Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations

Background. Low-level lead exposure is widespread and has been implicated as a chronic kidney disease (CKD) risk factor. However, studies evaluating associations of lead dose with newer, potentially more accurate, estimates of kidney function, in participants with a wide range of glomerular filtration rates (GFRs), are scarce. Methods. We compared associations of blood lead and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C single variable, multivariable and combined creatinine/cystatin C equations in 3941 adults who participated in the 1999-2002 National Health and Nutrition Examination Survey cystatin C subsample. Results. Geometric mean blood lead was 1.7 mu g/dL. After multivariable adjustment, differences [95% confidence interval (CI)] in mean eGFR for a doubling of blood lead were -1.9 (-3.2, -0.7), -1.7 (-3.0, -0.5) and -1.4 (-2.3, -0.5) mL/min/1.73 m(2), using the cystatin C single variable, multivariable and combined creatinine/cystatin C equations, respectively, reflecting lower eGFR with increased blood lead. The corresponding differences (95% CI) were -0.9 (-1.9, 0.02) and -0.9 (-1.8, 0.01) using the creatinine-based MDRD and CKD-EPI equations, respectively. In participants aged >= 60 years, differences in mean eGFR ranged from -3.0 to -4.5 mL/min/1.73 m(2), and odds of reduced eGFR (< 60 mL/min/1.73 m(2)) were increased for all estimates of GFR. Conclusions. These results support the inclusion of cystatin C-based eGFR in future lead research and provide additional evidence for environmental lead exposure as a CKD risk factor.