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Lead Exposure Accelerates Chronic Kidney Disease

Lead raises blood pressure and injures kidney tissue, accelerating chronic disease in an experimental model

(Bethesda, MD) – As Americans grow more concerned about lead levels found in children’s’ toys, a new study finds that lead exposure accelerates chronic renal disease by raising blood pressure and accelerating injury to kidney tissues and blood vessels. The findings are published in the online edition of the American Journal of Physiology–Renal Physiology.

Lead exposure has long been associated with high blood pressure (hypertension), arteriolosclerosis, kidney disease and gout. Studies in workers exposed to lead have confirmed these associations. Other studies have suggested that even low levels of lead in the blood can be associated with higher frequencies of high blood pressure and chronic kidney disease.

The new study, the first of its kind in an animal model, shows that low level lead exposure accelerates chronic renal disease, primarily by raising blood pressure and accelerating certain kinds of cellular injury. It was conducted by Carlos Roncal, Wei Mu, Sirirat Reungjui, Kyung Mee Kim, George N. Henderson, Xiaosen Ouyang, Takahiko Nakagawa, and Richard J. Johnson, all of the Division of Nephrology, Hypertension, and Transplantation, University of Florida, Gainesville, FL. The study is entitled, “Lead, at Low Levels, Accelerates Arteriolopathy and Tubulointerstitial Injury in Chronic Kidney Disease”. It appears in the online edition of the American Journal of Physiology-Renal Physiology.

Study of Chronic, Low Dose Lead Exposure

The study used male rats which were fed a standard diet. In addition, 16 of the rats consumed drinking water treated with lead acetate (i.e., 150 ppm of lead (L)) for four weeks. The dose of lead administered resulted in mild toxicity and is similar or slightly lower than the levels observed in subjects with occupational exposure. Thereafter they underwent remnant kidney (RK) surgery and afterwards continued on the lead acetate for 12 more weeks.

A control group also underwent RK surgery but without lead acetate. At eight and 12 weeks after surgery, the body weight of all the rodents was measured and systolic blood pressure was assessed. Twelve weeks after RK surgery, kidney tissue was collected for histologic and molecular biologic studies from both groups.

Study Results

Lead treatment was well tolerated and resulted in modest elevations in whole blood lead levels (26.4 ± 4.5 vs. 1 0 µg/dl, wk 16, p ± < 0.001). But low lead level exposure reduced body weight, increased blood pressure and worsened renal dysfunction. Specifically, lead exposure:  

  • was associated with higher systolic blood pressure 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 urinary protein (6.6±6.1 vs. 3.6±1.5 mg protein/mg creatinine, RK+L vs. RK); and
  • while scarring in the renal capillary system tended to be worse in lead treated rats (37.6 ± 11 vs. 28.8 ± 2.3 percent, RK+L vs. RK), the most striking finding was that kidney tissue disease (arteriolar disease, peritubular capillary loss, tubulointerstitial damage and macrophage infiltration) worsened with lead exposure. These developments were associated with the significantly increased renal expression of monocyte chemoattractant protein-1 mRNA.

Conclusions

According to Dr. Johnson, the seior researcher, “This study examined the effect of mild, chronic lead intoxication in an experimental model of chronic renal disease. The dose of lead administered resulted in mild toxicity. This degree of lead poisoning was sufficient to cause higher blood pressures and accelerate the progression of renal failure.”

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.