Aerobic Exercise Training Does Not Improve Vagal Reactivation in Patients with Chronic Kidney Disease

Parasympathetic reactivation is the underlying mechanism for the rapid fall in heart rate (HR) post-exercise. A delayed decrease in the HR during the first minute after graded exercise is a powerful predictor of overall mortality and is linked to unfavorable clinical outcomes. Chronic kidney disease (CKD) is characterized by an altered autonomic function with heightened sympathetic and weakened parasympathetic activity. Given that exercise training has been shown to improve autonomic function and parasympathetic reactivation after exercise, the purpose of the present study was to test two hypotheses: 1) patients with CKD experience delayed HR recovery (HRR) compared to controls at the cessation of exercise due to attenuated cardiac vagal reactivation; 2) 12 weeks of aerobic exercise training would improve cardiac vagal reactivation in patients with CKD. Twenty-seven patients with CKD stages III and IV [eGFR between 15-59 mL/min/1.73m 2 ] and eighteen age-matched controls were enrolled. All participants underwent cardiopulmonary exercise testing (CPET) in accordance with the modified Balke protocol. Participants were instrumented with a 12-lead ECG for HR assessment, and ventilation and pulmonary gas exchange were recorded breath-by-breath throughout the exercise tests using a metabolic analyzer. Post-exercise cardiac vagal reactivation was indexed via HRR [absolute HR decay (HRR60s)] and HR variability (HRV) metrics [root mean square of successive differences (RMSSD)] during 60 seconds of recovery following the test. To assess HRR kinetics over the entire recovery period, individual data were modeled with a monoexponential fit and the time constant (τ, time to reach ~63.2% of the total HRR, in seconds) was calculated. Comparisons between patients with CKD and controls were made based on the percentage of predicted HR max obtained during the CPET using the following equation: HR max= 208−0.7xage. Patients with CKD were then randomly assigned to exercise (n=17) or non-aerobic stretching (n=11) interventions consisting of three sessions per week for 12 weeks. Training sessions began at 20 minutes and increased by five minutes weekly to a maximum of 45 minutes. Intensity started at 50% of heart rate reserve and rose 5% each week to a target of 75%. CPET was repeated at the end of the 12 weeks. The percentage of predicted HR max obtained at CPET was similar between patients and controls (CKD: 87±9 vs. CON: 86±5 %HR max ; P =0.448). The HRR60s was blunted in patients with CKD compared to controls (∆HRR60s; CKD: -11±4 vs. CON: -17±5 bpm; P =0.001), and τ was significantly longer in patients with CKD (τ; CKD: 144±31 vs. CON: 116±21 s; P = 0.002). Additionally, RMSSD increased at the cessation of exercise in both groups, but to a lesser extent in CKD patients compared to controls (ΔRMSSD; CKD: 0.5±4 vs. CON: 1.3±3 ms; P = 0.032). There was no significant difference in the maximum HR obtained during the CPET before and after 12 weeks of exercise training (pre: 142±10 vs. post: 136±20 bpm, P =0.178) or stretching (pre: 148±20 vs. post: 142±20 bpm, P =0.107). Twelve weeks of exercise training did not improve HRR60s (ΔHRR60s; pre: -11±4 vs. post: -11±8 bpm, P =0.692) nor vagal activity as measured by HRV. These findings support the hypothesis that patients with CKD exhibit impaired vagal reactivation, which may contribute to the increased cardiovascular risk associated with CKD. However, contrary to our hypothesis, 12 weeks of cycling exercise training may not be sufficient to enhance cardiac vagal reactivation. Future studies should explore different exercise modalities and manipulate training variables such as intensity, volume, and frequency to assess their potential impact on cardiac vagal reactivation in patients with CKD. This project was funded by the National Institutes of Health (NIH R01HL135183; NIH R61AT10457; NIH R33AT010457-03). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.