Studies on the pathophysiology of acute renal failure

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Abstract
Acute renal failure [RF] was induced in male rats by s.c. injection of 4 mg HgCl2/kg body wt. Changes in the proximal tubule [PT] were studied by light microscopy and EM at 6 time intervals from 15 min-24 h. Renal function was monitored at 6 and 24 h. Between 15 min and 3 h changes were similar in all regions of the PT (pars convoluta [pc] and pars recta [pr]). Dispersion of cytoplasmic polysome groups was widespread and mitochondrial matrices were condensed in some cells. No changes were noted in the brush border but increased endocytotic activity occurred in some convoluted tubules at 1 and 3 h. At 6 h severe changes had occurred in the pr in the medullary rays. Microvilli of the brush border were focally absent, the mitochondria were swollen and the endoplasmic reticulum was dilated. At this time only subtle changes occurred in the pr in the outer strips of the outer medulla. However by 24 h necrosis was widespread throughout the pr, yet changes in the proximal convoluted portion were minimal. A significant azotemia, decreased GFR [glomerular filtration rate] and increased FE [fractional excretion]Na+ and FEK+ occurred at 6 and 24 h after HgCl2 injection. HgCl2 at 4 mg/kg body wt produced reproducible RF and necrosis involving the pr of every nephron but necrosis did not begin in the pr until after 6 h while acute RF was probably initiated much earlier. HgCl2 initially interacts with the entire PT. Although injury is sublethal in the pc it is responsible for greatly diminished Na reabsorption and is related to the pathogenesis of the RF through feedback mechanisms involving the macula densa and release of renin. This results in renal hemodynamic alterations, decreased GFR and other functional disturbances associated with RF. The development of necrosis in the pr appears to be a relatively late event, possibly due to further accumulation of Hg2+ in this region. The necrosis appears pathogenetically dissociable from the mechanism of acute RF.