The Association between Body Water Balance and Sympathetic Nervous Activity in Patients with Chronic Kidney Disease

Intro: Chronic kidney disease (CKD) is associated with both hypervolemia and sympathetic nervous system (SNS) overactivity that contribute to increased cardiovascular disease risk. While increased volume status classically results in suppression of SNS activity, SNS overactivity itself can contribute to volume retention by increasing sodium reabsorption from the kidneys. Given that both SNS and volume increase with worsening kidney function, this study aims to investigate the association between volume status and SNS activity and explore potential factors that may influence their relationship in patients with CKD. Method: 104 patients with CKD stage III-IV (age: 62 ± 12 yr, 67% men, 90% with hypertension) were tested for body fluid volume status by extracellular water/total body water (ECW/TBW) using multifrequency bioimpedance and SNS activity by muscle sympathetic nerve activity (MSNA) via microneurography. ECW/TBW tertiles were used for group comparison analysis, and linear associations were tested by Pearson correlation and multivariable regression tests. Results: MSNA was different among ECW/TBW tertile groups (p=0.009), with higher MSNA in T2 and T3 compared to MSNA in T1 (41 ± 14 and 35 ± 12 versus 26 ± 9 bursts/min, p=0.002 and 0.081 respectively) that remained significant after adjustment for eGFR, sex, age, and antihypertensive medication usage. ECW/TBW was associated with eGFR (r=-0.320, p<0.001) and age (r=0.319, p<0.001) and MSNA was associated with eGFR (r=-0.376, p=0.018). The combinations of MSNA and its interaction with eGFR centered on the mean (β = -0.001, p = 0.014) and its interaction with age centered on 65 yr (β = 0.001, p = 0.012) significantly predicted ECW/TBW (p = 0.009, R 2 adj = 0.214). Conclusion: Increased extracellular body fluid volume is associated with elevated SNS in patients with CKD. However, the relationship between SNS activity and volume status is modulated by declining kidney function and aging, with SNS not serving as an independent determinant of volume retention. These findings suggest that neural mechanisms may play a lesser role in CKD-associated volume retention. NIH R01HL135183; NIH R61AT10457; VA Merit I01CX001065; K01DK137620-01A1 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.