Acute cisplatin nephrotoxicity in the rat. Evidence for impaired entry of sodium into proximal tubule cells.

The earliest phase of cisplatin nephrotoxicity involves natriuresis due to impaired sodium reabsorption by the proximal tubule. To define the cell mechanism of this transport lesion, electron microprobe X-ray analysis was used to determine changes in the electrolyte composition of proximal tubule cells in kidneys taken from rats treated acutely with cisplatin (1 mg/100 g body weight). Compared to control animals injected with vehicle, cisplatin treated rats developed significant natriuresis, the fractional excretion of sodium rising over sevenfold. In kidneys removed 90 min following cisplatin, sodium concentration in proximal tubule cells was reduced by 4.2 mmol/kg wet weight, or 19%, compared to control values. When allowance was made for cell shrinkage in cisplatin-treated kidneys by deriving the cell content of sodium (mmol/kg dry weight), the reduction was even greater (28%). These data suggest that cisplatin reduces proximal tubule sodium reabsorption by inhibiting the entry of sodium into the cells across the apical membrane.