Hatch Marguerite, Freel Robert W
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Fla 32610, USA.
Am J Nephrol. 2003 Jan-Feb;23(1):18-26. doi: 10.1159/000066300.
The enteric excretion of oxalate has been established in rats with chronic renal failure induced by 5/6 nephrectomy [Hatch et al.: Regulatory aspects of oxalate secretion in enteric oxalate elimination. JASN 1999;10:S324] and this response is mediated by angiotensin II receptor activation. However, the renal and intestinal handling of oxalate has not been evaluated for other common models of hyperoxaluria that simulate primary hyperoxaluria or oxalate stone disease.
We assessed the renal clearances of creatinine, oxalate and calcium in three rat models: chronic hyperoxaluria (CH), chronic hyperoxaluria with hyperoxalemia (CHH) and acute hyperoxaluria (AH), and evaluated the transepithelial transport of oxalate and chloride in large intestinal segments of these models and their sensitivity to angiotensin II antagonism.
Hyperoxaluria alone (CH) was not associated with changes in colonic oxalate transport, whereas changes in net oxalate transport in distal colon from absorption to net secretion was observed in models with hyperoxalemia (CHH and AH). Angiotensin II receptor antagonism with losartan reduced net colonic oxalate secretion in AH but not CHH.
Colonic secretion of oxalate is stimulated in rat models exhibiting hyperoxalemia suggesting a contribution of this extrarenal pathway to regulation of oxalate mass balance in clinical conditions manifesting hyperoxalemia. The transport avenues and regulatory mechanisms may not be identical to those observed during adaptive enteric oxalate secretion in chronic renal failure models.
5/6肾切除诱导的慢性肾衰竭大鼠中已证实草酸盐经肠道排泄[哈奇等人：肠道草酸盐清除中草酸盐分泌的调节方面。《美国肾脏病学会杂志》1999年；10：S324]，且该反应由血管紧张素II受体激活介导。然而，对于模拟原发性高草酸尿症或草酸盐结石病的其他常见高草酸尿症模型，尚未评估肾脏和肠道对草酸盐的处理情况。
我们评估了三种大鼠模型中肌酐、草酸盐和钙的肾清除率：慢性高草酸尿症（CH）、伴有高草酸血症的慢性高草酸尿症（CHH）和急性高草酸尿症（AH），并评估了这些模型大肠段中草酸盐和氯离子的跨上皮转运及其对血管紧张素II拮抗作用的敏感性。
单纯高草酸尿症（CH）与结肠草酸盐转运变化无关，而在伴有高草酸血症的模型（CHH和AH）中，观察到远端结肠净草酸盐转运从吸收变为净分泌的变化。用氯沙坦进行血管紧张素II受体拮抗可降低AH模型中结肠草酸盐的净分泌，但对CHH模型无效。
在表现出高草酸血症的大鼠模型中，结肠草酸盐分泌受到刺激，这表明在临床高草酸血症情况下，这种肾外途径对草酸盐质量平衡的调节有贡献。其转运途径和调节机制可能与慢性肾衰竭模型中适应性肠道草酸盐分泌时观察到的不同。
