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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/F1391    most recent 00216.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Roncal, C. Articles by Johnson, R. J. Search for Related Content PubMed PubMed Citation Articles by Roncal, C. Articles by Johnson, R. J.

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

Division of Nephrology, Hypertension, and Transplantation, University of Florida, Gainesville, Florida

Submitted 10 May 2007 ; accepted in final form 20 July 2007

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 µg/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.

arteriolosclerosis; interstitial inflammation; hypertension; uric acid