Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort

Background: Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease. Study Design: Prospective population-based cohort. Setting & Participants: 4,341 individuals aged 46 to 67 years enrolled into the Malmo Diet and Cancer Study-Cardiovascular Cohort (19911994) and 2,567 individuals subsequently followed up (2007-2012). Predictor: Blood lead concentrations in quartiles (Q1-Q4) at baseline. Outcomes: Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry. Measurements: Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data. Results: At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) mu g/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6 mL/min/1.73 m(2) (based on creatinine) and 24 mL/min/1.73 m(2) (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined. Limitations: Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding. Conclusions: Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure.