Schwille P O, Herrmann U, Schmiedl A, Kissler H, Wipplinger J, Manoharan M
University Hospital, Department of Surgery, Erlangen, Germany.
Urol Res. 1997;25(6):417-26. doi: 10.1007/BF01268860.
Previous work in younger males with recurrent idiopathic calcium urolithiasis (RCU) demonstrated inappropriately high postprandial phosphaturia, hyperinsulinemia and insulin resistance, but normal glycemia. To investigate further whether these abnormalities occur also in RCU patients with a mean age corresponding to the life period with peak formation of calcium-containing stones, two trials were carried out in 155 males of comparable age and body mass index. All participants underwent a standardized laboratory examination, including collection of urine and blood before and following a test meal rich in carbohydrate and calcium but low in phosphorus. In trial 1, comprising control subjects (n = 12, mean age 42 years) and RCU patients (n = 24, mean age 41 years), phosphate (Pi) excretion and fractional Pi excretion in postprandial urine of controls did not change compared with the values in fasting urine, but were significantly increased in RCU, despite the fact that there was almost equal suppression of serum parathyroid hormone (PTH) and increase in serum calcitonin. Postprandially, RCU patients were hyperinsulinemic but still normoglycemic versus controls. In trial 2, carried out in unclassified (in terms of calciuria) RCU patients (n = 119, mean age 40 years) only, the post-load Pi-uria was similar in magnitude to Pi-uria of RCU patients in trial 1; increased postprandial Pi-uria was a phenomenon also of normocalciuria but was slightly more pronounced in hypercalciuria, while changes in calcium phosphate (brushite) and calcium oxalate supersaturation of urine were unrelated to calciuria. In RCU patients, but not controls, there was a tendency toward higher urinary glucose in post-load as compared with fasting urine. When urinary Pi and fractional Pi excretion in trial 2 were considered as dependent variables in multivariate regression analysis, they appeared unrelated to age, but positively associated with postprandial glycemia as the best predictor, followed by insulinemia, insulin resistance, to a lesser degree fasting serum PTH and the metabolic activity of stone disease, negatively associated with blood total lipids and very low density lipoprotein (VLDL) cholesterol. It was concluded that RCU males (1) show low Pi-uria during fasting but impaired renal Pi conservation in response to a mixed meal, a situation carrying the risk of Pi deficiency over the long term; (2) represent a population developing hyperPi-uria despite suppressed PTH; (3) exhibit insulin resistance but are still able to maintain normoglycemia at the expense of hyperinsulinemia. It is suggested that calcium-containing renal stones are related to impaired Pi and glucose translocation across cell membranes, and that the role of lipids in this setting deserves further investigation.
先前针对复发性特发性钙尿路结石（RCU）的年轻男性开展的研究表明，这些患者餐后磷尿症过高、存在高胰岛素血症和胰岛素抵抗，但血糖正常。为了进一步研究在平均年龄与含钙结石形成高峰期相对应的RCU患者中是否也会出现这些异常情况，我们对155名年龄和体重指数相当的男性进行了两项试验。所有参与者都接受了标准化实验室检查，包括在摄入富含碳水化合物和钙但磷含量低的试验餐前后收集尿液和血液。在试验1中，包括对照组（n = 12，平均年龄42岁）和RCU患者（n = 24，平均年龄41岁），与空腹尿液中的值相比，对照组餐后尿液中的磷酸盐（Pi）排泄量和Pi排泄分数没有变化，但在RCU患者中显著增加，尽管血清甲状旁腺激素（PTH）几乎受到同等程度的抑制且血清降钙素增加。餐后，与对照组相比，RCU患者存在高胰岛素血症但血糖仍正常。在试验2中，仅对未分类（根据尿钙情况）的RCU患者（n = 119，平均年龄40岁）进行了研究，负荷后Pi尿的幅度与试验1中RCU患者的Pi尿相似；餐后Pi尿增加也是正常尿钙患者的一种现象，但在高尿钙患者中更为明显，而尿液中磷酸钙（透钙磷石）和草酸钙过饱和度的变化与尿钙情况无关。与空腹尿液相比，在RCU患者而非对照组中，负荷后尿葡萄糖有升高趋势。当将试验2中的尿Pi和Pi排泄分数作为多元回归分析中的因变量时，它们似乎与年龄无关，但与餐后血糖呈正相关，餐后血糖是最佳预测指标，其次是胰岛素血症、胰岛素抵抗，在较小程度上与空腹血清PTH和结石病的代谢活性相关，与血液总脂质和极低密度脂蛋白（VLDL）胆固醇呈负相关。研究得出结论，RCU男性（1）空腹时Pi尿较低，但对混合餐的反应是肾脏Pi保留受损，这种情况长期存在Pi缺乏的风险；（2）是一群尽管PTH受到抑制但仍会出现高Pi尿的人群；（3）表现出胰岛素抵抗，但仍能够以高胰岛素血症为代价维持血糖正常。有人提出，含钙肾结石与Pi和葡萄糖跨细胞膜转运受损有关，脂质在这种情况下的作用值得进一步研究。
