Low Serum Bicarbonate is Associated with Exercise Intolerance in Chronic Kidney Disease

Abstract

IntroductionChronic Kidney Disease (CKD) patients have exercise intolerance and exaggerated increases in blood pressure during exercise. Previous work from our group has shown that exaggerated increases in muscle sympathetic nerve activity (MSNA) due to enhanced muscle mechanoreflex activation contributes to the heightened exercise pressor response in CKD. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is increased muscle acidosis. CKD patients starting at Stage III have decreased bicarbonate bioavailability for buffering muscle pH changes, with or without overt metabolic acidosis, while pH is known to contribute to muscle afferent activation. Therefore, we hypothesized that patients with CKD stages III and IV with low serum [bicarbonate] would fatigue earlier, exhibit greater reductions in muscle interstitial pH, and greater MSNA and BP reactivity during exercise compared to those with normal serum [bicarbonate].Methods8 CKD participants (6M/2F) with normal serum [bicarbonate] (≥24mmol/L, normal‐bicarb), and 7 CKD participants (6M/1F) with low serum [bicarbonate] (≤22mmol/L, low‐bicarb) performed rhythmic handgrip at 40% of maximal voluntary contraction to volitional fatigue while heart rate (HR) via ECG, MSNA via microneurography, and arterial blood pressure via finger photoplethysmography were measured continuously. Contractions were performed for a duration of 3‐seconds at a rate of 1 contraction/4 seconds. A linear mixed model was used to compare the rate of increase in HR, systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) between groups.ResultsThe mean serum bicarbonate was 21.3±0.4mmol/L in the low‐bicarb group and 26.0±0.5mmol/L in the normal‐bicarb group (P<0.001). The low‐bicarb group reached volitional fatigue earlier than the normal‐bicarb group (low‐bicarb=187±26s vs normal‐bicarb=294±37s, P=0.04). There were no differences in the rate of increase in HR, or SAP between groups (P≥0.20). There was a trend towards a greater rate of increase in DAP during exercise in the low‐bicarb group compared to normal‐bicarb group (2.9 mmHg increase/30s vs 1.9mmHg increase/30s, P=0.18). Reliable MSNA measurements were obtained throughout the duration of maximum handgrip exercise in 1 low‐bicarb and 2 normal‐bicarb participants; MSNA reactivity data collection are ongoing.DiscussionIn support of our hypothesis, CKD participants with low serum bicarbonate reached volitional fatigue earlier and had a trend towards a greater rate of increase in DAP during exercise compared to CKD participants with normal bicarbonate levels. These findings suggest that low serum bicarbonate may be related to exercise intolerance and exaggerated exercise pressor response in patients with CKD stages III and IV.Support or Funding InformationThis work is supported by The National Institute of Health (R01HL135183 and T32DK007656).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.