Caudarella Renata, Vescini Fabio
Centro Studi del Metabolismo Minerale, Fondazione Villa Maria, Lugo, Ravenna, Italy.
Arch Ital Urol Androl. 2009 Sep;81(3):182-7.
Hypocitraturia or low urinary citrate excretion is a common feature in patients with nephrolithiasis, particularly in those with calcium stone disease. Citrate is a weak acid that is synthesized inside Krebs' cycle. It can also enter the body through dietary intake. Differences in intestinal handling, serum concentration as well as filtered load of citrate were not found between kidney stone formers and normal subjects. On the contrary, several metabolic abnormalities, such as metabolic acidosis, hypokalemia and starving, seem to influence the renal handling of citrate by inducing a decrease in the urinary citrate excretion. Hypocitraturia is defined as urinary citrate excretion lower than 320 mg/day. Literature data show a large prevalence of hypocitraturia in patients with nephrolithiasis, ranging from 8% up to 68.3%. The protective role of citrate is linked to several mechanisms; in fact citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Furthermore, citrate increases the activity of some macromolecules in the urine (eg. Tamm-Horsfall protein) that inhibit calcium oxalate aggregation. Citrate seems able to reduce the expression of urinary osteopontin. A role of citrate in pathogenesis of metabolic bone diseases has been recently suggested and citrate measurement in urine has been proposed as a predictor of both bone mass loss and fracture risk. Idiopathic calcium stone disease, with or without hypocitraturia, can be treated with alkaline citrate, as well as other forms of nephrolithiasis and different pathological conditions. The therapy with potassium citrate, or magnesium potassium citrate, is commonly prescribed in clinical practice in order to increase urinary citrate and to reduce stone formation rates. Our data as well as those of the literature confirm that alkali citrate induces both an increase of protective urinay analytes (eg. citrate, potassium and pH) and a decrease of calcium oxalate supersaturation. Moreover, alkali treatment reduces the rate of stone recurrence and increases the clearance rates and dissolution of stone fragments. Last but not the least, an increasing number of papers pointed out the protective role of alkali citrate in preserving bone mass in stone formers as well as in healthy subjects with bone loss. Nevertheless, the evaluation of urinary citrate in patients with kidney stones and the treatment of these patients with alkali salts namely with potassium citrate are still scarce.
低枸橼酸尿症或尿枸橼酸盐排泄减少是肾结石患者的常见特征，尤其是在患有钙结石病的患者中。枸橼酸盐是一种在三羧酸循环中合成的弱酸。它也可以通过饮食摄入进入人体。肾结石患者与正常受试者在肠道处理、血清浓度以及枸橼酸盐滤过量方面未发现差异。相反，一些代谢异常，如代谢性酸中毒、低钾血症和饥饿，似乎通过导致尿枸橼酸盐排泄减少来影响肾脏对枸橼酸盐的处理。低枸橼酸尿症定义为尿枸橼酸盐排泄低于320毫克/天。文献数据显示，肾结石患者中低枸橼酸尿症的患病率很高，范围从8%到68.3%。枸橼酸盐的保护作用与多种机制有关；事实上，枸橼酸盐通过与钙离子形成可溶性复合物以及抑制晶体生长和聚集来降低钙盐的尿饱和度。此外，枸橼酸盐增加尿液中一些大分子（如Tamm-Horsfall蛋白）的活性，这些大分子抑制草酸钙聚集。枸橼酸盐似乎能够降低尿骨桥蛋白的表达。最近有人提出枸橼酸盐在代谢性骨病发病机制中的作用，并建议测量尿枸橼酸盐作为骨量丢失和骨折风险的预测指标。特发性钙结石病，无论有无低枸橼酸尿症，都可以用碱性枸橼酸盐治疗，其他形式的肾结石和不同的病理状况也可以用其治疗。在临床实践中，通常会开柠檬酸钾或枸橼酸镁钾进行治疗，以增加尿枸橼酸盐并降低结石形成率。我们的数据以及文献数据证实，碱性枸橼酸盐会导致保护性尿分析物（如枸橼酸盐、钾和pH值）增加，草酸钙饱和度降低。此外，碱处理可降低结石复发率，提高结石碎片的清除率和溶解率。最后但同样重要的是，越来越多的论文指出碱性枸橼酸盐在保护结石形成者以及有骨质流失的健康受试者骨量方面的保护作用。然而，对肾结石患者尿枸橼酸盐的评估以及用碱性盐（即柠檬酸钾）治疗这些患者的情况仍然很少。
