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Comparison of Risk Prediction Using the CKD-EPI Equation and the MDRD Study Equation for Estimated Glomerular Filtration Rate
Study Questions:
What is the relative efficacy of an estimated glomerular filtration rate (GFR) computed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the Modification of Diet in Renal Disease (MDRD) Study equation in predicting risk for adverse outcomes in a broad range of populations?
Methods:
A meta-analysis of data from 1.1 million adults (ages ≥18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts was performed. Data transfer and analyses were conducted between March 2011 and March 2012. The main outcome measures were all-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7,644 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 six categories (≥90, 60-89, 45-59, 30-44, 15- 29, and <15 ml/min/1.73 m2) 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 3-5 (estimated GFR <60 ml/min/1.73 m2) was reduced from 8.7% to 6.3%. In estimated GFR of 45-59 ml/min/1.73 m2 by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60-89 ml/min/1.73 m2 by the CKD-EPI equation and had lower incidence rates (per 1,000 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% confidence interval [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 < 0.001). 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.
Conclusions:
The authors concluded that 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.
Perspective:
In this analysis from more than 1 million participants residing in 40 countries or regions, approximately one-fourth of participants were reclassified to a higher estimated GFR category by the CKD-EPI equation compared with the MDRD Study equation. The CKD-EPI creatinine-based equation more accurately classified individuals with respect to risk of mortality and ESRD compared with the MDRD Study equation. Importantly, a better risk categorization by the CKD-EPI equation compared with the MDRD Study equation was consistent in almost all subgroups defined by age, sex, race/ethnicity, and clinical characteristics. Given more accurate GFR estimation, lower CKD prevalence estimates, and better risk categorization by the CKD-EPI equation without additional laboratory costs, its implementation for estimated GFR reporting in clinical practice may contribute to more efficient and targeted prevention of CKD-related adverse outcomes.
Keywords: Renal Insufficiency, Follow-Up Studies, Glomerular Filtration Rate, Hypertension, Diabetes Mellitus
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