Supplementary Material for: Risk Factors for Common Kidney Stones Are Correlated with Kidney Function Independent of Stone Composition

Background: Kidney stone type varies with age, sex, season, and medical conditions. Lower estimate glomerular filtration rate (eGFR) leads to changes in urine chemistry, and risk factors for kidney stones are thought to vary by stone type. We explore the association between eGFR, urine risk factors, and common stone compositions.

Methods: This was a retrospective cohort study of 811 kidney stone patients seen at Yale Medicine between 1994-2021 with serum chemistries and 24-hour urine chemistries matched within one year of baseline stone analysis. Patients’ eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Demographics and medical history were compared by Chi-squared tests. 24-hour urine chemistries and stone analyses were analyzed by one-way ANOVA. Linear regressions were performed to control for demographics, comorbidities, and stone composition.

Results: With lower eGFR, the proportion of calcium stones declined while uric acid stones increased. On univariable analysis, lower eGFR was associated with lower urine pH, calcium, citrate, uric acid, magnesium, phosphorus, and ammonium. On multivariable analysis, controlling for age, sex, ethnicity, BMI, comorbidities, and stone type, these factors remained significant. Stone formers with lower eGFR had elevated supersaturation for uric acid, but reduced supersaturations for calcium-containing stones. Though urine oxalate was significant on univariable analysis, it was not on multivariable analysis.

Discussion/Conclusion: Changes in urine parameters are strongly correlated with eGFR regardless of stone type. Renal function may play a key role in modulating kidney stone risk factors. Strategies to mitigate stone risk may need to vary with kidney function, especially when patient urine or stone composition data is unavailable.

研究背景：肾结石类型会随年龄、性别、季节以及基础疾病状态发生变化。较低的估算肾小球滤过率（estimated glomerular filtration rate，eGFR）会引发尿液化学成分改变，且现有研究认为肾结石的危险因素会因结石类型不同而存在差异。本研究旨在探讨eGFR、尿液危险因素与常见结石成分之间的关联。

研究方法：本研究为回顾性队列研究，纳入了1994年至2021年间在耶鲁医学（Yale Medicine）就诊的811名肾结石患者，所有患者均有血清化学检测结果，且在基线结石分析一年内匹配了24小时尿液化学检测数据。采用慢性肾脏病流行病学合作研究（Chronic Kidney Disease Epidemiology Collaboration，CKD-EPI）2021公式计算患者的eGFR。通过卡方检验比较患者的人口学特征与病史资料，采用单因素方差分析（one-way ANOVA）对24小时尿液化学指标及结石分析结果进行比较，并通过线性回归控制人口学特征、合并症与结石成分等混杂因素。

研究结果：随着eGFR降低，含钙结石的占比逐渐下降，而尿酸结石的占比则有所上升。单因素分析结果显示，eGFR较低与尿液pH值、钙、枸橼酸盐、尿酸、镁、磷及铵离子水平降低存在关联。在控制年龄、性别、种族、体质量指数（BMI）、合并症及结石类型等混杂因素的多因素分析中，上述关联仍具有统计学意义。eGFR较低的肾结石患者，其尿液中尿酸的过饱和度升高，而含钙结石的过饱和度则降低。尽管尿液草酸盐水平在单因素分析中具有统计学显著性，但在多因素分析中该关联不再显著。

讨论与结论：无论结石类型如何，尿液参数的变化均与eGFR密切相关。肾功能可能在调节肾结石危险因素方面发挥关键作用。因此，降低肾结石风险的干预策略可能需要根据患者肾功能水平进行调整，尤其是在无法获取患者尿液检测或结石成分数据的情况下。