Wagner Carsten A
Institute of Physiology and Zurich Center for Human Integrative Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
Curr Opin Nephrol Hypertens. 2007 Sep;16(5):471-6. doi: 10.1097/MNH.0b013e3282a4a69c.
Metabolic acidosis is a severe disturbance of extracellular pH homeostasis that can be caused both by inborn or acquired defects in renal acid excretion or metabolic acid production. Chronic metabolic acidosis causes osteomalacia with nephrocalcinosis and urolithiasis. In the setting of end-stage renal disease, metabolic acidosis is often associated with increased peripheral insulin resistance, and represents an additional independent morbidity risk factor. This review summarizes recent insight, gained primarily from mouse models, into the mechanisms whereby the kidney regulates and adapts acid excretion.
Human genetics and various mouse models have shed new light on mechanisms that contribute to the kidney's ability to excrete acid and adapt appropriately to metabolism. Progress in four specific areas will be highlighted: mechanisms contributing to the synthesis and excretion of ammonia; insights into adaptive processes during acidosis; mechanisms by which the kidney may sense acidosis; and the pathophysiology of acquired and inborn errors of renal acid handling.
Genetic mouse models and various messenger RNA and proteome profiling and screening technologies demonstrate the importance of various acid-base transporting proteins and a metabolic and regulatory network that contributes to the kidney's ability to maintain the systemic acid-base balance.
代谢性酸中毒是细胞外pH稳态的严重紊乱，可由先天性或后天性肾酸排泄缺陷或代谢性酸生成异常引起。慢性代谢性酸中毒会导致骨软化症并伴有肾钙质沉着症和尿路结石。在终末期肾病的情况下，代谢性酸中毒常与外周胰岛素抵抗增加相关，是一个额外的独立发病风险因素。本综述总结了主要从小鼠模型中获得的关于肾脏调节和适应酸排泄机制的最新见解。
人类遗传学和各种小鼠模型为有助于肾脏排泄酸并适当适应代谢的机制提供了新的线索。将重点介绍四个特定领域的进展：氨合成和排泄的机制；酸中毒期间适应性过程的见解；肾脏感知酸中毒的机制；以及获得性和先天性肾酸处理异常的病理生理学。
基因小鼠模型以及各种信使核糖核酸和蛋白质组分析与筛选技术证明了各种酸碱转运蛋白以及有助于肾脏维持全身酸碱平衡能力的代谢和调节网络的重要性。
