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      Dialysis Dose and Intradialytic Hypotension: Results from the HEMO Study

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          Abstract

          Background: Intradialytic hypotension (IDH) is common and is associated with increased morbidity and mortality in chronic hemodialysis patients. A higher dialysis ‘dose' may generate transient intradialytic osmotic gradients, predisposing to intracellular fluid shifts and resulting in hypotension. Study Design: We performed a post hoc analysis of the HEMO study, a multicenter trial that randomized chronic hemodialysis patients to high versus standard Kt/V and higher versus lower membrane flux. In order to achieve dose targets, per protocol, adjustments were made in membrane efficiency, blood flow or dialysate flow before changing session length. Detailed hemodynamic and urea kinetic modeling data were abstracted from 1,825 individuals. The primary outcome was the occurrence of hypotensive events necessitating clinical intervention (saline infusion, lowering of ultrafiltration rate or reduced blood flow). Results: Intradialytic hypotensive events occurred more frequently in the higher-Kt/V group (18.3 vs. 16.8%; p < 0.001). Participants randomized to higher-target Kt/V had a greater adjusted risk of IDH than those randomized to standard Kt/V [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.01-1.25]. Higher vs. lower dialyzer mass transfer-area coefficient for urea and rate of urea removal were associated with greater adjusted odds of IDH (OR 1.15; 95% CI 1.04-1.27 and OR 1.05; 95% CI 1.04-1.06 per mg/dl/h, respectively). Conclusions: Higher dialysis dose, at relatively constrained treatment times, may associate with an increased risk of IDH. These findings support the possibility that rapidity of intradialytic reductions in plasma osmolality may play an important role in mediating hemodynamic instability during dialysis.

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          Most cited references37

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          Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients.

          The relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multicenter prospective cohort study to evaluate the impact of hemodialysis-associated hypotension on mortality. We recruited 1244 patients (685 males; mean age, 60 +/- 13 years) who underwent hemodialysis in 28 units during the two-year study period beginning in December 1999. Pre-, intra-, and postdialysis BP, and BP upon standing soon after hemodialysis, were measured in all patients at entry. Logistic regression analysis was used to assess the effect on mortality of pre-, intra-, and postdialysis BP, a fall in BP during hemodialysis, and a fall in BP upon standing soon after hemodialysis. During the study period, 149 patients died. Logistic models identified the lowest intradialysis systolic blood pressure (SBP) and degree of fall in SBP upon standing soon after hemodialysis as significant factors affecting mortality, but not pre- or postdialysis SBP and diastolic BP. The adjusted odds ratio for death was 0.79 (95% CI 0.64-0.98) when the lowest intradialysis SBP was analyzed in increments of 20 mm Hg, and was 0.82 (95% CI 0.67-0.98) when the fall in SBP upon standing soon after hemodialysis was analyzed in increments of 10 mm Hg. These results suggest that intradialysis hypotension and orthostatic hypotension after hemodialysis are significant and independent factors affecting mortality in hemodialysis patients.
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            Intradialytic hypotension and vascular access thrombosis.

            Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.
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              Haemodialysis-Induced Myocardial Stunning in Chronic Kidney Disease – A New Aspect of Cardiovascular Disease

              Chronic haemodialysis (HD) patients are already primed by a large number of structural and functional peripheral vascular and cardiac abnormalities to experience demand myocardial ischaemia. Transient myocardial ischaemia may lead to left ventricular (LV) dysfunction that can persist after the return of normal perfusion. This prolonged dysfunction is known as myocardial stunning. Repetitive episodes of ischaemia can be cumulative and have been shown to lead to prolonged LV dysfunction (in patients with ischaemic heart disease). Conventional HD itself is a sufficient cardiovascular functional stressor to precipitate such recurrent ischaemic insults, leading to myocardial functional and structural changes, eventually resulting in fixed systolic dysfunction and heart failure (conferring a dismal prognosis for patients undergoing dialysis). Furthermore these same haemodynamic insults may also adversely affect other vascular beds in other vulnerable organ systems, driving an even wider range of pathophysiological processes. A variety of therapeutic manoeuvres aimed at improving the haemodynamic tolerability of treatment have been shown to reduce acute dialysis-induced myocardial ischaemia. This article aims to give an appreciation of the possibility that modification of the dialysis treatment to improve tolerability of therapy may have the potential to provide us with additional therapeutic targets, to reduce currently excessive rates of cardiovascular morbidity and mortality.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2013
                November 2013
                26 October 2013
                : 38
                : 5
                : 388-396
                Affiliations
                aRenal Division and bDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and cHarvard Medical School, Boston, Mass., USA
                Author notes
                *Finnian Mc Causland, MB, MMSc, MRB-4, Brigham and Women's Hospital, Boston, MA 02446 (USA), E-Mail fmccausland@partners.org
                Article
                355958 PMC3904183 Am J Nephrol 2013;38:388-396
                10.1159/000355958
                PMC3904183
                24192428
                6a47f1c4-f35c-4bd5-b016-bd3d37070197
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 29 May 2013
                : 20 September 2013
                Page count
                Figures: 1, Tables: 4, Pages: 9
                Categories
                Original Report: Patient-Oriented, Translational Research

                Cardiovascular Medicine,Nephrology
                Urea reduction,HEMO study ,Hemodialysis,Osmolality,Intradialytic hypotension

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