Hedgepeth R C, Yang L, Resnick M I, Marengo S R
Department of Urology, James and Eilleen Dicke Research Laboratory, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4931, USA.
Am J Kidney Dis. 2001 Jan;37(1):104-112. doi: 10.1053/ajkd.2001.20594.
The factors precipitating clinically active calcium oxalate (CaOx) urolithiasis are not known. This study examined the relationships between urinary proteins that inhibit CaOx crystallization in vitro and the incidence of CaOx urolithiasis. The first hypothesis is that levels of urinary CaOx crystallization inhibitors differ between clinically active stone formers (SFs) and normal individuals. The second hypothesis is that lower levels of urinary CaOx crystallization inhibitors contribute to the two- to threefold greater incidence of CaOx urolithiasis in males compared with females. These hypotheses were derived from previous observations on the expression of urinary inter-alpha-trypsin inhibitor trimer (IalphaTI-trimer) in normal and stone-forming individuals. The proteins of void urine samples from normal volunteers (24 males, 19 females) and CaOx-SFs (26 males, 16 females) were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoreactive IalphaTI-trimer, osteopontin, and prothrombin were detected by immunoblot plus enhanced chemiluminescence; the relative densities of the bands were then determined. With the exception of IalphaTI-trimer (P: </= 0.026, approximately twofold), there was no difference in the relative densities of CaOx crystallization inhibitors in the urine of normal and CaOx stone-forming individuals. Thus, there does not appear to be a generalized increase or decrease in levels of CaOx crystallization inhibitory proteins between normal and CaOx stone-forming individuals. The relative density of IalphaTI-trimer was approximately threefold greater in females than in males (P: </= 0.001). Differences in the relative densities of the other CaOx crystallization inhibitors were small and of questionable physiological importance. These data do not support the hypothesis that males have a greater incidence of CaOx urolithiasis because of a generalized decrease in urinary CaOx crystallization inhibitory protein levels.
引发临床活动性草酸钙（CaOx）尿石症的因素尚不清楚。本研究检测了体外抑制CaOx结晶的尿蛋白与CaOx尿石症发病率之间的关系。第一个假设是，临床活动性结石形成者（SFs）与正常个体之间尿CaOx结晶抑制剂的水平存在差异。第二个假设是，尿CaOx结晶抑制剂水平较低导致男性CaOx尿石症发病率比女性高两到三倍。这些假设源于之前对正常人和结石形成者尿液中α-胰蛋白酶抑制剂三聚体（IαTI-三聚体）表达的观察。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分离正常志愿者（24名男性，19名女性）和CaOx-SFs（26名男性，16名女性）的空腹尿样蛋白。通过免疫印迹加增强化学发光检测免疫反应性IαTI-三聚体、骨桥蛋白和凝血酶原；然后测定条带的相对密度。除IαTI-三聚体（P≤0.026，约两倍）外，正常人和CaOx结石形成者尿液中CaOx结晶抑制剂的相对密度没有差异。因此，正常人和CaOx结石形成者之间CaOx结晶抑制蛋白水平似乎没有普遍升高或降低。女性IαTI-三聚体的相对密度比男性大约高三倍（P≤0.001）。其他CaOx结晶抑制剂相对密度的差异很小，生理重要性存疑。这些数据不支持男性CaOx尿石症发病率较高是由于尿CaOx结晶抑制蛋白水平普遍降低这一假设。
