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Cystatin C

Chronic kidney disease (CKD) is typically defined as GFR less than 60 mL/min/1.73 m2 or urinary albumin-creatinine ratio (ACR) greater than or equal to 30 mg/g that is present for 3 months or more.

In 2021, the National Kidney Foundation and American Society of Nephrology Task Force recommended that all US clinical laboratories adopt the CKD Epidemiology Collaboration 2021 eGFR equations without race. Estimated GFR (eGFR) is most commonly estimated using plasma creatinine concentration because it is released into the bloodstream at a relatively constant rate and is filtered by the kidneys. Plasma creatinine concentration can be influenced by factors other than kidney function. Low muscle mass, vegetarian diet, lower extremity amputation, advanced heart failure, and liver failure decrease plasma creatinine levels, resulting in an eGFR that is higher than the actual GFR. Conversely, plasma creatinine levels may be higher in very muscular individuals, resulting in an eGFR that is lower than the actual GFR. Recent ingestion of cooked meat and use of medications that inhibit proximal tubule secretion of creatinine (such as trimethoprim, dronedarone, cimetidine, and tyrosine kinase inhibitors) can elevate serum creatinine, leading to a reduction in eGFR that is not due to a true decrease in kidney filtration function.

In patients with these medical conditions, plasma cystatin C can used to more accurately estimate eGFR. Cystatin C is a low-molecular-weight proteinase inhibitor protein (13,250 Daltons) that is produced at a constant rate by nucleated cells and freely filtered by the glomerulus.  It is not affected by age, gender, race, muscle mass, or diet. However, obesity, hypothyroidism, cigarette smoking, and use of systemic corticosteroids are associated with higher cystatin C concentrations, resulting in an eGFR that is lower than actual GFR.

Like serum creatinine, non-race-based formulas have been developed to estimate GFR from cystatin C and creatinine levels. These formulas perform at least as well as those based on creatinine to estimate GFR and may be better in patients with abnormally low or high body mass.

Reference range is 0.63 to 1.21 mg/L for adults.

Specimen requirement is a red top tube of blood.

References

Shilpak M, Inker L, Coresh J, Serum Cystatin C for Estimation of GFR. JAMA, published online August 8, 2022

Inker LA, Eneanya ND, Coresh J, et al; Chronic Kidney Disease Epidemiology Collaboration. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385 (19):1737-1749. doi:10.1056/NEJMoa2102953.

Gutierrez OM, Sang Y, Grams ME, et al; Chronic Kidney Disease Prognosis Consortium. Association of estimated GFR calculated using race-free equations with kidney failure and mortality by black vs non-black race. JAMA. 2022;327(23):2306-2316. doi:10.1001/jama.2022.8801

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