Abstract: FR-PO269
Insulin Sensitivity and Systemic Inflammation Are Potential Mediators of the Association Between Serum Uromodulin and Arterial Stiffness Among Nondiabetic Patients with CKD
Session Information
- CKD: Epidemiology and Risk Factors
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Akwo, Elvis A., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Alsouqi, Aseel, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Deger, Serpil muge, Vanderbilt University Faculty of Medicine Department of Nephrology, Nashville, Tennessee, United States
- Siew, Edward D., Vanderbilt University School of Medicine, Nashville, Tennessee, United States
- Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Hung, Adriana, VA & Vanderbilt University, Nashville, Tennessee, United States
Background
Patients with chronic kidney disease (CKD) have an elevated risk of premature death due to cardiovascular disease (CVD) beyond what is predicted by traditional CVD risk factors. Serum uromodulin (sUmod) is a potential non-traditional CVD risk factor. The relationship between sUmod and subclinical CVD is not well described. We investigated the relationship between sUmod and aortic pulse wave velocity (PWV).
Methods
Participants included 73 CKD and 116 normal GFR patients who underwent a comprehensive clinical assessment including PWV measurement (via applanation tonometry) and clamp-derived insulin sensitivity index (ISI). Biomarkers included sUmod, creatinine-based eGFR and high sensitivity C-reactive peptide (hsCRP). Sequential linear models with robust standard errors were used to examine the relationship between sUmod and PWV and perform mediation analyses.
Results
Mean age was 55 (15) years; 45% were female, 34% African American. sUmod had a significant positive correlation with eGFR (r = 0.65; p < 0.01) and log ISI (r = 0.27, p < 0.01) and inverse correlations with log hsCRP (r = -0.27; p < 0.01) and PWV (r = -0.46, p < 0.01). A one interquartile range lower sUmod was associated with a 1.45 m/s increase (95% CI: 1.02, 1.89; p < 0.01) in PWV in the unadjusted model. Adjustment for demographics and mean arterial pressure attenuated the effect estimate [0.42 m/s; 95% CI: 0.05, 0.79; p = 0.03]. Additional adjustment for log hsCRP and log ISI further diminished the sUmod effect [0.18 m/s; 95% CI: -0.18, 0.53; p = 0.3].
Conclusion
Declining sUmod levels is associated with increased PWV, a subclinical marker of CVD that reflects arterial stiffness. This relationship appears to be mediated, in part, by systemic inflammation and insulin resistance.
Funding
- Veterans Affairs Support