Measuring Fluid Overload and Mortality Risk in ESRD Patients

Nisha Bansal, MD, MAS


June 22, 2017

Fluid overload, or hypervolemia, is a common complication of kidney disease, particularly in patients with end-stage renal disease (ESRD) on hemodialysis. It is associated with a higher burden of symptoms, poor physical functioning, and the need for more frequent dialysis. Fluid overload remains a challenge to diagnose, as traditional clinical parameters are often subjective or difficult to interpret in the setting of kidney disease.

Bioimpedance spectroscopy (BIS) is a noninvasive, inexpensive, and portable method that has been used for body composition analysis.[1] It determines the electrical impedance, or opposition to the flow of an electric current through body tissues, which can then be used to estimate body composition, including total body water, intracellular volume, and extracellular volume.

Study Summary

A recent study published in the Journal of the American Society of Nephrology examined the association between fluid overload, as assessed by BIS, and risk of mortality among 39,566 incident hemodialysis patients from 26 countries.[2] Patients had BIS measured within 3 months of dialysis initiation and were followed longitudinally on average for 497 days.

There was a wide distribution of volume status at the start of the study ranging from -0.1 L (10th percentile) to 6.1 L (90th percentile), with a mean of 2.7 L of volume excess. Fluid overload was defined as ≥ 15% in men and ≥ 13% in women of fluid excess in relation to the extracellular volume (which corresponds to absolute fluid overload of 2.5 L). The investigators found that fluid overload at baseline was significantly associated with greater risk of mortality, even accounting for important patient characteristics. Furthermore, this association was seen across categories of predialysis systolic blood pressure, where the association of fluid overload with mortality was greatest in those with low (< 130 mm Hg) and high (≥ 160 mm Hg) predialysis systolic blood pressure.

The investigators also examined the association of cumulative fluid overload over 1 year and risk of subsequent mortality. Cumulative fluid overload was assessed by longitudinal BIS measures and calculating area-under-the-curve over 1 year among survivors. The associations between cumulative fluid overload with mortality were even stronger than that seen with baseline measures of fluid overload. This association was consistent across at levels of predialysis systolic blood pressure but was strongest among patients with a predialysis systolic blood pressure < 130 mm Hg. The authors concluded that chronic fluid overload is an important risk factor for mortality in patients on hemodialysis.[2]

Fluid Volume Management

The association between fluid overload as assessed by bioimpedance and long-term outcomes has been evaluated in a few prior studies as well. Among smaller populations of prevalent hemodialysis patients, fluid overload (also assessed by BIS) has been shown to be associated with a two- to threefold increased risk of total mortality.[3,4] In a study of over 3000 prevalent dialysis patients, greater fluid overload (measured by bioimpedance analysis [BIA], which is similar to BIS) was significantly associated with greater risk of mortality.[5]

Given the importance of management of fluid overload, a few small studies have utilized bioimpedance to guide fluid volume management in dialysis patients. In a randomized clinical trial of 156 hemodialysis patients, fluid management using BIA measures led to regression of left ventricular mass, decrease in blood pressure, and improvement in arterial stiffness.[6] In a prospective study of 55 hemodialysis patients over 3 months, active fluid management guided by BIA was associated with improved fluid status and blood pressure.[7]

Application of diagnostic tools such as BIS may be a novel approach to an established but challenging clinical problem of volume management in dialysis patients. Further larger pragmatic studies would be valuable to determine whether bioimpedance to guide volume management improves patient-reported outcomes as well as long-term clinical outcomes in the high-risk hemodialysis population.

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