Metabolism in the Hypothermically Perfused Kidney: Utilization of in;Mevalonate i -he Human anthe Dog Kidney

Abstract

The metabolism of mevalonate was studied in 6 dog kidneys and in 5 human tumour-involved kidneys during 6 days of hypothermic perfusion. ¹⁴C-mevalonate in the perfusate decreased and was incorporated into the total lipid fraction of the cortex in both human and dog kidneys. 80 % of the incorporated radioactivity was found in the non-saponifiable lipids and after separation of that lipid fraction the radioactivity was recovered in cholesterol as well as in the cholesterol precursors lanosterol and squalene. Only very low levels of radioactivity were recovered in the tumour lipids. It is concluded that the kidney utilizes mevalonate for cholesterol synthesis during hypothermic perfusion and that addition of mevalonate may be of importance for preserving the membrane stability. Furthermore, it is suggested that hypothermic perfusion has a more deteriorating effect on the viability of the tumour tissue when compared to normal renal parenchyma.

NOS: The Underlying Mechanism Preserving Vascular Integrity and During Ex Vivo Warm Kidney Perfusion

“…Likewise, the canine kidney model has also been instrumental in the development of supporting preservation technologies such as perfusion preservation, static storage and in establishing their relative efficacy (37)(38)(39). The canine kidney model has also been employed to assess immunologic complications and injury following preservation, potential pharmacologic interventions and substrate requirements (40)(41)(42)(43)(44)(45)(46)(47)(48).…”

Current Insights into the Metabolome during Hypothermic Kidney Perfusion—A Scoping Review

“…When a fatty acid-rich perfusate was used, phospholipid levels did not change [49] or decreased [48]. Tissue cholesterol levels remained unchanged in three studies in which kidneys were pumped for 2 to 6 days [47,49,53] and decreased in one study after 6 days of perfusion [48].…”

“…In these studies, a mixture of O 2 and CO 2 [17,[19][20][21][22]25,34,[40][41][42][43][44][45] or a mixture of O 2 , CO 2 , and nitrogen [26,27,38,[46][47][48][49] was given. Surface oxygenation with room air or O 2 (13/40; 33%) [20,32,37,38,[41][42][43][50][51][52][53][54][55] was also used. In one article (3%), bubble and surface oxygenation were combined [20].…”

“…Details are listed in Tables 2 and S8. In nine studies, radioactively labeled metabolites-also called tracers-were added to the perfusion circuit to investigate active metabolic pathways: 14 C-glucose [27,42,[46][47][48], 14 C-mevalonate [53], 14 C-acetate [47], 14 C-lactate [47], 14 C-labeled amino acids ( 14 Ccycloleucine [42], 14 C-leucine [41], 14 C-threonine [41]), 14 C-labeled fatty acids ( 14 C-linoleate [46,48,49], 14 C-palmitate [26,46,48,49], 14 C-caprylate [42,46,48], 14 C-myristic acid [48]).…”