Kidney Week

Abstract: TH-PO1135

Insulin Sensitivity, Systemic Inflammation and GFR as Key Determinants of Arterial Stiffness

Session Information

• CKD: Clinical, Outcomes, Trials - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Akwo, Elvis A., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Elvis A. Akwo,

• Alsouqi, Aseel, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Aseel Alsouqi,

• Whitfield, Victoria, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Victoria Whitfield,

• Wanko, Lori, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Lori Wanko,

• Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Talat Alp Ikizler,

• Hung, Adriana, Veterans Affairs CSR&D, Nashville, Tennessee, United States

Adriana Hung,

Background

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease (CVD). The underlying mechanisms of the burden of CVD in CKD remains poorly understood. We investigated the relationship of GFR, aortic arterial stiffness and the mediating effects of systemic inflammation and insulin sensitivity.

Methods

We studied 136 patients: 50 CKD and 86 normal GFR. Aortic pulse wave velocity (aPWV) was measured via transcutaneous tonometry. Insulin sensitivity index (ISI) was measured by hyperinsulinemic euglycemic clamp; high sensitivity C-reactive protein (hsCRP) and eGFR were measured at baseline. Sequential multivariable linear regression with robust standard errors was used to study determinants of aPWV and perform mediation analyses.

Results

Median age was 54 years; 51% were female and 38% African-American. Patients with CKD had significantly higher aPWV [10.7±2.2 vs. 7.7±1.4, p < 0.0001] compared to controls. Log aPWV was inversely correlated with eGFR (r = - 0.65, p < 0.0001) and log ISI (r = -0.38, p < 0.0001); and was positively correlated with age (r = 0.73, p < 0.0001), BMI (r = 0.17, p = 0.02) and log hsCRP (r = 0.23, p <0.0001). In the model adjusted for: age, sex, race, BMI and smoking, a 10 ml/min decrease in eGFR was associated with a 2.1% increase (95% CI: 0.8, 3.3, p = 0.001) in aPWV. Further adjustment for log ISI and log hsCRP attenuated the eGFR effect (percent increase in PWV = 1.4%, 95% CI: - 0.2, 3.0, p = 0.1). GFR had a significant (p = 0.01) inverse nonlinear association with CPP that became insignificant when adjusting for hsCRP and/or ISI [Figure 1].

Conclusion

Declining GFR is associated with increased aPWV and CPP. These adverse vascular outcomes in CKD are partly mediated by systemic inflammation and insulin resistance. Targetting both IS an/or inflammation could reduce CVD risk in CKD patients.

Funding

• Veterans Affairs Support