Relationships and Clinical Utility of Creatinine, Cystatin C, eGFRs, GFRs, and Clearances

This review addresses techniques for glomerular filtration rate (GFR), either measured by clearance tests such as with creatinine, iothalamate, inulin, or iohexol [measured GFR (mGFR)] or calculated by equations that determine the estimated GFR (eGFR) from serum measurements of creatinine and/or cystatin C. However, mGFR tests are slow and impractical for routine use. Therefore, calculations of eGFRs have been developed that have advantages over the mGFRs. The eGFR is a serum creatinine and/or cystatin C adjusted for age, sex, and race, with mathematical manipulations to produce an average numerical agreement with the mGFR. However, all comparisons between eGFR and mGFR show wide scatter that appears to be related to the large variability of the mGFR. Procedures for mGFR often do not agree with each other and have both wide population variation (similar to plasma creatinine and cystatin C) and within-individual variation that is much larger than creatinine or cystatin C. Whether the measured GFR is even equivalent to serum creatinine and/or cystatin C for detecting early clinical changes in chronic kidney disease will be addressed. Procedures for measuring GFR are tedious and expensive, and have both wide population variation (similar to plasma creatinine and cystatin C), and within-individual variation that is much larger than either creatinine or cystatin C. Because the normal range for mGFR overlaps considerably with the stages 1 and 2 of chronic kidney disease, mGFR has significant clinical limitations. Instead of trying to mimic mGFRs, the focus should be on using eGFRs on their own clinical merits to detect impaired kidney function.