Hatch Marguerite, Freel Robert W
Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100275, Gainesville, FL 32610, USA.
Urol Res. 2003 Dec;31(6):426-32. doi: 10.1007/s00240-003-0367-5. Epub 2003 Oct 22.
Enteric secretion of oxalate is induced in rats that have chronic renal failure produced by 5/6 nephrectomy. The purpose of the present study was to examine renal and intestinal handling of oxalate in rats with chronic renal failure (CRF) induced by chronic hyperoxaluria. A rat model for chronic renal failure, induced by chronic hyperoxaluria (CH-CRF), was produced by unilateral nephrectomy combined with dietary ethylene glycol for 4 weeks. Both intact and unilateral nephrectomized rats (UN) without the oxalate load served as controls. Renal handling of oxalate was assessed by measurement of renal clearance of oxalate and creatinine while colonic handling of oxalate and chloride was determined by in vitro transepithelial flux measurements. Angiotensin II mediation was assessed by sensitivity of the transport processes to the AT(1) receptor antagonist losartan. Renal and colonic handling of oxalate in UN rats were similar to intact controls. The CH-CRF rats were hyperoxalemic, hyperoxaluric, and exhibited a twofold increase in oxalate clearance despite a 50% drop in creatinine clearance. Distal (but not proximal) colonic handling of oxalate in CH-CRF rats was reversed from net oxalate absorption seen in UN and intact controls to net secretion that was sensitive to losartan in vitro.
Although enteric oxalate secretion can be correlated with elevations in plasma oxalate in the absence of overt renal insufficiency by an ANG II-independent mechanism, the present results suggest that some degree of renal insufficiency is necessary to induce ANG II-mediated colonic oxalate secretion.
5/6肾切除所致慢性肾衰竭大鼠会出现肠道草酸盐分泌。本研究旨在探讨慢性高草酸尿症诱导的慢性肾衰竭（CRF）大鼠的肾脏和肠道对草酸盐的处理情况。通过单侧肾切除联合给予乙二醇饮食4周建立慢性高草酸尿症诱导的慢性肾衰竭大鼠模型（CH-CRF）。未负荷草酸盐的完整大鼠和单侧肾切除大鼠（UN）作为对照。通过测量草酸盐和肌酐的肾清除率评估肾脏对草酸盐的处理，通过体外跨上皮通量测量确定结肠对草酸盐和氯离子的处理。通过转运过程对AT(1)受体拮抗剂氯沙坦的敏感性评估血管紧张素II的介导作用。UN大鼠的肾脏和结肠对草酸盐的处理与完整对照相似。CH-CRF大鼠出现高草酸血症、高草酸尿症，尽管肌酐清除率下降50%，但其草酸盐清除率仍增加两倍。CH-CRF大鼠远端（而非近端）结肠对草酸盐的处理从UN大鼠和完整对照中的草酸盐净吸收转变为体外对氯沙坦敏感的净分泌。
尽管在无明显肾功能不全时，肠道草酸盐分泌可通过非血管紧张素II依赖机制与血浆草酸盐升高相关，但目前结果表明，一定程度的肾功能不全对于诱导血管紧张素II介导的结肠草酸盐分泌是必要的。
