Costa Madalena D, Redline Susan, Bansal Nisha, Heckbert Susan R, Goldberger Ary L
Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States.
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts, United States.
Am J Physiol Regul Integr Comp Physiol. 2025 Jul 1;329(1):R186-R194. doi: 10.1152/ajpregu.00091.2025. Epub 2025 May 30.
The contribution of sympathetic overactivity to the pathogenesis of chronic kidney disease (CKD) is well established; in contrast, the role of the parasympathetic system in renal homeostasis remains less well understood. Studies in animal models suggest that parasympathetic activity may influence kidney function by buffering sympathetic tone, activating the cholinergic anti-inflammatory pathway, and modulating cardiovascular (CV) function. We investigated whether a novel noninvasive marker of parasympathetic function, heart rate fragmentation (HRF), was associated with ) the likelihood of prevalent CKD and ) longitudinal changes in estimated glomerular filtration rate (eGFR) over ∼5 yr. The analytical cohort included 1,388 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) (mean age: 66.8 ± 8.5 yr; 44.5% male) with polysomnographic ECG recordings. Higher HRF, indicative of reduced parasympathetic function, was associated with ) an increased likelihood of prevalent CKD (rate ratio: 1.15 [95% confidence interval (CI): 1.04; 1.27], per 1-SD increase in HRF) and ) a steeper decline in eGFR (-0.86 [95% CI: -1.43; -0.28] mL/min/1.73 m, per 1-SD increase in HRF), independent of major comorbidities, including age, hypertension, diabetes, and baseline CKD status. Stratified analyses in lower- and higher-risk subgroups yielded consistent results. These findings support a role for parasympathetic activity in renal homeostasis and suggest that HRF may serve as a noninvasive biomarker of risk for ) early renal function decline in lower-risk populations and ) accelerated decline in the general and higher-risk populations. HRF may also be useful for evaluating interventions targeting renal neuroautonomics, such as vagal stimulation or renal sympathetic denervation. This study identifies reduced cardiac parasympathetic activity, measured by heart rate fragmentation (HRF), as a potential contributor to accelerated renal function decline in a community-based population. The findings suggest a mechanistic link between vagal dysfunction and kidney deterioration. From a translational perspective, the results support the utility of HRF-a noninvasive, repeatable measure-for renal disease risk stratification and monitoring of autonomic-targeted interventions.
交感神经过度活跃在慢性肾脏病（CKD）发病机制中的作用已得到充分证实；相比之下，副交感神经系统在肾脏内环境稳定中的作用仍不太清楚。动物模型研究表明，副交感神经活动可能通过缓冲交感神经张力、激活胆碱能抗炎途径和调节心血管（CV）功能来影响肾功能。我们调查了一种新型的副交感神经功能非侵入性标志物——心率变异性（HRF），是否与）CKD患病率以及）约5年内估算肾小球滤过率（eGFR）的纵向变化相关。分析队列包括多族裔动脉粥样硬化研究（MESA）中的1388名参与者（平均年龄：66.8±8.5岁；44.5%为男性），他们均有多导睡眠图心电图记录。较高的HRF表明副交感神经功能降低，与）CKD患病率增加相关（率比：1.15 [95%置信区间（CI）：1.04；1.27]，HRF每增加1个标准差）以及）eGFR下降更陡峭（-0.86 [95% CI：-1.43；-0.28] mL/min/1.73 m²，HRF每增加1个标准差），独立于主要合并症，包括年龄、高血压、糖尿病和基线CKD状态。在低风险和高风险亚组中的分层分析得出了一致的结果。这些发现支持了副交感神经活动在肾脏内环境稳定中的作用，并表明HRF可能作为一种非侵入性生物标志物，用于评估）低风险人群早期肾功能下降风险以及）一般人群和高风险人群肾功能加速下降风险。HRF也可能有助于评估针对肾脏自主神经功能的干预措施，如迷走神经刺激或肾交感神经去神经支配。本研究确定，通过心率变异性（HRF）测量的心脏副交感神经活动降低是社区人群肾功能加速下降的一个潜在因素。这些发现提示了迷走神经功能障碍与肾脏损害之间的机制联系。从转化医学角度来看，结果支持了HRF（一种非侵入性、可重复的测量方法）在肾脏疾病风险分层和自主神经靶向干预监测中的实用性。
