Oleic acid loading does not add to the nephrotoxic effect of albumin in an amphibian and chronic rat model of kidney injury

Background. Under proteinuric conditions, ultrafiltrated albumin can induce an inflammatory and fibrotic response in proximal tubular cells. It is unclear whether albumin per se or compounds bound to albumin are nephrotoxic. Some studies have supported the toxicity of albumin-bound fatty acids; however, these compared untreated, fatty acid containing, albumin and delipidated albumin. To prevent confounding by the delipidation procedure, we compared delipidated albumin and oleic acid (OA)-loaded delipidated albumin in two models: the classical rat protein overload and the Axolotl. The latter had an amphibian kidney with a subset of nephrons that drained the peritoneal cavity, so that i.p. injection of albumin selectively targeted open but not closed nephrons and was used to prevent removal of fatty acids from albumin in the circulation. Methods. Protein overload was induced in Wistar rats (groups n = 8, for 12 weeks) and Axolotl (groups n = 10, for 10 days) by daily i.p. injections of 1 g (rat) or 50 mg (Axolotl) of fatty acid-free bovine serum albumin (BSA), fatty acid-free BSA with addition of six molecules of oleic acid (OA-BSA) or saline (SAL). Results. After 12 weeks, proteinuria and SBP were increased in BSA and OA-BSA rats compared to saline-injected controls (P