Cystatin C Applications in Kidney Function Assessment

Cystatin C is a low‐molecular‐weight protein produced by all nucleated cells and freely filtered by the glomerulus. Its serum concentration is largely unaffected by muscle mass, diet or gender, making it a reliable endogenous marker of glomerular filtration rate (GFR). Over the past decade, cystatin C has been incorporated into equations for estimating GFR (eGFR), either alone or in combination with creatinine, to improve diagnostic accuracy across diverse patient populations. Combined creatinine–cystatin C equations reduce misclassification of chronic kidney disease (CKD) stages and enhance risk stratification for cardiovascular and all‐cause mortality. Beyond eGFR estimation, cystatin C has revealed new pathophysiological entities such as shrunken pore syndrome, in which selective impairment of mid‐molecule clearance portends higher mortality. Point‐of‐care assays and lateral‐flow immunoassays for rapid cystatin C measurement are under development to enable earlier detection of renal dysfunction in primary and critical care settings. Globally, the adoption of cystatin C‐based assessment holds promise for more equitable and accurate screening, diagnosis and monitoring of CKD, with practical implications for drug dosing, timing of referral to specialist services and evaluation of therapeutic interventions.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Cystatin C Applications in Kidney Function Assessment publication trend

The graph below shows the total number of articles in cystatin c applications in kidney function assessment across all publications each year (not limited to Nature Index journals).

Technical terms

Glomerular filtration rate (GFR): The volume of plasma filtered by the glomeruli per unit time, typically expressed in mL/min/1.73 m², and regarded as the best overall index of kidney function.

Estimated glomerular filtration rate (eGFR): An approximation of GFR calculated from serum biomarkers (creatinine and/or cystatin C) using validated equations.

Cystatin C: A 13 kDa cysteine protease inhibitor produced at a constant rate by nucleated cells, freely filtered by the glomerulus and fully reabsorbed and catabolised by proximal tubular cells.

Shrunken pore syndrome: A filtration disorder characterised by reduced glomerular clearance of mid‐sized proteins compared with small solutes, identified by a low ratio of cystatin C–derived eGFR to creatinine–derived eGFR.

Non‐GFR determinants: Factors unrelated to filtration (for example, inflammation, steroid use or thyroid dysfunction) that can influence serum levels of creatinine or cystatin C and affect eGFR estimates.

References

1. The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study. PLOS Medicine (2017).
2. Shrunken pore syndrome - a common kidney disorder with high mortality. Diagnosis, prevalence, pathophysiology and treatment options. Clinical Biochemistry (2020).
3. Discordances Between Creatinine- and Cystatin C–Based Estimated GFR and Adverse Clinical Outcomes in Routine Clinical Practice. American Journal of Kidney Diseases (2023).
4. Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project. BMC Medicine (2020).
5. Cystatin C: A Primer for Pharmacists. Pharmacy (2020).
6. Development and Evaluation of a Quantitative Fluorescent Lateral Flow Immunoassay for Cystatin-C, a Renal Dysfunction Biomarker. Sensors (2021).