Baum M
Department of Pediatrics and Internal Medicine, University of Texas Southwestern Medical School, Dallas 75235-9063, USA.
Pediatr Nephrol. 1998 Aug;12(6):492-7. doi: 10.1007/s004670050495.
Cystinosis is a lysosomal storage disease which is the most-common inherited cause of the Fanconi syndrome. Insights into the pathophysiology of the proximal tubular defect have come from in vitro studies of the cystine-loaded tubule. Proximal tubules loaded with cystine have a generalized proximal tubule transport defect characteristic of the Fanconi syndrome. The decrease in proximal tubular transport with cystine loading is not due to an increase in paracellular permeability with backflux of solute transport from the blood to the tubular lumen, but due to a decrease in active transport. The Na-K-ATPase activity is intact under Vmax conditions in cystine-loaded tubules; however, the production of ATP is severely compromised. The cystine-loaded tubule has a lower intracellular phosphate concentration than that of control tubules. This low intracellular phosphate concentration in cystine-loaded tubules likely plays a critical role in the decrease in intracellular ATP. Preservation of intracellular phosphate at control levels prevents the decrease in intracellular ATP and the proximal tubule respiratory dysfunction with cystine loading. The clinical significance and future directions for investigation are discussed.
胱氨酸贮积症是一种溶酶体贮积病，是范科尼综合征最常见的遗传病因。对近端肾小管缺陷病理生理学的深入了解来自对胱氨酸负荷肾小管的体外研究。加载胱氨酸的近端肾小管具有范科尼综合征特征性的广泛性近端肾小管转运缺陷。加载胱氨酸时近端肾小管转运的减少并非由于细胞旁通透性增加以及溶质从血液反流至肾小管管腔，而是由于主动转运减少。在最大反应速度条件下，加载胱氨酸的肾小管中钠钾ATP酶活性完好；然而，ATP的产生严重受损。加载胱氨酸的肾小管细胞内磷酸盐浓度低于对照肾小管。加载胱氨酸的肾小管中这种低细胞内磷酸盐浓度可能在细胞内ATP减少中起关键作用。将细胞内磷酸盐维持在对照水平可防止加载胱氨酸时细胞内ATP减少以及近端肾小管呼吸功能障碍。文中讨论了其临床意义和未来的研究方向。
