Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate

Abstract

Context: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking.

Objective: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics.

Design, setting, and participants: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012.

Main outcome measures: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years).

Results: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts.

Conclusion: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

Figure 1

Distribution based on kernel density estimation (proportion is for each integer eGFR) (A), and adjusted hazard ratios and 95% CIs (shaded areas or whisker plots) of all-cause mortality (B), cardiovascular mortality (C), and ESRD (D) according to eGFR by the CKD-EPI equation (red line) and the MDRD equation (black line) with eGFR 95 ml/min/1.73 m² as a reference (diamond). Vertical lines in panel A define GFR categories used for CKD staging.^, Dots in panels B-D represent statistical significance (P<0.05). *Adjustments were for age, sex, race/ethnicity, smoking, history of CVD, systolic blood pressure, diabetes, serum total cholesterol concentration, body mass index, and albuminuria (log-ACR, log-PCR or categorical dipstick proteinuria [negative, trace, 1+, ≥2+]).

Figure 2

Reclassification across eGFR categories by the CKD-EPI equation from eGFR categories based on the MDRD Study equation in the general population cohorts. The blue and red bars indicate upward reclassification to a higher eGFR category and downward reclassification to a lower eGFR category, respectively. Data are given as number (percentage) of participants who were reclassified.

Figure 3

Meta-analyzed NRI (middle of data marker) and 95% CI (horizontal line) for the three outcomes based on eGFR categories overall and in subgroups according to demographic variables included in both equations and presence or absence of diabetes and hypertension (general population cohorts). The sizes of the data markers are proportional to the inverse of the variance of the NRIs. NRI was calculated as follows: NRI = Pr(down to lower eGFR category|events) + Pr(up to higher eGFR category|no events) – Pr(down to lower eGFR category|no events) – Pr(up to higher eGFR category|events). Positive NRI values favor the CKD-EPI equation.