The metabolic syndrome and uric acid nephrolithiasis: Novel features of renal manifestation of insulin resistance
The metabolic syndrome and uric acid nephrolithiasis: Novel features of renal manifestation of insulin resistance
复制标题
DOI：
10.1111/j.1523-1755.2004.00386.x
复制
发表时间：
2004-02-01
影响因子：
19.6
通讯作者：
Sakhaee, K
中科院分区：
文献类型：
--
作者：
Abate, N;Chandalia, M;Sakhaee, K
背景尿酸肾结石主要是由于尿液pH值低，这增加了不溶性未解离尿酸的浓度，导致尿酸和混合尿酸/草酸钙结石的形成。这些患者最近被描述为表现出胰岛素抵抗的特征。本研究旨在评估胰岛素抵抗是否与明显健康的志愿者（非结石形成者）的尿液pH值过低相关，以及胰岛素抵抗是否可以解释尿酸性肾结石患者的尿液pH值过低。55名体重指数范围较大的健康志愿者（非结石形成者）和13名复发性尿酸肾结石患者接受了高胰岛素正葡萄糖钳夹、24小时尿液研究和肥胖的人体测量。一个由35名非结石形成者组成的亚组在钳夹研究的高胰岛素血症期之前和期间进行2小时定时尿收集。对于非结石患者，低胰岛素敏感性（葡萄糖处理率）与24小时尿pH值低显著相关（r = 0.35; P = 0.01）。除了先前描述的酸性尿pH和低尿酸尿外，发现复发性尿酸肾结石患者存在严重的胰岛素抵抗（葡萄糖处置率：尿酸结石形成者vs.正常人; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg瘦体重，P = 0.008）。急性高胰岛素血症与尿pH值升高有关（基线时为6.1 ± 0.7，高胰岛素血症期间为6.8 ± 0.7; P < 0.0001），尿氨排泄（基线时为2.7 +/- 1.6 mEq/2 hr，P = 0.002）和尿柠檬酸盐排泄（基线时48 +/- 33 mg/2 hr和113 +/- 68 mg/2 hr P < 0.0001）。我们的结论是，胰岛素抵抗的肾脏表现之一可能是低尿铵和pH值。这种缺陷可能会导致尿酸沉淀的风险增加，尽管正常尿酸尿。
Background. Uric acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated uric acid, causing formation of both uric acid and mixed uric acid/calcium oxalate stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with uric acid nephrolithiasis.Methods. Fifty-five healthy volunteers (non stone-formers) with a large range of body mass index and 13 patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies.Results. For the non-stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH (r = 0.35; P = 0.01). In addition to the previously described acidic urine pH and hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs. normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P = 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P = 0.002) and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2 hr P < 0.0001).Conclusion. We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of uric acid precipitation despite normouricosuria.