Overhydration, Cardiac Function and Survival in Hemodialysis Patients

PLOS ONE, Dec 2019

Background and objectives Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. Design, setting, participants and measurements A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). Results In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30–3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72–4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12–3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60–4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56–3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29–5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42–3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48–7.02 for RFO >17.4%) Cox regression analysis. Conclusions The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

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Overhydration, Cardiac Function and Survival in Hemodialysis Patients

August Overhydration, Cardiac Function and Survival in Hemodialysis Patients Mihai Onofriescu 0 1 Dimitrie Siriopol 0 1 Luminita Voroneanu 0 1 Simona Hogas 0 1 Ionut Nistor 0 1 Mugurel Apetrii 0 1 Laura Florea 0 1 Gabriel Veisa 0 1 Irina Mititiuc 0 1 Mehmet Kanbay 0 1 Radu Sascau 0 1 Adrian Covic 0 1 0 Editor: Vincenzo Lionetti , Scuola Superiore Sant'Anna, ITALY 1 1 Department of Nephrology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania, 2 Department of Cardiology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania, 3 Department of Medicine, Division of Nephrology, Koc University School of Medicine , Istanbul , Turkey Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. - In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30–3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72–4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12–3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60–4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95% CI = 1.56–3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29–5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42–3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48– 7.02 for RFO >17.4%) Cox regression analysis. Conclusions The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations. Cardiovascular events (CVE), mostly related to hypertension and left ventricular hypertrophy (LVH), are the main cause of the increased mortality observed in hemodialysis (HD) patients. Chronic subclinical volume overload occurs very frequently and may be ubiquitous in HD patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, LVH, heart failure, and eventually, higher mortality and morbidity [1]. Traditionally, “dry weight” was achieved in hemodialysis by using trial and error clinical methods [2]. However, such an empiric approach rarely solves the problems of hypertension, intradialytic hypotension and subclinical overhydration. Although probing for the lowest tolerated post-dialysis weight improved hypertension and survivalin the setting of low sodium, long-hours slow ultrafiltration dialysis [3, 4], such results are more difficult to obtain in every center, with daily standard clinical practice, and are accompanied by frequent hypotension and low quality of life [5]. Recently, bioimpedance devices have become available for routine practice, showing similar abilities in assessingan adequate “dry weight” as the probing methodperformed by the same experience Tassin clinicians [6]. Accumulating evidence suggests that a strict bioimpedance guided fluid management has a beneficial impact on blood pressure, arterial stiffness, LVH and survival [7–10]. However, the best cut-off point for defining overhydration has yet to be proved. Furthermore, different bioimpedance derived parameters have been used—absolute fluid overload (AFO), relative fluid overload (RFO), time averaged fluid overload (TAFO)–with different cut-off points being proposed to define overhydration (eg. 1.1 L for AFO, 15% for RFO) [11, 12]. Therefore, we conducted a prospective trial to investigate in a HD cohort the impact of overhydration on all-cause mortality and CVE, by using a previously reported cut-off value for overhydration (a RFO of 15%) and also investigating a new cut-off value derived from our analysis in this specific cohort. Most importantly, we aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and these outcomes is maintained when adjustments for echocardiographic parameters are considered. Methods 1. Patients The protocol of this study was approved by the Ethic (...truncated)


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Mihai Onofriescu, Dimitrie Siriopol, Luminita Voroneanu, Simona Hogas, Ionut Nistor, Mugurel Apetrii, Laura Florea, Gabriel Veisa, Irina Mititiuc, Mehmet Kanbay, Radu Sascau, Adrian Covic. Overhydration, Cardiac Function and Survival in Hemodialysis Patients, PLOS ONE, 2015, 8, DOI: 10.1371/journal.pone.0135691