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Continuous-Equivalent Urea Clearances EKR and Stdk As Dose Measures in Intermittent Hemodialysis AARNE VARTIA

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Continuous-Equivalent Urea Clearances EKR and Stdk As Dose Measures in Intermittent Hemodialysis AARNE VARTIA AARNE VARTIA AARNE VARTIA Acta Universitatis Tamperensis 2154 Continuous-Equivalent Urea Clearances EKR and stdK as Dose Measures in Intermittent Hemodialysis AARNE VARTIA Continuous-Equivalent Urea Clearances EKR and stdK as Dose Measures in Intermittent Hemodialysis AUT 2154 AUT AARNE VARTIA Continuous-Equivalent Urea Clearances EKR and stdK as Dose Measures in Intermittent Hemodialysis ACADEMIC DISSERTATION To be presented, with the permission of the Board of the School of Medicine of the University of Tampere, for public discussion in the small auditorium of building M, Pirkanmaa Hospital District, Teiskontie 35, Tampere, on 22 April 2016, at 12 o’clock. UNIVERSITY OF TAMPERE AARNE VARTIA Continuous-Equivalent Urea Clearances EKR and stdK as Dose Measures in Intermittent Hemodialysis Acta Universitatis Tamperensis 2154 Tampere University Press Tampere 2016 ACADEMIC DISSERTATION University of Tampere, School of Medicine Savonlinna Central Hospital Finland Supervised by Reviewed by Professor emeritus Jukka Mustonen Docent Risto Ikäheimo University of Tampere University of Oulu Finland Finland Docent Kaj Metsärinne University of Helsinki University of Turku Finland The originality of this thesis has been checked using the Turnitin OriginalityCheck service in accordance with the quality management system of the University of Tampere. Copyright ©2016 Tampere University Press and the author Cover design by Mikko Reinikka Distributor: [email protected] https://verkkokauppa.juvenes.fi Acta Universitatis Tamperensis 2154 Acta Electronica Universitatis Tamperensis 1653 ISBN 978-952-03-0082-1 (print) ISBN 978-952-03-0083-8 (pdf) ISSN-L 1455-1616 ISSN 1456-954X ISSN 1455-1616 http://tampub.uta.fi Suomen Yliopistopaino Oy – Juvenes Print Tampere 2016 441 729 Painotuote Dedicated to my wife Ansa, a Very Important Person CONTENTS Abstract ........................................................................................................................................ 8 Tiivistelmä ................................................................................................................................. 11 LIST OF ORIGINAL COMMUNICATIONS ................................................................. 15 ABBREVIATIONS AND DEFINITIONS ....................................................................... 16 1 INTRODUCTION ........................................................................................................ 18 2 REVIEW OF THE LITERATURE ........................................................................... 20 2.1 Uremic syndrome ................................................................................................ 20 2.1.1 Water and sodium .................................................................................... 20 2.1.2 Acidosis ..................................................................................................... 21 2.1.3 Anemia and endocrine disturbances ..................................................... 21 2.1.4 Urea ............................................................................................................ 21 2.1.5 Uremic toxins ........................................................................................... 22 2.1.6 Causes of death ........................................................................................ 24 2.2 Blood purification techniques ............................................................................ 24 2.2.1 Diffusion and convection ....................................................................... 24 2.2.2 Adsorption and ion exchange ................................................................ 25 2.3 Hemodialysis prescription .................................................................................. 25 2.3.1 Dialysate composition and temperature ............................................... 25 2.3.2 Filter and convection technique ............................................................ 25 2.3.3 Blood, dialysate, and filtrate flow .......................................................... 26 2.3.4 Duration and frequency .......................................................................... 27 2.3.5 Water removal .......................................................................................... 27 2.3.6 Prescribed and delivered dose................................................................ 27 2.4 Delivered dose ...................................................................................................... 29 2.4.1 Marker solutes .......................................................................................... 29 2.4.2 Concentration and clearance .................................................................. 30 2.4.3 Single-pool UKM ..................................................................................... 30 2.4.4 Double-pool UKM .................................................................................. 32 2.4.5 eKt/V ........................................................................................................ 34 2.4.6 Direct dialysis quantification (DDQ).................................................... 35 2.4.7 Online monitoring ................................................................................... 35 2.4.8 Residual renal function............................................................................ 36 2.5 Continuous-equivalent clearance (ECC) .......................................................... 37 2.5.1 Aiming at a universal dose measure ...................................................... 37 2.5.2 Definitions based on UKM .................................................................... 37 2.5.3 Simple equations ...................................................................................... 39 2.5.4 Guidelines ................................................................................................. 40 2.6 Dependence of outcome on dose (adequacy) ................................................. 40 2.6.1 Session dose .............................................................................................. 40 2.6.2 Treatment duration .................................................................................. 41 2.6.3 Treatment frequency ............................................................................... 42 2.6.4 Scaling ........................................................................................................ 44 2.6.5 Residual renal function ........................................................................... 45 2.6.6 Continuous-equivalent clearance ........................................................... 45 2.6.7 Overdialysis ............................................................................................... 46 2.6.8 Soft endpoints .......................................................................................... 47 3 AIMS OF THE STUDY ............................................................................................... 49 3.1 Is high mortality in hemodialysis due to low dose?........................................ 49 3.2 How should the dialysis dose be measured? ................................................... 49 3.3 How could dosing be improved? ...................................................................... 49 4 SUBJECTS AND METHODS .................................................................................... 50 4.1 Patients .................................................................................................................. 50 4.1.1 Hemodialysis treatment periods and modeling sessions ................... 50 4.1.2 Dialysis prescriptions .............................................................................. 52 4.1.3 Data collection ......................................................................................... 52 4.2 Calculations ........................................................................................................... 52 4.2.1 Urea kinetic modeling ............................................................................. 52 4.2.2 Simulation and automation .................................................................... 54 4.2.3 HEMO-equivalent EKR/V and stdK/V ............................................ 54 4.2.4 Anthropometric normalization of ECC ............................................... 55 4.3 Computer applications ........................................................................................ 55 4.4 Statistical methods ............................................................................................... 56 4.5 Ethical aspects ...................................................................................................... 56 5 RESULTS ......................................................................................................................... 57 5.1 Effect of frequency (I FREQUENCY) ........................................................... 57 5.1.1 Effect on measures of dialysis dose ...................................................... 57 5.1.2 Effect on required treatment time ........................................................ 58 5.1.3 Effect on concentrations ........................................................................ 59 5.2 Effect of residual renal function (II INCREMENTAL) .............................. 61 5.2.1 Effect on required treatment time ........................................................ 61 5.2.2 Effect on
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