Experimental model of lead nephropathy. III. Continuous low-level lead administration.
We sought to determine whether continuous low-level lead exposure (100 ppm lead acetate in drinking water) for periods of 1, 3, 6, 9, or 12 mo would produce adverse effects on kidney function or morphology in rats. Maximum blood lead levels in experimental animals were reached at 3 mo and averaged 29.4 +/- 4.1 micrograms/dl. Glomerular filtration rate, determined by single-injection 125I-iothalamate clearance, was found to be significantly increased above pair-fed controls at 1 and 3 mo, but it was normal at other time periods. Levels of urinary N-acetyl-beta-D-glucosaminidase exceeded levels found in controls at all time periods, except at 12 mo, when the normal increase with aging obscured differences between experimental animals and controls. In contrast, urinary ligandin (glutathione S transferase), a more specific marker of metal-associated proximal tubular injury, was normal at all time periods. Proximal tubular nuclear inclusion bodies were sparse and were observed only at 1 and 3 mo. There were no other pathological alterations in the kidneys, except at 12 mo, at which time mild tubular atrophy and interstitial fibrosis were seen. Therefore, low-level lead exposure in rats produced no significant changes in renal function and produced only mild alterations in renal morphology after 12 mo. The absence of changes in urinary ligandin accorded with the relative absence of morphological changes, whereas the observed increases in urinary N-acetyl-beta-D-glucosaminidase suggest that this enzyme may be an overly sensitive indicator of tubular injury.
Khalil-Manesh
F
F
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Gonick
H C
HC
Cohen
A H
AH
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001284:Atrophy; D001835:Body Weight; D004195:Disease Models, Animal; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D005982:Glutathione Transferase / Q000652:urine; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D007677:Kidney Function Tests; D008297:Male; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000097:blood / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014874:Water Pollutants, Chemical / Q000009:adverse effects*
D009942:Organometallic Compounds; D014874:Water Pollutants, Chemical; D005982:Glutathione Transferase; D000118:Acetylglucosaminidase; C008261:lead acetate