Establishing the presence or absence of chronic kidney disease: Uses and limitations of formulas estimating the glomerular filtration rate

The development of formulas estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease (CKD), which is based on eGFR values and albuminuria. This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based eGFR values and between eGFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury.