Renal amino acid transport in immature and adult rats during chromate and cisplatinum-induced nephrotoxicity

The effects of sodium dichromate (chromate; 1 mg/100 g b. wt. s.c.) and cis diamminedichloroplatinum(II) (CP; 0.6 mg/100 gb.wt. i.p.) on renal amino ac id excretion and plasma amino acid composition were investigated in 10- and 55-day-old anaesthetised rats. On the basis of diuresis experiments on con scious rats the mentioned doses and times (1(st) day after chromate in both age groups and in 10-day-old rats after CP and 3(rd) day after CP in adult rats) were found out to be optimal for the characterisation of amino acid transport after heavy metal poisoning. Interestingly, in conscious 10-day-o ld rats chromate nephrotoxicity is not detectable after 1 mg/100 g b. wt. w hereas all of the other experimental groups showed nephrotoxic effects of c hromate and CP in conscious rats. Urine volumes are lower, but not signific antly, in anaesthetised immature rats, independently of the administered ne phrotoxin. But GFR is significantly lower in 10-day-old rats, both in contr ols and after CP, whereas after chromate GFR is significantly reduced only in adult rats and age differences disappeared. In principle the renal fract ional excretion (FE) of amino acids was distinctly higher in immature rats as a sign of lower amino acid reabsorption capacity. Nevertheless, the amin o acid plasma concentrations were relatively high in immature rats. However , both chromate and CP did not distinctly influence amino acid plasma conce ntrations. But in both age groups the administration of chromate and CP sig nificantly decreased amino acid reabsorption capacity (increase in FE) as a sign of nephrotoxicity, most pronounced in adult rats after CP. The invest igation of renal amino acid handling confirms (1) that both CP and chromate are nephrotoxins, (2) that CP was more nephrotoxic in 55-day-old animals c ompared to immature rats as could be demonstrated before using other parame ters for nephrotoxicity testing and showed (3) that determination of renal amino acid handling is a highly sensitive marker for nephrotoxicity testing , especially in immature rats.