Ischemic damage and repair in the rat proximal tubule: Differences among the S1, S2, and S3 segments

https://www.kidney-international.org/article/S0085-2538(15)57148-2/pdf

The cell biology of ischemic renal injury

Acute renal failure was induced in male rats by the subcutaneous injection of 4 mg HgCl2 per kg body weight. Enzyme activities of the proximal tubule were studied histochemically at six time intervals from 15 min to 24 h. The enzymes studied were alkaline phosphatase, 5′-nucleotidase, acid phosphatase, α-glycerophosphate dehydrogenase (NAD-independent), malic dehydrogenase, succinic dehydrogenase, latic dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase. Decreases in activity were observed for alkaline phosphatase and 5′-nucleotidase after 15 min. Acid phosphatase was decreased after 30 min. These three enzymes returned to control levels after 3 h, but malic dehydrogenase and α-glycerophosphate dehydrogenase were decreased at this time interval. Succinic dehydrogenase was first decreased after 6 h. The earliest morphological changes detectable by light microscopy were observed in pars recta tubules in the medullary rays after 6 h, a time when all enzymes studied showed widespread decreased activity throughout the proximal tubule. After 24 h, the pars convoluta appeared morphologically normal but the pars recta was necrotic and exhibited calcification, whereas enzyme activity was decreased (absent in some cases) in both pars convoluta and pars recta.

Studies on the pathophysiology of acute renal failure. II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride.

Cis-diamminedichlorplatinum-induced acute renal failure in the rat

Acute renal failure was induced in male rats by the subcutaneous injection of 4 mg HgC12 per kg body weight. Changes in the proximal tubule were studied by light and electron microscopy at six time intervals from 15 min to 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 proximal tubule (pars convoluta and pars recta). 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 pars recta 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 pars recta in the outer stripe of the outer medulla. However by 24 h necrosis was widespread throughout the pars recta, yet changes in the proximal convoluted portion were minimal. A significant azotemia, decreased GFR and increased FENa+ and FEK+ occurred at 6 and 24 h after HgC12 injection. Thus HgC12 at 4 mg per kg body weight produced reproducible renal failure and necrosis involving the pars recta of every nephron but necrosis did not begin in the pars recta until after 6 h while acute renal failure was probably initiated much earlier. The following hypothesis is presented. HgC12 initially interacts with the entire proximal tubule. Although injury is sublethal in the pars convoluta it is responsible for greatly diminished sodium reabsorption and is related to the pathogenesis of the renal failure 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 renal failure. The development of necrosis in the pars recta appears to be a relatively late event, possibly due to further accumulation of Hg++ in this region. In any case, the necrosis appears pathogenetically dissociable from the mechanism of acute renal failure.

Studies on the pathophysiology of acute renal failure. I. Correlation of ultrastructure and function in the proximal tubule of the rat following administration of mercuric chloride

The segmentation of the proximal tubules in the kidney of the female rat was studied by means of enzyme histochemical reactions and the results compared with those observed in the male and recently described by Jacobsen and Jorgensen (1973a). Reactions were performed for the following soluble, coenzyme-dependent oxido-reductases: glucose 6-phosphate dehydrogenase, α-glycerophosphate dehydrogenase, 3 α-hydroxysteroid dehydrogenase, NAD-as well as NADP-dependent isocitrate dehydrogenases, NAD-dependent malate dehydrogenase, NADP-dependent, decarboxylating malate dehydrogenase, uridine diphosphate glucose dehydrogenase. Measures were taken to reduce enzyme diffusion and eliminate interference from tissue tetrazolium reductases. Furthermore, reactions were performed for a number of less soluble or insoluble enzymes: glucose 6-phosphatase, mitochondrial α-glycerophosphate dehydrogenase, β-hydroxybutyrate dehydrogenase, succinate dehydrogenase and tetrazolium reductases.

Jacobsen No

Papers

Further enzyme histochemical observations on the segmentation of the proximal tubules in the kidney of the male rat.