Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort

Abstract

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

Fluid Overload and Inflammation Axis

“…A larger study, performed by Hung et al [23] showed significant associations between IL-6 as well as tumor necrosis factor alpha with the OH:ECW ratio in 338 CKD patients. These results were confirmed and expanded upon by an international study in 8,883 HD patients, where we observed incrementally higher CRP levels in categories of patients with progressive levels of FO using MF-BIS [10] (Fig. 1).…”

“…Recently, a 3-compartment model was developed, differentiating between fat tissue mass (FTM), lean tissue mass (LTM) and an overhydration (OH) compartment, which is calculated based on assumptions regarding the hydration of lean- and adipose tissue [15, 16], Figure1. Different cutoff levels for this compartment have been used in the literature, varying between an OH:ECW ratio of 7–15% and absolute values of OH >+1.1 or >+2.5 L [2, 10, 14, 17]. However, BIS is not the only bioimpedance (BIA)-based technology on which the assessment of fluid status in dialysis patients is based, because segmental technologies or vector plots have also been used for this purpose [13].…”

“…Various studies have reported a relation between FO and inflammation in both hemodialysis (HD) and peritoneal dialysis (PD) patients [10, 18, 19], Figure 2. Regarding the more recent studies, interleukin 6 (IL-6) levels were significantly related to the OH:ECW ratio as well as to N-terminal pro Brain Natriuretic Peptide in 57 PD patients [20].…”

“…Traditionally, the relation between FO and outcome has been explained by its cardiovascular effects [3], such as left ventricular hypertrophy, systolic dysfunction, pulmonary hypertension, and increased aortic stiffness [4-7], but recent evidence suggests that noncardiovascular factors are also of importance in further explaining the relation between FO and mortality [8, 9]. One important factor appears to be systemic inflammation [10-12]. In this short review, the relevance of association between noncardiovascular risk factors and FO, with special emphasis on inflammation, is discussed.…”

Inflammatory and Angiogenic Factors Linked to Longitudinal Microvascular Changes in Hemodialysis Patients Irrespective of Treatment Dose Intensity

“…The link between accelerated atherosclerosis and micro-inflammation has driven research in this area [10]. Uremia as a state of oxidative stress and impaired angiogenesis has been considered a promoter of micro-inflammation and endothelial dysfunction [11-13]. Micro- and macrocirculation injuries are believed to be distinct in their pathophysiology [14] however, the impact of inflammation on these processes in HD patients has not been studied in detail.…”