The relationship between acute alterations of tissue Ca++ and the development of acute renal failure and lethal renal tubular cell injury in the kidney was studied. Nephrotoxicity was induced by HgCl2, and its course was modified by prior saline drinking. Both a semiquantitative scale measuring the extent of lethal tubule cell injury and a computerized assessment of numbers of nuclei in Feulgen stained sections of cortex were used for morphologic analysis. The 2 methods agreed very closely with each other, indicating the utility of an automated computerized approach as a rapid, quantitative adjunct for the assessment of lethal cell injury in the kidney. Increases of blood urea nitrogen during 12-24 hr after HgCl2 were associated with increasing extent of lethal cell injury in both saline and water drinking rats. Striking progressive increases of renal cortical Ca++ developed. In both water and saline drinking rats, the increases in tissue Ca++ were significantly associated with increasing blood urea nitrogen levels and extent of lethal cell injury as determined morphologically. However, similar degrees of increased blood urea nitrogen and extensive lethal cell injury were accompanied by substantially lower tissue Ca++ levels in saline drinking rats than in water drinking rats, indicating an independent effect of saline drinking to ameliorate the increases in tissue Ca++ occurring during lethal cell injury in this model. These data provide further insight into the relationship between structural and functional changes during HgCl2 nephrotoxicity and establish the utility of an automated computerized morphometric method for assessing the extent of lethal cell injury.
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