Changes in pulse pressure during hemodialysis treatment and survival in maintenance dialysis patients

Abstract

Background and objectives: Pulse pressure has been shown as a risk factor for mortality in patients on maintenance hemodialysis (MHD). However, the effect of change in pulse pressure during hemodialysis on survival in a large cohort of patients on MHD has not been sufficiently investigated.

Design, setting, participants, & measurements: This study examined the association between time-varying Δ pulse pressure (postdialysis minus predialysis pulse pressure) and mortality in a cohort of 98,577 patients on MHD (July 2001-June 2006) using Cox proportional hazard models with restricted cubic splines.

Results: The average patient age was 62 years old; among the patients, 33% were black and 59% had diabetes. During 134,814 patient-years of at-risk time, 16,054 (16%) patients died, with 6827 (43%) of the deaths caused by cardiovascular causes. In the models including adjustment for either predialysis systolic BP or mean arterial BP, there was a U-shaped association between change in pulse pressure during hemodialysis and all-cause mortality. In the systolic BP plus case mix plus malnutrition-inflammation complex syndrome-adjusted model, large declines in pulse pressure (>-25 mmHg) and increases in pulse pressure >5 mmHg were associated with higher all-cause mortality (reference: ≥-5 to <5 mmHg): hazard ratios (95% confidence intervals [95% CIs]) for change pulse pressures of <-25, ≥-25 to <-15, ≥-15 to <-5, 5 to <15, 15 to <25, and ≥25 mmHg were 1.21 (95% CI, 1.14 to 1.29), 1.03 (95% CI, 0.97 to 1.10), 1.01 (95% CI, 0.96 to 1.06), 1.06 (95% CI, 1.01 to 1.11), 1.17 (95% CI, 1.11 to 1.24), and 1.15 (95% CI, 1.08 to 1.23), respectively. The U-shaped association was observed with cardiovascular death.

Conclusions: Modest reductions in pulse pressure after hemodialysis are associated with the greatest survival, whereas large declines or rises in pulse pressure are related to higher mortality. Trials determining how to modify pulse pressure response to improve survival in the hemodialysis population are indicated.

Keywords: hemodialysis; hemodynamics and vascular regulation; survival.

Figure 1.

SBP-adjusted hazard ratio for the association between change in pulse pressure during hemodialysis and all-cause mortality. Minimally SBP-adjusted model (A) and SBP plus case-mix plus MICS-adjusted model (B). Dashed lines represent 95% confidence interval. Change in PP was defined as postdialysis PP minus predialysis PP. Minimally SBP-adjusted model included adjustment for entry calendar quarter and predialysis SBP. SBP plus case mix plus MICS-adjusted model included covariates in the minimally SBP-adjusted model plus age, sex, race/ethnicity, presence of diabetes mellitus, nine preexisting comorbidities, history of tobacco smoking, dialysis duration categories, primary insurance, types of vascular access, dialysis dose as indicated by single pool Kt/V, ultrafiltration percentage, body mass index, serum levels of albumin, creatinine, total iron-binding capacity, ferritin, calcium, phosphorus, bicarbonate, hemoglobin, blood white blood cells, and lymphocyte percentage. MICS, malnutrition-inflammation complex syndrome; PP, pulse pressure; SBP, systolic BP.

Figure 2.

MAP-adjusted hazard ratio for the association between change in pulse pressure during hemodialysis and all-cause mortality. Minimally MAP-adjusted model (A) and MAP plus case-mix plus MICS-adjusted model (B). Dashed lines represent 95% confidence interval. Change in PP was defined as postdialysis PP minus predialysis PP. Minimally MAP-adjusted model included adjustment for entry calendar quarter and predialysis MAP. MAP plus case mix plus MICS-adjusted model included covariates in the minimally MAP-adjusted model plus age, sex, race/ethnicity, presence of diabetes mellitus, nine preexisting comorbidities, history of tobacco smoking, dialysis duration categories, primary insurance, types of vascular access, dialysis dose as indicated by single pool Kt/V, ultrafiltration percentage, body mass index, serum levels of albumin, creatinine, total iron-binding capacity, ferritin, calcium, phosphorus, bicarbonate, hemoglobin, blood white blood cells, and lymphocyte percentage. MAP, mean arterial BP; MICS, malnutrition-inflammation complex syndrome; PP, pulse pressure.

Figure 3.

Effect modification by predialysis SBP on the association between change in pulse pressure and all-cause mortality for case mix plus MICS–adjusted models. Change in PP was defined as postdialysis PP minus predialysis PP. Case mix plus MICS-adjusted model included adjustment for entry calendar quarter, age, sex, race/ethnicity, presence of diabetes mellitus, nine preexisting comorbidities, history of tobacco smoking, dialysis duration categories, primary insurance, types of vascular access, dialysis dose as indicated by single pool Kt/V, ultrafiltration percentage, body mass index, serum levels of albumin, creatinine, total iron-binding capacity, ferritin, calcium, phosphorus, bicarbonate, hemoglobin, blood white blood cells, and lymphocyte percentage. MICS, malnutrition-inflammation complex syndrome; PP, pulse pressure; SBP, systolic BP.

Figure 4.

Effect of race/ethnicity, sex, age, comorbidities, dialysis duration, and body mass index on the association between change in pulse pressure during hemodialysis and all-cause mortality. All-cause death hazard ratios (95% confidence intervals) comparing change in PP categories (Ref: ethnicity, sex, baseline age (A), presence or absence of DM, IHD, CHF (B), dialysis duration, and baseline body mass index categories (C) for SBP plus case mix plus MICS–adjusted models. The change in PP was defined as postdialysis PP minus predialysis PP. The model included adjustment for entry calendar quarter, predialysis systolic BP, age, sex, race/ethnicity, presence of diabetes mellitus, nine preexisting comorbidities, history of tobacco smoking, dialysis duration categories, primary insurance, types of vascular access, dialysis dose as indicated by single pool Kt/V, ultrafiltration percentage, body mass index, serum levels of albumin, creatinine, total iron-binding capacity, ferritin, calcium, phosphorus, bicarbonate, hemoglobin, and white blood cells, and lymphocyte percentage. CHF, chronic heart failure; Diff, difference; DM, diabetes mellitus; IHD, ischemic heart disease; MICS, malnutrition-inflammation complex syndrome; PP, pulse pressure; Ref, reference; SBP, systolic blood pressure.