Post-ischemic acute renal failure protects proximal tubules from O2 deprivation injury, possibly by inducing uremia

Abstract

Rats within the early maintenance phase of post-ischemic acute renal failure (ARF) can resist additional ischemic insults. This study assessed whether this protection exists directly at the tubular cell level, and if so, whether it is a consequence of prior cell injury (for example, due to heat-shock protein synthesis; HSP), or if it arises in response to reductions in functional renal mass and/or the uremic environment. Rats were subjected to either 15 or 35 minutes of unilateral or bilateral renal ischemia, and after 15 minutes to 24 hours of reflow, proximal tubular segments (PTS) were isolated for study. Their viability following oxygenation and hypoxic/reoxygenation injury (H/R) was tested (LDH release). The influence of uremia/reduced renal mass was determined by studying PTS extracted 24 hours after 1 1/2 nephrectomy, and by determining whether PTS exposure to a "uremic milieu" (urine addition) blocks H/R damage. HSP effects were gauged by correlating renal cortical HSP-70 expression with degrees of in vitro protection, and by ascertaining whether in vivo hyperthermia (42 degrees C; 15 min) mitigates subsequent PTS H/R damage. Results were compared with those obtained from normal PTS. The in vivo experimental protocols did not substantially alter PTS isolation or their viability during oxygenation. Fifteen minutes of ischemia induced neither azotemia nor PTS cytoprotection. In contrast, 35 minutes of ischemia conferred marked protection against subsequent H/R, but only when azotemia was permitted to develop (protection seen after 24 hr, but not at 4 hr of reflow; protection abrogated by retention of 1 normal kidney). Renal failure in the absence of tubular necrosis (1 1/2 uninephrectomy) protected PTS from H/R damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental Glomerulopathy Alters Renal Cortical Cholesterol, SR-B1, ABCA1, and HMG CoA Reductase Expression

“…5,37 Probing for HMGCR and HSP-72 used methodologies and reagents as previously reported. 5,36,37 In the case of SR-B1, 7 g of protein extract were electrophoresed into a 12% Bis-Tris acrylamide gel (Invitrogen, Carlsbad, CA) and probed with rabbit anti-SR-B1 antibody (catalogue number NB-400-104; Novus Biologicals, Littleton, CO). For ABCA1 detection, 30 g of protein was electrophoresed into a 4 to 12% gradient Bis-Tris acrylamide gel (Invitrogen).…”

“…They were then used for either glomerular isolation by a previously reported sieving technique (n ϭ 6 PHN and 6 control rats), 30 or for isolated PTS collection (n ϭ 4 PHN and 4 controls), as previously described in detail. 35,36 The isolated tubules and glomeruli were subjected to lipid extraction, followed by FC and CE analysis, as noted above.…”

Inducible Nitric-oxide Synthase Is an Important Contributor to Prolonged Protective Effects of Ischemic Preconditioning in the Mouse Kidney

“…Ischemic preconditioning is the phenomenon whereby a prior ischemic stress renders the organ resistant to a subsequent ischemic insult (1)(2)(3)(4). In the heart preconditioning, induced by short episodes of ischemia and reperfusion treatment, has two distinct phases: an early phase that lasts from a few minutes to 2 or 3 h and a late phase that is sustained for 2-4 days (5).…”

Aberrant Tubuloglomerular Feedback and HIF-1α Confer Resistance to Ischemia after Subtotal Nephrectomy

“…29 These studies include preconditioning by a prior ischemic insult, ureteral obstruction, nephrotoxic antiserum, gentamicin exposure, pretreatment with sodium arsenite, repeat exposure to uranium and/or single exposure after nephritis, repeat exposure to glycerol, and protection against mercuric chloride in animals with prior glycerol nephrotoxicity and vice versa. [41][42][43][44][45][46][47][48][49][50][51][52] Another limitation is that the STN model does not capture etiological or phenotypical features of kidney disease, but it does recapitulate the consequences of nephron reduction common to nearly all forms of kidney disease. Similar findings have been observed in different strains of rats and at different time points after STN.…”