR) are sensitive to some non-renal factors, such as age, sex, race and lean muscle mass. There is a growing number of reports demonstrating that cystatin C is more preferable than creatinine for the measurement of GFR, so long as it does not depend on all of these factors (5).

Cystatin C is also a more sensitive marker of mild renal dysfunction than creatinine (6). The concentrations of plasma (serum) cystatin C in healthy individuals range from 0.8 to 1.2 mg/l, depending on measurement methods (7). Increased cystatin C serum levels are almost exclusively associated with a reduction in GFR. Serum concentrations of cystatin C are increased approximately 2-fold during various renal disorders (7). An elevated serum cystatin C level is also a strong predictor of the risk of death and cardiovascular events in elderly persons (5).

The urinary concentrations of cystatin C are low (100 μg/l for healthy subjects) since the protein is metabolized by the proximal tubule after filtration in the renal glomerulus. However, the concentrations of cystatin C in urine from patients with renal tubular disorders are raised by approximately 200-fold (8). Cystatin C that is purified from human urine can be partially truncated, which potentially complicates the application of the urine protein as a standard for immunoassays (9).

HyTest offers everything you need for the development of the cystatin C immunoassay - human recombinant cystatin C, native human cystatin C purified from human blood, anti-cystatin C polyclonal antibodies, as well as a set of high-affinity monoclonal antibodies that are specific to different epitopes of human cystatin C molecule. We also supply our customers with information regarding the best MAb combinations to be used in sandwich immunoassays for quantitative measurements of cystatin C in body fluids.

References:

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