Comparison of Two Creatinine-Based Estimating Equations in Predicting All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes

OBJECTIVE

To compare the performance of two glomerular filtration rate (GFR)-estimating equations in predicting the risk of all-cause and cardiovascular mortality in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

We followed 2,823 type 2 diabetic outpatients for a period of 6 years for the occurrence of all-cause and cardiovascular mortality. GFR was estimated using the four-variable Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

RESULTS

At baseline, an estimated GFR (eGFR) <60 mL/min/1.73 m² was present in 22.0 and 20.2% of patients using the MDRD study equation and the CKD-EPI equation, respectively. A total of 309 patients died during the follow-up (152 patients from cardiovascular causes). Both creatinine-based equations were associated with an increased risk of all-cause and cardiovascular mortality. However, the CKD-EPI equation provided a more accurate risk prediction of mortality than the MDRD study equation. Receiving operating characteristic curves showed that the areas under the curve (AUCs) for all-cause mortality (AUC 0.712 95% CI 0.682–0.741]) and cardiovascular mortality (0.771 0.734–0.808]) using eGFR_CKD-EPI were significantly greater (P < 0.0001 by the z statistic) than those obtained by using eGFR_MDRD (0.679 0.647–0.711] for all-cause mortality and 0.739 0.698–0.783] for cardiovascular mortality).

CONCLUSIONS

Our findings suggest that the estimation of GFR using the CKD-EPI equation more appropriately stratifies patients with type 2 diabetes according to the risk of all-cause and cardiovascular mortality compared with the MDRD study equation.Chronic kidney disease (CKD) is a major public health problem because its prevalence is rapidly increasing worldwide and it is strongly associated with increased risks of end-stage renal disease, death, cardiovascular disease (CVD), and hospitalization (1–5). Glomerular filtration rate (GFR) is the best overall measure of kidney function. Current diagnosis, evaluation, and management of CKD routinely rely on estimates of GFR (eGFRs) usually derived from creatinine-based equations such as the Modification of Diet in Renal Disease (MDRD) study equation, which incorporates information on serum creatinine concentration, age, sex, and race (1,6,7). This equation is the most commonly used method for estimating kidney function in routine clinical practice. Its prognostic value has been validated in several studies and populations (1,6,7). Decreased eGFR_MDRD has been shown to be an important risk factor for death, CVD events, and other adverse clinical outcomes, specifically in patients with a GFR level <60 mL/min/1.73 m² (1–5). However, despite its widespread use, it is known that the major limitations of the MDRD study equation are imprecision and systematic underestimation of measured GFR (bias) at higher values (1,6,7).The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) investigators recently developed and validated a new equation to improve the estimation of GFR (eGFR_CKD-EPI) by using a large database pooled from 10 studies (8). This equation, which uses the same four variables as the MDRD study equation (i.e., serum creatinine level, age, sex, and race), has been shown to be more precise and accurate than the MDRD study equation in estimating measured GFR, especially at higher GFR values (8). Improved accuracy of the CKD-EPI equation could have important implications for public health and clinical practice (8). In addition, some large population-based cohort studies have recently shown that the CKD-EPI equation also has superior accuracy in classifying individuals at risk for CVD events and death compared with the MDRD study equation (9–11).However, the CKD-EPI equation might not work equally well in people at high CVD risk, such as type 2 diabetic individuals. Whether the use of the CKD-EPI equation provides more accurate prognostic information than the MDRD study equation with respect to the risk of all-cause and CVD mortality in patients with type 2 diabetes is currently unknown. Thus, the aim of this prospective, longitudinal study was to compare the performance of the MDRD study equation and the CKD-EPI equation in predicting all-cause and CVD mortality in a large sample of type 2 diabetic individuals during a follow-up period of 6 years.