Zomorodian Alireza, Li Xilong, Poindexter John, Maalouf Naim M, Sakhaee Khashayar, Moe Orson W
Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Population and Data Science, University of Texas Southwestern Medical Center, Dallas, Texas.
Clin J Am Soc Nephrol. 2025 Jan 1;20(1):116-123. doi: 10.2215/CJN.0000000000000561. Epub 2024 Nov 1.
Under a controlled diet, uric acid stone formers (UASFs) and diabetic patients have higher endogenous net acid production. Under a controlled diet, UASFs have lower ammonium-to-net acid excretion ratio. Body fat inversely correlates with urine buffer capacity in normal individuals, but this relationship is lost in diabetic patients and UASFs.
Uric acid (UA) nephrolithiasis affects approximately 10% of kidney stones, with a greater preponderance among patients with obesity and diabetes mellitus (DM). UA lithogenicity is driven by abnormally acidic urine pH. Distinguishing the contribution of intrinsic (., body adiposity) versus external (., dietary) factors to UA stone propensity is challenging because of uncontrolled diets in outpatients in previously published studies.
This compilation of metabolic studies with body composition examined by dual-energy x-ray absorptiometry scan and blood and urine biochemistry collected under a controlled metabolic diet was conducted across three distinct populations: 74 UA stone formers (UASF group), 13 patients with type 2 DM without kidney stones (DM group), and 51 healthy volunteers (HV group).
Compared with HVs, both UASFs and patients with DM exhibited higher levels of net acid excretion (NAE) and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH/NAE), all under controlled diets. UASFs exhibited significantly lower NH/NAE compared with patients with DM. UASFs also showed higher total body and truncal fat compared with HVs. Among the HVs, lower NH/NAE ratio correlated with higher truncal and total fat. However, this association was abolished in the UASF and DM groups who exhibit a fixed low NH/NAE ratio across a range of body and truncal fat.
The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH excretion as major contributors to the risk of UA stone formation. There is an inverse physiologic association between body fat content and NH/NAE in HVs, whereas NH/NAE is persistently low in UASFs and patients with DM, regardless of body fat, representing pathophysiology.
在控制饮食的情况下，尿酸结石形成者（UASF）和糖尿病患者的内源性净酸生成较高。在控制饮食的情况下，UASF的铵排泄与净酸排泄比值较低。在正常个体中，体脂与尿液缓冲能力呈负相关，但在糖尿病患者和UASF中这种关系消失。
尿酸（UA）肾结石影响约10%的肾结石患者，在肥胖和糖尿病（DM）患者中更为常见。UA致石性由异常酸性的尿液pH值驱动。由于先前发表的研究中门诊患者饮食不受控制，区分内在因素（如身体肥胖）与外在因素（如饮食）对UA结石倾向的影响具有挑战性。
这项代谢研究汇编通过双能X线吸收法扫描检查身体成分，并在控制代谢饮食下收集血液和尿液生化指标，研究对象包括三个不同群体：74名尿酸结石形成者（UASF组）、13名无肾结石的2型糖尿病患者（DM组）和51名健康志愿者（HV组）。
与HV相比，在控制饮食的情况下，UASF和DM患者均表现出较高水平的净酸排泄（NAE）、显著较低的尿液pH值以及以铵（NH/NAE）形式排泄的NAE比例较低。与DM患者相比，UASF的NH/NAE显著更低。与HV相比，UASF的全身和躯干脂肪也更高。在HV中，较低的NH/NAE比值与较高的躯干和全身脂肪相关。然而，在UASF和DM组中，这种关联被消除，这两组在一系列身体和躯干脂肪水平下均表现出固定的低NH/NAE比值。
研究结果表明，与饮食无关的酸生成增加和肾脏NH排泄受损的双重缺陷是UA结石形成风险的主要因素。在HV中，体脂含量与NH/NAE之间存在反向生理关联，而在UASF和DM患者中，无论体脂如何，NH/NAE持续较低，代表了病理生理学特征。
