Lefkowith J B, Pippin J, Nagamatsu T, Lee V
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
J Am Soc Nephrol. 1992 May;2(11):1560-7. doi: 10.1681/ASN.V2111560.
Nephrotoxic nephritis, a model system for glomerulonephritis, is characterized by glomerular inflammation, proteinuria, and a marked increase in ex vivo glomerular eicosanoid production. This study addressed whether urinary eicosanoids might serve as noninvasive markers for glomerular inflammation and damage with nephrotoxic nephritis and its accelerated variant. Accelerated nephritis, relative to simple nephritis, was characterized by more substantial glomerular inflammation, particularly that due to neutrophils. Correspondingly, accelerated nephritis was accompanied by greater proteinuria and more marked elevations in glomerular eicosanoids generated ex vivo. With respect to urinary eicosanoids, thromboxane, but not leukotriene B4, was detected in the urine of normal animals. After the induction of nephrotoxic nephritis, urinary thromboxane was moderately elevated (twofold) and urinary leukotriene B4 was variably present (three of seven animals). In accelerated nephritis, urinary thromboxane was more markedly elevated (sixfold) and leukotriene B4 was consistently present. The presence of urinary leukotriene B4 was confirmed by gas chromatography/mass spectrometry. Urinary eicosanoids together correlated with glomerular leukocyte numbers and proteinuria by linear regression. Urinary leukotriene B4 individually correlated with glomerular neutrophil numbers. Renal metabolism of leukotriene B4 to omega oxidation products by the rat kidney was not apparent. These data validate that the enhanced glomerular eicosanoid metabolism seen in nephrotoxic nephritis takes place in vivo and additionally suggest that both urinary thromboxane and leukotriene B4 may serve as noninvasive markers for glomerular inflammation and damage. In light of these and prior studies, urinary thromboxane may be a general marker of glomerular inflammation and leukotriene B4 may be a more specific index of acute inflammation.
肾毒性肾炎是一种肾小球肾炎的模型系统，其特征为肾小球炎症、蛋白尿以及体外肾小球类花生酸生成显著增加。本研究探讨了尿类花生酸是否可作为肾毒性肾炎及其加速型变体中肾小球炎症和损伤的非侵入性标志物。与单纯性肾炎相比，加速性肾炎的特征是肾小球炎症更严重，尤其是由中性粒细胞引起的炎症。相应地，加速性肾炎伴有更大量的蛋白尿以及体外生成的肾小球类花生酸更显著升高。关于尿类花生酸，正常动物尿液中可检测到血栓素，但未检测到白三烯B4。诱导肾毒性肾炎后，尿血栓素中度升高（两倍），尿白三烯B4有变化地出现（七只动物中有三只）。在加速性肾炎中，尿血栓素升高更显著（六倍），白三烯B4持续存在。气相色谱/质谱法证实了尿白三烯B4的存在。尿类花生酸通过线性回归与肾小球白细胞数量和蛋白尿相关。尿白三烯B4单独与肾小球中性粒细胞数量相关。大鼠肾脏将白三烯B4代谢为ω氧化产物的情况不明显。这些数据证实，肾毒性肾炎中增强的肾小球类花生酸代谢发生在体内，此外还表明尿血栓素和白三烯B4均可作为肾小球炎症和损伤的非侵入性标志物。鉴于这些研究及先前的研究，尿血栓素可能是肾小球炎症的一般标志物，而白三烯B4可能是急性炎症更特异的指标。
