Association of Diabetes with Changes in Blood Pressure & Heart Rate Variability during Hemodialysis: Insights from The Frequent Hemodialysis Network Daily Trial

Abstract

Project 1 Abstract Title: Association of Diabetes with Changes in Blood Pressure during Hemodialysis:A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial. Introduction Diabetes mellitus is a common cause of kidney failure and is often complicated by autonomic neuropathy, which may have implications for blood pressure (BP) homeostasis during hemodialysis (HD). Methods In this post hoc analysis of the Frequent Hemodialysis Network (FHN) Daily Trial, we used random effects Poisson and linear regression models to estimate the association of diabetes (versus not) with intra-dialytic hypotension (IDH) and peri-dialytic BP parameters, respectively. We tested for differential associations according to the randomized treatment (6/week vs 3/week HD) and pre-HD systolic BP. Results Of the 244 patients with intra-dialytic BP data, 100 (41%) had diabetes at baseline. The mean age was 51 ± 14 years; 39% were female. In adjusted models, diabetes (vs. not) was associated with a 93% higher risk of developing IDH (IRR 1.93; 95% CI 1.26, 2.95). There was no evidence that the randomized treatment assignment modified the association between diabetes and IDH (P-interaction=0.32), but more potent associations were noted among those with higher pre-HD systolic BP (P-interaction .001). Diabetes (vs. not) was associated with a lower adjusted nadir intra-HD BP (-4.2; 95%CI -8.3, -0.2 mmHg), but not with the pre- or post-HD systolic BP. Conclusions Among participants of the FHN Daily trial, patients with diabetes had a higher risk of intra-dialytic hypotension and lower nadir intra-HD systolic BP than patients without diabetes, even when undergoing HD up to 6 times per week. Project 2 Abstract Title: Association of Diabetes with Heart Rate Variability during Hemodialysis: Insights from the Frequent Hemodialysis Network Daily Trial. Introduction Autonomic dysfunction is common among patients with diabetes receiving hemodialysis (HD). We wished to explore the association of diabetes with heart rate variability (HRV; a surrogate of autonomic dysfunction) and whether HRV mediates the association of diabetes with intra-dialytic hypotension (IDH). Methods In this secondary analysis of the Frequent Hemodialysis Network Daily Trial, we performed: 1) random effects linear regression to estimate the association of diabetes with log-transformed low-frequency power [LF, proxy of sympathetic activity], high-frequency power [HF, proxy of parasympathetic activity], ratio of LF/HF (proxy for sympathovagal balance), and standard deviation of the normal-to-normal R-R interval [SDNN] measured at baseline and 12-months); 2) linear regression to explore the association of diabetes with changes in HRV parameters over 12 months. Models were adjusted for age, sex, designated race, height, access type, HD vintage, history of heart failure, pre-HD systolic BP, heart rate, ultrafiltration rate, hemoglobin, serum albumin, beta-blocker use, calcium channel blocker use, diuretic use, left ventricular mass, and randomized treatment assignment. Results Of the 198 patients without baseline atrial fibrillation, 82 (41%) had self-reported diabetes. In adjusted random effects models, diabetes (vs. no diabetes) was associated with lower SDNN –18% (95%CI –27, –9) on a per session basis. The presence of diabetes was not associated with differences in LF 7% (95%CI –20, 43), HF 10% (95%CI –10, 33), or LF/HF –4% (95%CI –19, 14). Diabetes (vs. no diabetes) was not associated with a change from baseline to 12 months in any HRV parameter. SDNN did not attenuate the observed association of diabetes with IDH. Conclusions Among participants in the FHN Daily Trial, diabetes (vs. no diabetes) was associated with 18% lower SDNN. The association of diabetes with IDH did not appear to be mediated by SDNN. The reasons for higher rates of IDH in patients with diabetes remain elusive.