Abstract: SA-PO0433
Systemic Inflammation Mediates the Association of Kidney Function with Heart Rate Variability in CKD: The CRIC Study
Session Information
- CKM: Clinical - Epidemiology and Outcomes
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Soomro, Qandeel H., New York University, New York, New York, United States
- Moran, David H., New York University, New York, New York, United States
- Charytan, David M., New York University, New York, New York, United States
- Lee, Myeonggyun, New York University, New York, New York, United States
Background
Autonomic dysfunction in chronic kidney disease (CKD) contributes to arrhythmia susceptibility and cardiovascular mortality. Whether systemic inflammation mediates the association between kidney function and heart rate variability (HRV) remains incompletely characterized.
Methods
We conducted a cross-sectional analysis of 5,456 Chronic Renal Insufficiency Cohort (CRIC) participants with baseline eGFR (CKD-EPI 2021) and SDNN (standard deviation of N-N intervals derived from 10-second 12-lead ECGs, a marker of global autonomic activity). Multivariable linear regression adjusted for age, sex, and diabetes was used to assess eGFR–SDNN associations and effect modification by hs-CRP, IL-6, and TNF-α. Formal mediation analysis with 1,000 bootstrap iterations decomposed total effects into direct and indirect (through each inflammatory marker) pathways. eGFR was scaled per 10 mL/min/1.73m2 and centered; inflammatory markers were log2-transformed and centered; SDNN was log-transformed.
Results
Median log(SDNN) declined progressively across CKD stages (mild 2.8 → advanced 2.6; p<0.001). Higher eGFR was associated with greater log(SDNN): β=0.03 (hs-CRP model), β=0.05 (IL-6), β=0.05 (TNF-α); all p<0.001. Each two-fold increase in any inflammatory marker was independently associated with lower SDNN. hs-CRP significantly modified the eGFR–SDNN association (interaction p=0.008), attenuating the slope by 53% at +1 SD vs −1 SD. IL-6 (p=0.36) and TNF-α (p=0.55) did not modify the association. In mediation analyses: TNF-α explained 18.3% of the eGFR effect (ACME 0.011 [0.006, 0.016]; p=0.002), IL-6 13.0% (p<0.001), hs-CRP 3.4% (p<0.001).
Conclusion
Lower kidney function is independently associated with reduced HRV. Inflammation modified the kidney–autonomic axis through two distinct ways: hs-CRP modifies the eGFR–HRV slope, while TNF-α and IL-6 act predominantly as mediators, with TNF-α as the dominant mediator. Combined kidney function preservation and targeted anti-inflammatory therapy may represent a therapeutic strategy for autonomic dysfunction in CKD.
Acknowledgment
CRIC investigators
Funding
- NIDDK Support