Lead, at low levels, accelerates arteriolopathy and tubulointerstitial injury in chronic kidney disease.

Chronic lead exposure has been epidemiologically linked with hypertension and renal disease. Clinical studies suggest that low lead levels may contribute to renal progression. However, experimental studies have not examined whether low levels of lead accelerate progression in experimental chronic renal disease. Sprague-Dawley rats were administered lead (L; 150 ppm in drinking water, n = 16) for 4 wk, followed by remnant kidney (RK) surgery with continuation of lead for an additional 12 wk; control rats (n = 9) were treated similarly but did not receive lead. Lead treatment was well tolerated and resulted in modest elevations in whole blood lead levels (26.4 +/- 4.5 vs. 1 +/- 0 mug/dl, week 16, P < 0.001). Lead treatment was associated with higher systolic blood pressure (P < 0.05) and worse renal function (creatinine clearance 1.4 +/- 0.4 vs. 1.8 +/- 0.5 ml/min, RK+L vs. RK, P < 0.05), and with a tendency for greater proteinuria (6.6 +/- 6.1 vs. 3.6 +/- 1.5 mg protein/mg creatinine, RK+L vs. RK, P = 0.08). While glomerulosclerosis tended to be worse in lead-treated rats (37.6 +/- 11 vs. 28.8 +/- 2.3%, RK+L vs. RK, P = 0.06), the most striking finding was the development of worse arteriolar disease (P < 0.05), peritubular capillary loss (P < 0.05), tubulointerstitial damage, and macrophage infiltration (P < 0.05) in association with significantly increased renal expression of monocyte chemoattractant protein-1 mRNA. In conclusion, lead accelerates chronic renal disease, primarily by raising blood pressure and accelerating microvascular and tubulointerstitial injury.