Abate Nicola, Chandalia Manisha, Cabo-Chan Alberto V, Moe Orson W, Sakhaee Khashayar
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9169, USA.
Kidney Int. 2004 Feb;65(2):386-92. doi: 10.1111/j.1523-1755.2004.00386.x.
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.
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.
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).
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.
尿酸肾结石主要由低尿pH值引起，这会增加不溶性未解离尿酸的浓度，导致尿酸结石和尿酸/草酸钙混合结石的形成。最近有研究描述这些患者具有胰岛素抵抗的特征。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）尿pH值过低有关，以及胰岛素抵抗是否可以解释尿酸肾结石患者尿pH值过低的原因。
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常血糖钳夹试验、24小时尿液研究以及肥胖的人体测量。35名非结石形成者的一个亚组在钳夹试验的高胰岛素血症阶段之前和期间进行了2小时定时尿液收集。
对于非结石形成者群体，以葡萄糖处置率衡量的低胰岛素敏感性与低24小时尿pH值显著相关（r = 0.35；P = 0.01）。除了先前描述的酸性尿pH值和低尿酸尿症外，复发性尿酸肾结石患者被发现存在严重的胰岛素抵抗（葡萄糖处置率：尿酸结石形成者与正常人相比；4.1±1.3对6.9±2.1mg/min/kg瘦体重，P = 0.008）。急性高胰岛素血症与较高的尿pH值（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±1.6mEq/2小时，高胰岛素血症期间为4.0±2.6mEq/2小时，P = 0.002）和尿柠檬酸盐排泄（基线时为48±33mg/2小时，高胰岛素血症期间为113±68mg/2小时，P < 0.0001）相关。
我们得出结论，胰岛素抵抗的一种肾脏表现可能是低尿铵和低pH值。尽管尿酸排泄正常，但这种缺陷会导致尿酸沉淀风险增加。
