Creatinine and cystatin C
eGFR, estimated using either creatinine- or cystatin C-based measurements, is most commonly used to diagnose CKD in clinical practice.
Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism. Because it is produced at a constant rate and is excreted via the kidneys, creatinine serum levels are routinely used to calculate an eGFR (both CKD-EPI 2021 equation as well as the prior 2009 equation).3 However, creatinine levels are influenced by diet and muscle mass. Consequently, eGFR may not accurately reflect GFR in certain patients, such as those who have serious comorbid conditions, have extremes of muscle mass (eg, bodybuilders, individuals who have had an amputation), are malnourished or obese, eat little or no meat, are taking creatinine dietary supplements, or are pregnant.10,11 In addition, some medications can elevate serum creatinine level, including trimethoprim, fenofibrate, H2-blockers, and tyrosine kinase inhibitors.10,11
Cystatin C is a low molecular weight cysteine protease inhibitor that is produced by all nucleated cells and is removed from the bloodstream by glomerular filtration in the kidneys.10,12 If kidney function and GFR decline, blood levels of cystatin C rise. An eGFR calculated using cystatin C may yield a more accurate eGFR for persons with unusually low or high muscle mass or protein intake because it is less influenced by these factors than is creatinine-based eGFR.10,12-14 Notably, a recent study suggested that a cystatin C–based eGFR was a better predictor of adverse events (eg, all-cause mortality, progression to ESRD) than was a creatinine-based eGFR in older patients (>65 years old) with CKD.15
On the other hand, a cystatin C-based eGFR may be more affected by conditions such as thyroid disorders, corticosteroid use, smoking, diabetes, obesity, and inflammation.16-18 Consequently, these factors should be considered when eGFR is determined using cystatin C.