Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality

Abstract

Patients receiving hemodialysis have high rates of cardiovascular morbidity and mortality that may be related to the hemodynamic effects of rapid ultrafiltration. Here we tested whether higher dialytic ultrafiltration rates are associated with greater all-cause and cardiovascular mortality, and hospitalization for cardiovascular disease. We used data from the Hemodialysis Study, an almost-7-year randomized clinical trial of 1846 patients receiving thrice-weekly chronic dialysis. The ultrafiltration rates were divided into three categories: up to 10 ml/h/kg, 10-13 ml/h/kg, and over 13 ml/h/kg. Compared to ultrafiltration rates in the lowest group, rates in the highest were significantly associated with increased all-cause and cardiovascular-related mortality with adjusted hazard ratios of 1.59 and 1.71, respectively. Overall, ultrafiltration rates between 10-13 ml/h/kg were not associated with all-cause or cardiovascular mortality; however, they were significantly associated among participants with congestive heart failure. Cubic spline interpolation suggested that the risk of all-cause and cardiovascular mortality began to increase at ultrafiltration rates over 10 ml/h/kg regardless of the status of congestive heart failure. Hence, higher ultrafiltration rates in hemodialysis patients are associated with a greater risk of all-cause and cardiovascular death.

Figure 1. Unadjusted and adjusted associations between ultrafiltration rate (UFR) and all-cause mortality based on Cox regression models

Multivariable models were adjusted for age, sex, interdialytic weight gain, race (black, non-black), smoking status (never, past, current), vintage (< 1, 1–2, 2–4, ≥ 4 years), access type (graft, fistula, catheter), systolic blood pressure (< 120, 120–140, 140–160, 160–180, ≥ 180 mm Hg), residual urine output (≤ versus > 200 ml/day), diabetes, congestive heart failure, peripheral vascular disease, ischemic heart disease, cerebrovascular disease, serum albumin, creatinine, hematocrit (< 30, 30–33, 33–36, ≥ 36%), and phosphorus, and use of α-adrenergic blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-blocker, calcium channel blocker, nitrates, and other antihypertensives. Two-way cross-product terms with time were included for albumin and systolic blood pressure due to non-proportional hazards. Abbreviations: ref., reference; CI, confidence interval; HR, hazard ratio.

Figure 2. Unadjusted and adjusted associations between ultrafiltration rate (UFR) and cardiovascular (CV)-related mortality based on Cox regression models

Multivariable models were adjusted for age, sex, interdialytic weight gain, race (black, non-black), smoking status (never, past, current), vintage (< 1, 1–2, 2–4, ≥4 years), access type (graft, fistula, catheter), systolic blood pressure (< 120, 120–140, 140–160, 160–180, ≥ 180 mm Hg), residual urine output (≤ versus > 200 ml/day), diabetes, congestive heart failure, peripheral vascular disease, ischemic heart disease, cerebrovascular disease, serum albumin, creatinine, hematocrit (< 30, 30–33, 33–36, ≥ 36%), and phosphorus, and use of α-adrenergic blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-blocker, calcium channel blocker, nitrates, and other antihypertensives. A two-way cross-product term with time was included for albumin due to non-proportional hazards. Abbreviations: ref., reference; CI, confidence interval; HR, hazard ratio.

Figure 3. Cubic spline analysis of the associations between ultrafiltration rate (UFR) and cardiovascular (CV) (solid line) and all-cause (dashed line) mortality

Hazard ratios were adjusted for age, sex, interdialytic weight gain, race (black, non-black), smoking status (never, past, current), vintage (< 1, 1–2, 2–4, ≥4 years), access type (graft, fistula, catheter), systolic blood pressure (< 120, 120–140, 140–160, 160–180, ≥ 180 mm Hg), residual urine output (≤ versus > 200 ml/day), diabetes, congestive heart failure, peripheral vascular disease, ischemic heart disease, cerebrovascular disease, serum albumin, creatinine, hematocrit (< 30, 30–33, 33–36, ≥ 36%), and phosphorus, and use of α-adrenergic blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-blocker, calcium channel blocker, nitrates, and other antihypertensives. Estimates are presented for UFRs between 5.8 ml/h/kg (the 5th percentile of observed UFR in the study sample) and 20.4 ml/h/kg (the 95th percentile).

Figure 4. Adjusted association between ultrafiltration rate (UFR) and (1) cardiovascular (CV) hospitalization and all-cause mortality, (2) CV hospitalization and CV-related mortality, and (3) CV hospitalization

Based on Cox regression models adjusted for age, sex, interdialytic weight gain, race (black, non-black), smoking status (never, past, current), vintage (< 1, 1–2, 2–4, ≥ 4 years), access type (graft, fistula, catheter), systolic blood pressure (< 120, 120–140, 140–160, 160–180, ≥ 180 mm Hg), residual urine output (≤ versus > 200 ml/day), diabetes, congestive heart failure, peripheral vascular disease, ischemic heart disease, cerebrovascular disease, serum albumin, creatinine, hematocrit (< 30, 30–33, 33–36, ≥ 36%), and phosphorus, and use of α-adrenergic blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-blocker, calcium channel blocker, nitrates, and other antihypertensives. Unadjusted estimates (not shown) for the relationship between UFR (10–13 and > 13 ml/h/kg, respectively) and outcomes were: 0.88 (0.76–1.03; P = 0.13) and 1.21 (1.05–1.40; P = 0.01) for CV hospitalization and all-cause mortality; 0.90 (0.76–1.08; P = 0.26) and 1.23 (1.05–1.45; P = 0.01) for CV hospitalization and CV-related mortality; and 0.88 (0.73–1.06; P = 0.18) and 1.14 (0.96–1.36; P = 0.13) for CV hospitalization. Abbreviations: ref., reference; CI, confidence interval.