All-cause and cause-specific mortality associated with diabetes in prevalent hemodialysis patients

Abdus Sattar, Christos Argyropoulos, Lisa Weissfeld, Nizar Younas, Linda Fried, John A Kellum, Mark Unruh, Abdus Sattar, Christos Argyropoulos, Lisa Weissfeld, Nizar Younas, Linda Fried, John A Kellum, Mark Unruh

Abstract

Background: Diabetes is the most common risk factor for end-stage renal disease (ESRD) and has been associated with increased risk of death. In order to better understand the influence of diabetes on outcomes in hemodialysis, we examine the risk of death of diabetic participants in the HEMODIALYSIS (HEMO) study.

Methods: In the HEMO study, 823 (44.6%) participants were classified as diabetic. Using the Schoenfeld residual test, we found that diabetes violated the proportional hazards assumption. Based on this result, we fit two non-proportional hazard models: Cox's time varying covariate model (Cox-TVC) that allows the hazard for diabetes to change linearly with time and Gray's time-varying coefficient model.

Results: Using the Cox-TVC, the hazard ratio (HR) for diabetes increased with each year of follow up (p = 0.02) for all cause mortality. Using Gray's model, the HR for diabetes ranged from 1.41 to 2.21 (p <0.01). The HR for diabetes using Gray's model exhibited a different pattern, being relatively stable at 1.5 for the first 3 years in the study and increasing afterwards.

Conclusion: Risk of death associated with diabetes in ESRD increases over time and suggests that an increasing risk of death among diabetes may be underappreciated when using conventional survival models.

Figures

Figure 1
Figure 1
All-cause and Cause-specific Adjusted Hazard Ratio for Diabetes Over Time in HEMO Study Patients§§.§§ (a) All-cause mortality HR estimate using the Cox’s proportional hazards (Cox-PH) is 2.11 (p = 0.003), HR for DM using Cox-TVC model is 1.57 (p = 0.11) for main effects and 1.13 (p = 0.02) for the interaction term, Gray’s model estimates are 1.41 to 2.21 (p <0.001). (b) Cardiac mortality HR estimate using the Cox-PH is 1.81 (p = 0.16), HR for DM using Cox-TVC model is 1.22 (p = 0.68) for main effects and 1.18 (p = 0.07) for the interaction term, Gray’s model estimates are 1.70 to 2.46 (p = 0.003). (c) Cardiovascular mortality HR estimate using the Cox-PH is 2.00 (p = 0.06), HR for DM using Cox-TVC model is 1.28 (p = 0.55) for main effects and 1.21 (p = 0.02) for the interaction term, Gray’s model estimates are 1.58 to 2.46 (p = 0.001). (d) Infectious mortality HR estimate using the Cox-PH is 2.01 (p = 0.22), HR for DM using Cox-TVC model is 1.48 (p = 0.53) for main effects and 1.12 (p = 0.27) for the interaction term, Gray’s model estimates are 1.17 to 2.21 (p = 0.21).

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