Heyman S N, Fuchs S, Jaffe R, Shina A, Ellezian L, Brezis M, Rosen S
Department of Medicine, Hadassah Hospital, Mt. Scopus, Jerusalem, Israel.
Kidney Int. 1997 Mar;51(3):653-63. doi: 10.1038/ki.1997.95.
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.
放射造影剂和非甾体抗炎药（NSAIDs）常用于肾绞痛的诊断和治疗。我们研究了它们在单侧急性尿路梗阻期间对肾微循环和实质完整性的影响。激光多普勒和超声区域血流测量显示，当肾盂内压力急性升高至50至55 cm H2O时，外髓质血流选择性下降23±2%（N = 28，X±SEM，P < 0.01）。在预先用吲哚美辛预处理的大鼠中，这种操作使髓质血流减少50±4%（N = 16，与单纯梗阻相比P < 0.01），皮质和总肾血流分别下降18±4%和16±2%（P < 0.01）。在完整大鼠中单独进行单侧梗阻24小时导致乳头和穹窿（外侧由内带形成，内侧由内髓质形成）损伤（出血和坏死）。通过对片段化核DNA进行染色（TUNEL），早在输尿管结扎后30分钟就检测到了这些变化。厚升支（mTALs）的轻度损伤与明显的内侧穹窿损伤相关。吲哚美辛显著增加梗阻肾脏中的mTAL损伤，但减轻了肾盂内空间内侧边界和乳头处的内髓质损伤。后一种保护作用可能由肾盂内压力降低介导，静脉补液会减弱这种作用。造影剂（碘他拉酸盐）和L - NAME（Nω - 硝基 - L - 精氨酸甲酯）都加重了肾积水肾脏的内带和内髓质损伤。在同时接受放射造影剂、吲哚美辛和L - NAME的大鼠中（一种急性肾衰竭方案，《临床研究杂志》94:1069，1994），单侧梗阻加重了内带缺氧损伤（与对侧肾脏中mTALs的24±11%相比为65±6%，N = 7，P < 0.01）。损伤在穹窿处最为严重（与内带中部mTALs的39±14%相比为93±6%，P < 0.01），并扩展到外带和髓放线。因此，在大鼠中，急性输尿管梗阻会改变髓质血流，并在24小时内在穹窿和内髓质部位产生髓质损伤，同时采取的限制髓质氧合的措施会加剧这种损伤。造影剂研究、强制水化和用于肾绞痛的NSAIDs可能有害，其使用应重新评估。
