From the Guidelines
Cystatin is a family of proteins that function as cysteine protease inhibitors in the body, with cystatin C being a valuable biomarker for kidney function, particularly for estimating glomerular filtration rate (GFR) in a more reliable manner than creatinine, as supported by recent recommendations 1. The role of cystatins in the body is multifaceted, including regulating protein breakdown by inhibiting enzymes called cathepsins. Cystatin C, the most well-known member, is produced by all nucleated cells and found in various body fluids, including blood, cerebrospinal fluid, and urine. Key characteristics of cystatin C include:
- Not significantly affected by muscle mass, diet, or gender, making it a more reliable marker than creatinine in certain populations, such as the elderly, children, or those with reduced muscle mass.
- Elevated levels typically indicate reduced kidney function, highlighting its importance in clinical medicine for assessing kidney health.
- Implicated in various pathological processes beyond kidney disease, including cancer progression, neurodegenerative diseases, and cardiovascular disorders, due to its role in regulating proteolytic activity. Recent guidelines, such as those from the NKF-ASN Task Force 1, recommend the increased use of cystatin C for confirming eGFR in adults at risk for or with chronic kidney disease (CKD), emphasizing its potential to support better clinical decisions when combined with other filtration markers like creatinine. However, the availability of cystatin C measurements in all laboratories is a challenge, as noted in more recent discussions 1, which may impact its immediate adoption for rapid decision-making in all settings.
From the Research
Definition and Function of Cystatin
- Cystatin is an endogenous inhibitor of lysosomal cysteine proteinases, playing a role in several normal and pathological processes 2.
- It belongs to a superfamily of proteins with wide occurrence in tissues, acting as a natural cysteine protease inhibitor 3.
- Cystatin C, a specific type of cystatin, is a small protein molecule produced by virtually all nucleated cells, with its main biological role being the extracellular inhibition of cathepsins 4.
Role in Cancer Progression
- Cystatins have been implicated in the malignant progression of various human tumors, with studies suggesting they may function as either tumor suppressors or tumor promoters 2, 3.
- They affect all stages of cancer progression, including tumor growth, apoptosis, invasion, metastasis, and angiogenesis 5.
- Altered expression of cystatins in cancer can result in harmful excessive cysteine peptidase activity, making them potential targets for the development of new anti-tumor drugs 5.
Biochemistry and Clinical Role
- Human cystatin C is a single non-glycosylated polypeptide chain consisting of 120 amino acid residues, with a molecular mass of 13,343-13,359 Da 6.
- It is encoded by the CST3 gene, ubiquitously expressed at moderate levels, and present in all human body fluids 6.
- Cystatin C has been investigated as a marker of kidney dysfunction, demonstrating better diagnostic accuracy than serum creatinine in discriminating normal from impaired kidney function 6.