1G96, 1R4C, 1TIJ, 3GAX, 3NX0, 3PS8, 3QRD, 3S67, 3SVA147113010ENSG00000101439ENSMUSG00000027447P01034P21460NM_001288614NM_000099NM_009976NP_000090NP_001275543NP_034106Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin, or neuroendocrine basic polypeptide),[5] a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function.

It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's disease.

Glomerular filtration rate (GFR), a marker of kidney health, is most accurately measured by injecting compounds such as inulin, radioisotopes such as 51chromium-EDTA, 125I-iothalamate, 99mTc-DTPA or radiocontrast agents such as iohexol, but these techniques are complicated, costly, time-consuming and have potential side-effects.

Cystatin C has a low molecular weight (approximately 13.3 kilodaltons), and it is removed from the bloodstream by glomerular filtration in the kidneys.

[10][11][12] Although studies are somewhat divergent, most studies find that cystatin C levels are less dependent on age, gender, ethnicity, diet, and muscle mass compared to creatinine,[13][14] and that cystatin C is equal or superior to the other available biomarkers in a range of different patient populations, including diabetic patients, in chronic kidney disease (CKD), and after kidney transplant.

[17] The UK's National Institute for Health and Care Excellence (NICE) guideline for the assessment and management of CKD in adults concluded that using serum cystatin C to estimate GFR is more specific for important disease outcomes than use of serum creatinine, and may reduce overdiagnosis in patients with a borderline diagnosis, reducing unnecessary appointments, patient worries, and the overall burden of CKD in the population.

[19][20] Cystatin C levels have been reported to be altered in patients with cancer,[21][22][23] (even subtle) thyroid dysfunction[24][25][26] and glucocorticoid therapy in some[27][28] but not all[29] situations.

[30] However, inflammation does not cause an increase in the production of cystatin C, since elective surgical procedures, producing a strong inflammatory response in patients, do not change the plasma concentration of cystatin C.[medical citation needed] Levels seem to be increased in HIV infection, which might or might not reflect actual renal dysfunction.

[56] Mutations in the cystatin 3 gene are responsible for the Icelandic type of hereditary cerebral amyloid angiopathy, a condition predisposing to intracerebral haemorrhage, stroke and dementia.

Since cystatin 3 also binds amyloid β and reduces its aggregation and deposition, it is a potential target in Alzheimer's disease.

[65] The role of cystatin C in multiple sclerosis and other demyelinating diseases (characterized by a loss of the myelin nerve sheath) remains controversial.

[66] Cystatin C levels are decreased in atherosclerotic (so-called 'hardening' of the arteries) and aneurysmal (saccular bulging) lesions of the aorta.

[86][88] In a large study from the United States National Health and Nutrition Examination Survey, the reference interval (as defined by the 1st and 99th percentile) was between 0.57 and 1.12 mg/L.

[85] Other studies have found that in patients with an impaired renal function, women have lower and blacks have higher cystatin C levels for the same GFR.

[90] Based on a threshold level of 1.09 mg/L (the 99th percentile in a population of 20- to 39-year-olds without hypertension, diabetes, microalbuminuria or macroalbuminuria or higher than stage 3 chronic kidney disease), the prevalence of increased levels of cystatin C in the United States was 9.6% in subjects of normal weight, increasing in overweight and obese individuals.

The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions.

[97][98] Use of serum creatinine and cystatin C was found very effective in accurately reflecting the GFR in a study reported in the July 5, 2012, issue of the New England Journal of Medicine.