Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, California.
Division of Nephrology, Department of Medicine, University of California, San Francisco, California.
J Ren Nutr. 2023 May;33(3):428-434. doi: 10.1053/j.jrn.2023.01.007. Epub 2023 Feb 2.
Inflammation may be present with chronic kidney disease CKD and diet composition high in protein intake and fats may affect inflammation thereby impacting kidney health. We investigated whether acid load estimated from urine measures is associated with kidney function decline and whether the effect of acid load on an inflammatory marker, serum albumin, is a pathway to this association.
We studied 188 postmenopausal women in a randomized clinical trial of potassium bicarbonate treatment for up to 36 months. Twenty-four-hour urine and arterialized blood collections were done at baseline and at subsequent follow-up visits at 3 months interval. Acid load was estimated from potential renal acid load calculated using urinary measures of chloride, phosphate, sodium, potassium, calcium, and magnesium (UPRAL). Mixed effects model with random-intercept and slope was used to estimate subjects' annual decline rate in creatinine clearance (CrCl), and the association between (i) UPRAL and serum albumin and (ii) serum albumin and CrCl, adjusting for age, body mass index, systolic BP, and glucose. A Cox proportional regression model was used to study the relative hazard (RH) for rapid progression of kidney function decline (defined as loss of ≥5 mL/min CrCl/yr based on the last CrCl in the rolling window) with UPRAL, adjusting for the potential covariates and baseline CrCl.
A 25 mEq/day increase in UPRAL was inversely associated with serum albumin (Adjusted β[95% CI]: -0.02[-0.09;-0.001). During a mean follow-up of 28 months, 19 women (10%) had a rapid decline in kidney function. For each 25 mEq/day increase in UPRAL, the risk of a rapid decline in CrCl increased by 17% (95% CI: 1.06-1.28). On adjustment for potential confounders, the risk attenuated to 5% (1.02-1.14). Mediation analysis indicated that of the total effect of the association between UPRAL and CrCl, the proportion mediated by serum albumin increased to 0.346 (i.e. 34.6%).
Higher UPRAL was associated with lower serum albumin as well as greater kidney function decline in postmenopausal women. Our findings suggest inflammatory response may exert a modulatory effect on the association of UPRAL and kidney function and might be a potential pathway explaining the effects of systemic acid load on progression of kidney failure.
慢性肾脏病（CKD）患者可能存在炎症，而高蛋白和高脂肪的饮食成分可能会影响炎症，从而影响肾脏健康。我们研究了尿液测量估计的酸负荷是否与肾功能下降有关，以及酸负荷对血清白蛋白这一炎症标志物的影响是否是这种关联的途径。
我们对参加为期 36 个月的碳酸氢钾治疗的随机临床试验的 188 名绝经后妇女进行了研究。在基线和随后的每 3 个月随访时进行 24 小时尿液和动脉化血液采集。使用尿中氯、磷酸盐、钠、钾、钙和镁（UPRAL）的测量值计算潜在肾酸负荷来估计酸负荷。采用具有随机截距和斜率的混合效应模型来估计受试者肌酐清除率（CrCl）的年下降率，以及（i）UPRAL 与血清白蛋白和（ii）血清白蛋白与 CrCl 之间的关系，调整年龄、体重指数、收缩压和血糖。使用 Cox 比例风险回归模型研究 UPRAL 与肾功能下降（定义为基于滚动窗口中的最后一次 CrCl，每年损失≥5ml/min CrCl/yr）的相对危险（RH），调整潜在协变量和基线 CrCl。
UPRAL 增加 25mEq/天与血清白蛋白呈负相关（调整后β[95%CI]：-0.02[-0.09;-0.001]）。在平均 28 个月的随访期间，19 名女性（10%）肾功能迅速下降。对于 UPRAL 每增加 25mEq/天，CrCl 快速下降的风险增加 17%（95%CI：1.06-1.28）。在调整潜在混杂因素后，风险降低至 5%（1.02-1.14）。中介分析表明，在 UPRAL 与 CrCl 之间关联的总效应中，血清白蛋白介导的比例增加到 0.346（即 34.6%）。
绝经后妇女的 UPRAL 越高，血清白蛋白越低，肾功能下降越大。我们的研究结果表明，炎症反应可能对 UPRAL 与肾功能之间的关联产生调节作用，并且可能是解释全身酸负荷对肾衰竭进展影响的潜在途径。
