Phospholipid metabolism during renal regeneration after acute tubular necrosis

Renal function, structure, and membrane metabolism were studied during regeneration of proximal tubular cells in rats. A reversible syndrome of nonoliguric acute renal failure was induced by the intravenous administration of a low dose of mercuric chloride (1.0 mg Hg/kg). At day 1 there was a marked increase in serum urea nitrogen concentration (SUN), decrease in food intake, and a zone of proximal tubular cell necrosis in the inner cortex. By day 3 low cuboidal epithelial cells were seen, indicating that regeneration had been initiated despite decreased food intake and increasing SUN. Phospholipid synthesis for new membrane formation in regenerating cells was studied by using [14C] choline as a precursor of phosphorylcholine and cytidine diphosphocholine (CDP-choline), which are intermediates in the synthesis of renal choline-containing phospholipid. The rate of [14C]choline incorporation into phospholipids in inner cortical slices was lowest 1 day after mercury administration, then increased constantly for the next 4 days to reach a maximal value 104% above control. The rate declined slowly for the next 11 days and returned to normal by 28 days. The increased rate represented choline phosphoglyceride synthesis, since degradation was unchanged. The entire increment in choline radioactivity in regenerating tissue 2 and 3 days after mercury administration was in phospholipid or CDP-choline, which suggests that the increased number of choline molecules entering the growing cells were trapped in these two forms. The results indicate that renal regeneration is associated with a specific enhancement of the synthesis of choline-containing phospholipids. This anabolic response of the kidney occurs in the presence of systemic catabolism and progressive renal functional insufficiency.