Potentiation of aminoglycoside nephrotoxicity by vitamin-D-induced hypercalcemia.
The effect of 1,25(OH)2 vitamin D3-induced hypercalcemia on the course of aminoglycoside nephrotoxicity in the rat was studied. Daily gentamicin, 100 mg/kg body weight, was administered subcutaneously concomitant with 1,25(OH)2 vitamin D3, 50 ng s.c. to male Sprague-Dawley rats. This group was compared to rats injected with gentamicin alone, 1,25(OH)2 vitamin D3 alone, and an ethanol vehicle as a control. Structural and functional parameters of acute renal failure were assessed following 4, 6 and 7 days of treatment. Severe morphologic evidence of tubular injury was documented on day 6 in the group injected with gentamicin and 1,25(OH)2 vitamin D3. Correlative functional and metabolic evidence of tubular cell deterioration occurred in this group on day 7 as represented by an elevated blood urea nitrogen (BUN), 198 +/- 14 mg/dl (p less than 0.001 compared to all other groups), a heightened mean renal cortical homogenate calcium, 1,028.3 +/- 304.8 nmol/mg protein (p less than 0.05 or better compared to all other groups), and significantly increased mean cortical mitochondrial calcium content, 796.3 +/- 116.5 nmol/mg protein (p less than 0.01 in relation to all other groups). Elevated total serum calcium to a level of 11.9 +/- 0.2 mg/dl (p less than 0.001 compared to control group) developed in the gentamicin/1,25(OH)2 vitamin D3 group on day 4, 2 days prior to pronounced structural damage, and continued to be elevated through day 7. No difference in serum phosphorus levels, however, developed between control and gentamicin-plus-vitamin-D-treated animals except on day 7 when severe renal failure developed in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Cohen
R
R
Department of Medicine, VA Medical Center, Ann Arbor, Mich.
Johnson
K
K
Humes
H D
HD
D000818:Animals; D002118:Calcium / Q000032:analysis; D003404:Creatinine / Q000097:blood; D004357:Drug Synergism; D005839:Gentamicins / Q000097:blood / Q000633:toxicity*; D006934:Hypercalcemia / Q000150:complications*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007672:Kidney Cortex / Q000032:analysis; D008297:Male; D008928:Mitochondria / Q000032:analysis; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000633:toxicity*
D005839:Gentamicins; D014807:Vitamin D; D010758:Phosphorus; D003404:Creatinine; D002118:Calcium