Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX.
Nephrology Section, Veterans Affairs San Diego Healthcare System, and Division of Nephrology-Hypertension, University of California-San Diego, La Jolla, CA.
Am J Kidney Dis. 2021 Aug;78(2):259-267. doi: 10.1053/j.ajkd.2020.11.030. Epub 2021 Feb 4.
RATIONALE & OBJECTIVE: Circulating nonesterified fatty acids (NEFAs) make up a small portion of circulating lipids but are a metabolically important energy source. Excessive circulating NEFAs may contribute to lipotoxicity in many tissues, including the kidneys. We investigated the relationship between total circulating NEFA concentration and kidney outcomes in older, community-dwelling adults.
Prospective cohort study.
SETTING & PARTICIPANTS: 4,698 participants≥65 years of age in the Cardiovascular Health Study who underwent total fasting serum NEFA concentration measurements in 1992-1993.
Fasting serum NEFA concentration at one time point.
Three primary outcomes: estimated glomerular filtration rate (eGFR) decline of≥30%, the composite of eGFR decline≥30% or kidney failure with replacement therapy, and change in eGFR. These outcomes were assessed over 4- and 13-year periods.
Logistic regression for the dichotomous outcomes and mixed effects models for the continuous outcome, with sequential adjustment for baseline covariates. Inverse probability of attrition weighting was implemented to account for informative attrition during the follow-up periods.
Serum NEFA concentrations were not independently associated with kidney outcomes. In unadjusted and partially adjusted analyses, the highest quartile of serum NEFA concentration (compared with lowest) was associated with a higher risk of≥30% eGFR decline at 4 years and faster rate of decline of eGFR. No associations were evident after adjustment for comorbidities, lipid levels, insulin sensitivity, medications, and vital signs: the odds ratio for the eGFR decline outcome was 1.33 (95% CI, 0.83-2.13), and the difference in eGFR slope in the highest versus lowest quartile of serum NEFA concentration was-0.15 (95% CI, -0.36 to 0.06) mL/min/1.73m per year.
Single NEFA measurements, no measurements of post-glucose load NEFA concentrations or individual NEFA species, no measurement of baseline urine albumin.
A single fasting serum NEFA concentration was not independently associated with long-term adverse kidney outcomes in a cohort of older community-living adults.
循环非酯化脂肪酸（NEFA）在循环脂质中所占比例较小，但却是一种重要的代谢能量来源。过多的循环 NEFA 可能导致包括肾脏在内的许多组织发生脂毒性。本研究旨在探讨老年社区居民中总循环 NEFA 浓度与肾脏结局之间的关系。
前瞻性队列研究。
入选心血管健康研究（1992-1993 年进行了空腹血清 NEFA 浓度检测）中年龄≥65 岁的 4698 名受试者。
单次空腹血清 NEFA 浓度。
肾小球滤过率（eGFR）下降≥30%、eGFR 下降≥30%或需肾脏替代治疗的复合结局以及 eGFR 变化。这些结局的评估时间分别为 4 年和 13 年。
二分类结局采用逻辑回归分析，连续结局采用混合效应模型分析，采用基线协变量的逐步调整。在随访期间采用逆概率删失加权来处理信息性删失。
血清 NEFA 浓度与肾脏结局无独立相关性。在未经调整和部分调整分析中，与最低四分位数相比，血清 NEFA 浓度最高四分位数与 4 年内 eGFR 下降≥30%的风险增加以及 eGFR 下降速度加快相关。在调整了合并症、血脂水平、胰岛素敏感性、药物和生命体征后，未观察到相关性：eGFR 下降结局的比值比为 1.33（95%CI，0.83-2.13），血清 NEFA 浓度最高与最低四分位数的 eGFR 斜率差值为-0.15（95%CI，-0.36 至 0.06）mL/min/1.73m/年。
单次 NEFA 测量、无葡萄糖负荷后 NEFA 浓度或个体 NEFA 种类测量、无基线尿白蛋白测量。
在老年社区居民队列中，单次空腹血清 NEFA 浓度与长期不良肾脏结局无独立相关性。
