POSTISCHEMIC ACUTE-RENAL-FAILURE PROTECTS PROXIMAL TUBULES FROM O-2 DEPRIVATION INJURY, POSSIBLY BY INDUCING UREMIA

Rats within the early maintenance phase of post-ischemic acute renal f ailure (ARF) can resist additional ischemic insults. This study assess ed whether this protection exists directly at the tubular cell level, and if so, whether it is a consequence of prior cell injury (for examp le, due to heat-shock protein synthesis; HSP), or if it arises in resp onse to reductions in functional renal mass and/or the uremic environm ent. Rats were subjected to either 15 or 35 minutes of unilateral or b ilateral renal ischemia, and after 15 minutes to 24 hours of reflow, p roximal tubular segments (PTS) were isolated for study. Their viabilit y following oxygenation and hypoxic/reoxygenation injury (HIR) was tes ted (LDH release). The influence of uremia/reduced renal mass was dete rmined by studying PTS extracted 24 hours after 1 1/2 nephrectomy, and by determining whether PTS exposure to a ''uremic milieu'' (urine add ition) blocks H/R damage. HSP effects were gauged by correlating renal cortical HSP-70 expression with degrees of in vitro protection, and b y ascertaining whether in vivo hyperthermia (42 degrees C; 15 min) mit igates subsequent PTS H/R damage. Results were compared with those obt ained from normal PTS. The in vivo experimental protocols did not subs tantially alter PTS isolation or their viability during oxygenation. F ifteen minutes of ischemia induced neither azotemia nor PTS cytoprotec tion. In contrast, 35 minutes of ischemia conferred marked protection against subsequent H/R, but only when azotemia was permitted to develo p (protection seen after 24 hr, but not at 4 hr of reflow; protection abrogated by retention of 1 normal kidney). Renal failure in the absen ce of tubular necrosis (1 1/2 uninephrectomy) protected PTS from HIR d amage. Adding urine directly to PTS also lessened HIR injury, independ ent of pH or osmotic effects. Post-ischemic HSP synthesis correlated p oorly with cytoresistance, and hyperthermia-induced HSP expression exe rted only a trivial protective effect. These results indicate that: (a ) post-ischemic ARF directly protects tubular cells against subsequent O-2 deprivation injury; and (b) this appears to result not from cell injury per se, but rather, by exposure to a uremic environment.