Cystatin C, Serum/Plasma

Cystatin C measurements, performed with this assay in human serum and plasma are used as an aid for diagnosis and monitoring of kidney‑related
conditions (such as chronic kidney disease, acute kidney injury, or drug‑induced kidney toxicity). Cystatin C is a low‑molecular‑weight (13 kDa) cysteine protease inhibitor. It is produced by all nucleated cells at a constant rate. Elimination from the circulation is almost entirely via glomerular filtration. Also cystatin C
concentration in blood is correlated with glomerular filtration rate (GFR). 

In comparison with proteins used to estimate GFR like creatinine, cystatin C is less dependent on muscular mass, and is less influenced by sex. There is
only little dependency of cystatin C concentration with age in the age range 1 to 50 years whereas the cystatin C concentration of healthy individuals
> 50 years increases with age.

The GFR using plasma or urinary clearance of exogenous filtration markers is the most frequently used criteria in the assessment of renal function. Serum creatinine is currently the most commonly used marker for estimated GFR (eGFR). In comparison, cystatin C has been proposed as being superior and more accurate, because a higher correlation with standard measures of GFR has been consistently found when compared to creatinine. Creatinine concentration is in particular significantly changed by many factors such as muscle mass, diet, gender, age and tubular secretion. However, it is important to consider that cystatin C concentration may still be affected by factors other than GFR, such as thyroid dysfunction, glucocorticoids, and inflammation. Cystatin C has been shown to be
particularly useful in populations where creatinine‑based estimations may be less accurate, such as the elderly, children, and individuals with certain health conditions. Patient groups which benefit most from cystatin C measurements are those with mild to moderate kidney disease and also those in acute renal failure, where toxic drugs have to be administered which are excreted by glomerular filtration, especially people over age 50, children, pregnant women with suspicion of pre‑eclampsia, diabetics, people with diseases of skeletal muscle and renal transplant recipients.

Additionally, Cystatin C measurements have also been associated with the risk assessment for cardiovascular diseases and mortality, providing important prognostic information. Cystatin C has been discussed in particular as a prognostic marker for acute heart failure. Cystatin C equations have been developed to estimate GFR for the diagnosis, evaluation, management, and follow‑up of kidney disease. Current guidelines define chronic kidney disease as kidney damage or decreased GFR (less than 60 mL/min per 1.73 m2 ) for 3 months or more. The 2012 Kidney Disease Improving Global Outcome (KDIGO) guidelines
on CKD suggest calculating eGFR with a cystatin C-based equation for confirmatory testing when creatinine-based eGFR is in the range of 45‑59 mL/min/1.73 m2 and urine albumin is < 30 mg/g creatinine. Combined equations also exist for pediatric subjects. The National Institute for Health and Care Excellence (NICE) guideline recommends considering the use of serum cystatin C based eGFR as an additional diagnostic tool for people with a borderline diagnosis of kidney diseases, and to confirm or rule out chronic kidney disease in people with a creatinine based eGFR of 45‑59 mL/min/1.73 m2 and no proteinuria.