Association between Heart Rate Fragmentation and Kidney Function Decline in MESA: Evidence Consistent with Parasympathetic Degradation.

Abstract

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: (i) the likelihood of prevalent CKD and (ii) longitudinal changes in estimated glomerular filtration rate (eGFR) over approximately five years. The analytical cohort included 1,388 MESA participants (mean age: 66.8 ± 8.5 yrs; 44.5% male) with polysomnographic ECG recordings. Higher HRF, indicative of reduced parasympathetic function, was associated with (i) an increased likelihood of prevalent CKD (rate ratio: 1.15 [95% CI: 1.04; 1.27], per one-SD increase in HRF) and (ii) a steeper decline in eGFR (-0.86 [95%CI: -1.43; -0.28] mL/min/1.73 m2, per one-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 (1) early renal function decline in lower-risk populations and (2) 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.