Background: A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence - not only for type 2 diabetes patients, but also for healthy individuals - that higher body fatness or waist circumference (WC) negatively impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules may mediate this relation between adiposity and renal acid excretion function. Methods: Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25y) of the DONALD study, who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's steps (B&Ks) to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24h-pH relationship after strictly controlling for lab-measured NAE. Results: In B&Ks mediation analysis, leptin, soluble intercellular adhesion molecule-1 (sICAM-1), and adiponectin significantly associated with the outcome 24h-pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24h-pH via leptin (P=0.01) and adiponectin (P=0.03) to be significant with a trend for sICAM-1 (P=0.09). The calculated proportions mediated by leptin, adiponectin and sICAM-1 were 64%, 23%, and 12%, respectively. Conclusion: Both mediation analyses identified an inflammatory (leptin) and an anti-inflammatory (adiponectin) cytokine along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

中文翻译：

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脂肪-肾轴的炎症介质：瘦素，脂联素和可溶性ICAM-1。

背景：在给定的人体酸负荷下，较低的24小时尿液pH（24h-pH），即较高的肾脏肾脏游离质子排泄量，表明肾脏的净酸排泄能力（NAE）降低。越来越多的证据-不仅对于2型糖尿病患者，而且对于健康个体-更高的体脂或腰围（WC）对肾功能排泄酸（NAE）都有负面影响。我们假设肥胖相关的炎症分子可能介导肥胖与肾酸排泄功能之间的这种关系。方法：在来自DONALD研究的162名成年参与者（18-25岁）的空腹血液样本中测量了十二种炎症生物标记物，他们经过人体测量并收集了24小时尿液样本。男爵和肯尼的脚步（B＆在严格控制实验室测量的NAE之后，进行了Ks）测试介导和因果介导分析，以检查WC-24h-pH关系中炎症生物标志物的潜在介导作用。结果：在B＆K介导的分析中，瘦素，可溶性细胞间粘附分子1（sICAM-1）和脂联素与结果24h-pH显着相关，并减弱了WC-pH关系。与此一致的是，因果关系分析估计，WC通过瘦素（P = 0.01）和脂联素（P = 0.03）对24h-pH值具有“自然间接作用”，并且具有sICAM-1的趋势（P = 0.09）。瘦素，脂联素和sICAM-1介导的计算比例分别为64％，23％和12％。结论：