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)