Renal microcirculation and tissue damage during acute ureteral obstruction in the rat: effect of saline infusion, indomethacin and radiocontrast.
Radiocontrast agents and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the diagnosis and treatment of renal colic. We studied their impact during unilateral acute urinary outflow obstruction upon renal microcirculation and parenchymal integrity. Laser-Doppler and ultrasonic regional flow measurements demonstrated selective decline of outer medullary blood flow by 23 +/- 2% during an acute increase of intra-pelvic pressure to 50 to 55 cm H2O (N = 28, X +/- SEM, P < 0.01). In rats preconditioned with indomethacin, this manipulation reduced medullary blood flow by 50 +/- 4% (N = 16, P < 0.01 vs. obstruction alone), with cortical and total renal blood flow declining by 18 +/- 4% and 16 +/- 2%, respectively (P < 0.01). Unilateral obstruction alone for 24 hours in intact rats resulted in injury (hemorrhage and necrosis) to the papilla and fornix (formed laterally by inner stripe and medially by the inner medulla). These changes were detected as early as 30 minutes after ureteral ligature by staining for fragmented nuclear DNA (TUNEL). Mild damage of thick ascending limbs (mTALs) was associated with substantial medial fornix injury. Indomethacin markedly increased mTAL injury in obstructed kidneys, but attenuated inner medullary damage, both in the medial border of the urinary space and at the papilla. This latter protective effect, probably mediated by the decrease in intrapelvic pressure, was blunted by concomitant intravenous fluid load. Contrast media (iothalamate) and L-NAME (N omega nitro-L-arginine methyl ester) both augmented inner stripe and inner medullary damage in hydronephrotic kidneys. In rats concomitantly subjected to radiocontrast, indomethacin and L-NAME (an acute renal failure protocol, J Clin Invest 94:1069, 1994), unilateral obstruction augmented inner stripe hypoxic damage (65 +/- 6% vs. 24 +/- 11% of mTALs in contralateral kidneys, N = 7, P < 0.01). Injury was maximal at the fornix (93 +/- 6% vs. 39 +/- 14% of mTALs in the mid-inner stripe, P < 0.01) and extended to the outer stripe and medullary rays. Thus, in the rat acute ureteral obstruction alters medullary blood flow and within 24 hours produces medullary damage in both forniceal and inner medullary locations, that is exacerbated by concomitant measures which limit medullary oxygenation. Contrast studies, forced hydration and NSAIDs for renal colic are potentially harmful and their use should be re-evaluated.
Heyman
S N
SN
Department of Medicine, Hadassah Hospital, Mt. Scopus, Jerusalem, Israel. Heyman@yam-suff.cc.huji.ac.il
Fuchs
S
S
Jaffe
R
R
Shina
A
A
Ellezian
L
L
Brezis
M
M
Rosen
S
S
D000208:Acute Disease; D000818:Animals; D003287:Contrast Media / Q000633:toxicity; D053938:DNA Fragmentation; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin / Q000633:toxicity; D007483:Iothalamic Acid / Q000633:toxicity; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D008854:Microscopy, Electron; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000473:pathology* / Q000503:physiopathology*
D003287:Contrast Media; D007483:Iothalamic Acid; D012965:Sodium Chloride; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin