Environmental lead exposure and progressive renal insufficiency.

BACKGROUND: Several recent studies show that serum creatinine level or creatinine clearance is inversely associated with blood lead levels. However, the studies did not allow direct inferences about causality.

OBJECTIVE: To evaluate the relation between body lead burden (BLB) and progressive renal insufficiency in patients without previous heavy lead exposure.

DESIGN: A prospective, longitudinal study with a controlled clinical trial.

PATIENTS: One hundred ten patients with chronic renal insufficiency (serum creatinine level, 133-354 micromol/L [1.5-4.0 mg/dL]) and normal BLB (EDTA mobilization tests, <600 microg per 72-hour urine collection) and without a history of previous heavy lead exposure were divided into 2 groups according to BLB: the high-normal BLB group (BLB > or =80 microg and <600 microg) and the low BLB group (BLB <80 microg). Patients were prospectively followed up for 2 years.

MAIN OUTCOME MEASURES: The primary outcome was a 1.5 times increase in the initial creatinine level. The secondary outcome was a change over time in the value of creatinine clearance. At the end of follow-up, a 3-month clinical trial with chelation therapy for patients with high-normal BLB was performed to clarify the role of environmental lead exposure in progressive renal insufficiency.

RESULTS: Fifteen patients (14 in the high-normal BLB group and 1 in the low BLB group) reached the primary outcome within 24 months. Renal outcome was significantly better in the low BLB group (P<.001). From month 12 to month 24, renal function of high-normal BLB patients had a greater rate of progressive renal insufficiency than that of low BLB patients. In the Cox multivariate regression analysis, BLB was the most important risk factor for determining the progression of renal insufficiency. After chelation therapy, significant improvement in renal function was noted. In addition, the effect of improving renal function lasted for more than 12 months in these patients.

CONCLUSIONS: Long-term low-level environmental lead exposure may subtly affect progressive renal insufficiency in the general population. Progressive renal insufficiency may be improved for at least 1 year after lead chelating therapy. Further investigations are needed to clarify this observation.