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

Abstract

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.

Keywords: Biomarkers of chronic kidney disease; Chronic kidney disease; Creatinine clearance; Creatinine excretion; Cystatin C; Estimated glomerular filtration rate; Hyperfiltration; Renal imaging; Serum creatinine.

Figure 1

Modification of Diet in Renal Disease[22] and Chronic Kidney Disease Epidemiology Collaboration[23] formulae for estimating glomerular filtration rate fit to variations in serum creatinine (X axis) and age (Y axis) assuming males of Caucasian race. Note that the CKD-EPI formula yields slightly higher eGFR values with higher serum creatinine values and lower age whereas the MDRD formula leads to significantly higher eGFR values at very low serum creatinine values. MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; eGFR: Estimating glomerular filtration rate.

Figure 2

Modification of Diet in Renal Disease[22] and Chronic Kidney Disease Epidemiology Collaboration[23] formulas for estimating glomerular filtration rate fit to variations in serum creatinine (X axis) and age (Y axis) assuming females of Black race. The CKD-EPI formula yields slightly higher eGFR values with higher serum creatinine values and lower age whereas the MDRD formula leads to significantly higher eGFR values at very low serum creatinine values in this population also. MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; eGFR: Estimating glomerular filtration rate.

Figure 3

Scatterplot demonstrating close relationships between estimating glomerular filtration rate values calculated by the Chronic Kidney Disease Epidemiology Collaboration formula[23] (Y axis) and the Modification of Diet in Renal Disease formula[22] (X axis). Different colors are used to indicate the races and genders depicted in this figure: Yellow indicates Caucasian males, Green Black males, Red Caucasian females, and Purple Black females. A straight line to fit the data minimizes the least square error with an intercept of -1.03 and a beta coefficient of 1.04 achieving an R² value of 0.99. MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; eGFR: Estimating glomerular filtration rate.

Figure 4

Comparison of estimating glomerular filtration rate values obtained by the Modification of Diet in Renal Disease[22] and Chronic Kidney Disease Epidemiology Collaboration[23] formulas in subjects who were enrolled in the NHANES study (Serum creatinine > 0.4 mg/dL, age ≥ 20 year) and the MDRD study[22]. MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration.