Temperature effects on ischemic and hypoxic renal proximal tubular injury.
Body temperature (T) profoundly alters the severity of ischemic acute renal failure. Therefore, the present study evaluated T effects on: (a) in vitro proximal tubular cell killing during hypoxia/reoxygenation to assess when it exacerbates injury; (b) renal ATP losses and metabolic rate (O2 consumption) during hemorrhagic shock (55-60 mm Hg); and (c) membrane deacylation (assessed by free fatty acid, FFA, release) to determine if T modifies this pathway of ischemic renal damage. Hypoxic cell kill (45 minutes) was 20 +/- 1% 47 +/- 4%, and 61 +/- 2% at 32 degrees C, 37 degrees C, and 40 degrees C respectively (by lactate dehydrogenase release; p less than 0.001). During reoxygenation (15 minutes), minimal lactate dehydrogenase was released, irrespective of T. ATP decrements during shock were profoundly T dependent (% loss of ATP; 15%, 30%, 58% at 32.5 degrees C, 37 degrees C, and 39.5 degrees C, respectively; p less than 0.001), reflecting T-dependent increments in renal metabolic rate, not decreased O2 delivery (arterial O2 content; renal blood flow). ATP losses during shock correlated with the extent of S3 proximal tubular morphologic damage. O2 deprivation dramatically increased FFA levels both in vivo and in vitro but the increments were only slightly T dependent. In vitro, % lactate dehydrogenase release and FFA levels did not significantly correlate and bovine serum albumin, a FFA binder, conferred no protection.


CONCLUSIONS
(a) T dramatically accentuates hypoxic, not reoxygenation, injury; (b) changes in membrane deacylation do not appear to underlie this effect; and (c) T has a profound impact on renal ATP losses during shock, thereby affecting the severity of ischemic renal damage.
Zager
R A
RA
Department of Medicine, University of Washington, Seattle.
Gmur
D J
DJ
Bredl
C R
CR
Eng
M J
MJ
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001831:Body Temperature; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005260:Female; D000860:Hypoxia / Q000473:pathology*; D007511:Ischemia / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D010101:Oxygen Consumption; D051381:Rats; D012078:Renal Artery Obstruction / Q000097:blood; D012079:Renal Circulation; D012769:Shock / Q000378:metabolism / Q000473:pathology
D000227:Adenine Nucleotides; D005227:Fatty Acids; D000255:Adenosine Triphosphate