Longitudinal Assessment of Estimated Glomerular Filtration Rate in Apparently Healthy Adults: A Post hoc Analysis from the JUPITER Study (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)

Abstract

Background Serum creatinine–based estimates of glomerular filtration rate (eGFR) are frequently used to identify patients with chronic kidney disease and assess cardiovascular risk both in clinical trials and in clinical practice. Although change in eGFR may be useful to assess change in renal function in patients with chronic kidney disease, the utility of serum creatinine–based eGFR is uncertain, particularly among individuals with normal or only mildly impaired renal function. Objective The goal of this study was to examine the relationship between baseline serum creatinine and eGFR, as well as changes in these parameters, in apparently healthy adults in a post hoc analysis of data obtained in participants in the JUPITER study (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin). Methods JUPITER was a randomized study of rosuvastatin 20 mg versus placebo in apparently healthy adults with high-sensitivity C-reactive protein levels ≥2.0 mg/L, LDL-C <130 mg/dL, and serum creatinine ≤2.0 mg/dL. Changes from baseline in serum creatinine and eGFR, based on the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, were assessed in the entire population and in subsets classified according to baseline eGFR status. Results Baseline characteristics of the 16,279 JUPITER study participants (mean age, 66 years; 62% men; 72% white; and 58% with a history of hypertension) who had both a baseline and ≥1 postbaseline serum creatinine measurement were similar to the entire population of 17,802 patients who entered the trial. The mean age of the study population was 66 years, 62% were men, 72% were white, and 58% had a history of hypertension. Mean (SD) serum creatinine increased from baseline by 0.08 (0.16) mg/dL and 0.09 (0.14) mg/dL in the rosuvastatin and placebo groups, respectively ( P = 0.001) at year 1 and by 0.09 (0.18) and 0.10 (0.16) mg/dL ( P = 0.0045) at the final visit. Reductions in MDRD and CKD-EPI eGFR were ∼0.5 mL/min/1.73 m 2 greater with placebo than with rosuvastatin ( P < 0.004) at year 1 and the final visit. The magnitude of eGFR change was closely related to baseline eGFR, with greater reductions among subjects with eGFR ≥60 mL/min/1.73 m 2 in both the rosuvastatin and placebo groups. Among those with an eGFR ≥90 mL/min/1.73 m 2 , mean changes at year 1 and final visit ranged from –16 to –23 mL/min/1.73 m 2 with MDRD and CKD-EPI, respectively; in contrast, mean changes were <1 mL/min/1.73 m 2 in subjects with eGFR <60 mL/min/1.73 m 2 . Conclusions In JUPITER, reductions in MDRD or CKD-EPI eGFR levels were greater in study participants with higher baseline eGFR levels but less in the rosuvastatin than in the placebo group. Future studies are required to assess the reliability of serum creatinine–based estimates of GFR to assess change in renal function, particularly among individuals with normal serum creatinine levels. ClinicalTrials.gov identifier: NCT00239681.