Rapid Fluid Removal During Dialysis is Associated With Cardiovascular Morbidity and Mortality

Jennifer E Flythe; Stephen E Kimmel; Steven M Brunelli

Disclosures

Kidney Int. 2011;79(2):250-257. 

In This Article

Abstract and Introduction

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.

Introduction

The United States is home to more than 350,000 hemodialysis (HD) patients.[1] Dialysis patients experience high rates of mortality, driven largely by an exceptionally high rate of cardiovascular (CV)-related mortality, which exceeds that of the general population by 10- to 20-fold.[2,3] Dialysis patients have a high prevalence of traditional CV risk factors such as diabetes and hypertension, as well as a number of additional risk factors related to their kidney dysfunction and/or to the dialytic procedure such as autonomic dysfunction, vascular calcification and stiffness, and increased levels of circulating inflammatory mediators.[1,4,5] Unfortunately, many of these factors have proven to be either non-modifiable or difficult to modify within the scope of current dialytic practice.

One compelling and potentially modifiable putative CV risk factor is ultrafiltration rate (UFR; the rate at which fluid is removed during the course of dialysis). As native kidney function wanes, ultrafiltration is necessary to maintain volume control (i.e., salt and water balance), but it simultaneously and disadvantageously promotes non-physiological fluid shifts and hemodynamic instability. In turn, these factors contribute to tissue ischemia, maladaptive cardiac structural changes, myocardial stunning, arrhythmia, and cardiac sudden death.[6–14] Despite obvious biological plausibility, the association between UFR and CV morbidity and mortality has not been well studied. The only previous study in this regard examined UFR >10 (versus ≤10) ml/h/kg, showing a small increase in all-cause mortality (adjusted RR=1.09; P=0.02) but no increase in cardiopulmonary mortality (adjusted RR=1.04; P=0.41).[15] Subsequent data suggest that the cut point of 10 ml/h/kg may have been too low to observe a true UFR–CV mortality association,[16] and the issue remains unsettled.

Therefore, we undertook this study in order to clarify the associations between UFR and both all-cause and CV-related mortality among patients undergoing chronic, thrice-weekly HD. We hypothesized that higher UFR would be associated with greater CV-related mortality that, in turn, would drive all-cause mortality. We used the data from the Hemodialysis Study (HEMO), as this study is one of very few large-scale prospective studies in chronic dialysis patients in which the CV outcomes were rigorously adjudicated according to standardized criteria.[17] Moreover, we sought to leverage these data to identify a threshold at which higher UFR may be detrimental to CV health and survival.

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