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Nephrology Dialysis Transplantation (NDT) is the official publication of the European Renal Association – European Dialysis and Transplantation Association (ERA-EDTA).NDT is one of the world’s leading journals devoted to original clinical and laboratory research in nephrology, dialysis, and transplantation, providing an essential resource for researchers and clinicians throughout the world. ERA-EDTA is Europe’s largest association of nephrologists and all members receive a copy of the journal as part of their subscription.

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Impact Factor: 3.396Ranking: 7/24 Si: Transplantation 15/73 Si: Urology & Nephrology 2011 Journal Citation Reports® (Science Citation Index, ISI)

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Offi cial Publication of the European Renal Association -European Dialysis and Transplant Association

Paris, 2012, ERA-EDTA.

ISSN 0931-0509 (Print) ISSN 1460-2385 (Online)

Volume 27 Number 7 July 2012

www.ndt.oxfordjournals.org

ndtNEPHROLOGY DIALYSIS TRANSPLANTATION

Basic and clinical renal science

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umber 7 July 2012 pages 2607–3001

2013 Schedule

28/1 January 11 December 2012 22 January 2013

28/2 February 09 January 2013 18 February 2013

28/3 March 01 February 2013 12 March 2013

28/4 April 07 March 2013 15 April 2013 ERA - EDTA 18 - 21 May Istanbul

World Congress of Nephrology 31 May - 4 June Hong Kong

28/5 May 08 April 2013 14 May 2013

28/6 June 08 May 2013 12 June 2013

28/7 July 07 June 2013 12 July 2013

28/8 August 10 July 2013 14 August 2013

28/9 September 07 August 2013 13 September 2013 ASN 5 - 10 November Atlanta

28/10 October 09 September 2013 11 October 2013

28/11 November 10 October 2013 14 November 2013

28/12 December 07 November 2013 11 December 2013

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Paris, 2012, ERA-EDTA.


Volume 27 Number 7 July 2012




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Abstracts




Volume 27 Number S2 May 2012



Editorial Review

What can the dialysis physician learn from kinetic modellingbeyond Kt/Vurea?

Sunny Eloot1*, Daniel Schneditz2,* and Raymond Vanholder1

1Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Gent, Belgium and 2Institute of Physiology,Medical University of Graz, Graz, Austria

Correspondence and offprint requests to: Sunny Eloot; E-mail: [email protected]*These authors equally contributed to this publication.

Keywords: compartments; distribution volume; kinetics; middlemolecules; protein-bound; small solutes

The importance of dialysis kinetic modelling

Although patients with renal failure retain a large varietyof solutes, Kt/Vurea is the most widely applied marker forthe adequacy of dialysis. The popularity of Kt/Vurea isprobably related to its simple calculation from pre- andpost-dialysis urea concentrations avoiding formal kineticmodelling [1, 2], and on the ease with which urea concen-trations can be determined in most laboratories. Using thisapproach, the calculation is based on simple equationswhich provide corrections for urea generation, volumecontraction, convective clearance and compartmenteffects.

While insufficient urea removal has been related tomorbidity and mortality of dialysis patients in several un-controlled studies [3–5], two controlled studies showedthat increasing dialysis dose, defined as a higher Kt/Vurea,did not improve survival [6, 7]. Hence, it might be con-sidered that other factors play an equal, if not more impor-tant, role in the pathophysiological deterioration ofpatients with renal dysfunction, and that the focus on ureakinetics alone is not representative for the evolutionduring dialysis of most other uraemic solutes. Evidence ofthe biochemical impact of urea at concentrations found inuraemia is scanty. In addition, cell membranes are highlypermeable to urea so that intradialytic shifts from intra- toextracellular spaces are easier than for most other solutes.Moreover, urea is not protein-bound which is in contrastto many other uraemic retention solutes. Hence, knowl-edge of the kinetics of other than urea may significantlyhelp to understand the evolution of solutes during dialysisand to unravel how dialysis adequacy could be increasedwith regard to pathophysiologically important solutesother than urea.

The general perception is that dialysis kinetic modellingis a highly abstract research topic for mathematicians,sitting somewhere in an office far from the patient’s

bedside and from practical application. However, kineticmodelling can be of superior help to improve dialysis ade-quacy. This overview will essentially focus on the addedvalue of kinetic modelling in clinical practice. We willfirst focus on the basis as well as the different approachesthat can be applied to dialysis kinetic modelling. Sub-sequently, the kinetics of several uraemic solutes, otherthan urea, will be discussed to show that dialysis kineticsbeyond Kt/Vurea may help to understand dialysis and toapply this knowledge with the aim to improve patientoutcomes.

Different approaches of dialysis kinetic modelling

In general, kinetics describe the variation over time of aphysical entity (e.g. concentration, mass, energy) which isexchanged among different systems or in between asystem and the environment. This dynamic process isgoverned by driving forces (e.g. concentration gradients).The human body can be considered as comprising of

different anatomical compartments separated by semi-per-meable membranes. Approximately 58% of the body con-sists of water divided over intra- and extracellularcompartments. The latter corresponds to the sum ofplasma and interstitial water. Transport between compart-ments occurs passively by free diffusion of uncharged(e.g. water, oxygen, urea) or charged particles (ions, e.g.Na+,HCO�

3 ), and by diffusion via carriers or channels.Next to a passive concentration-driven process, transportalso occurs as an active process where energy is suppliedby ATP (adenosine triphosphate), or as secondary activetransport according to an electrochemical gradient.To mathematically describe these processes, the body

can be divided into different compartments in which thephysical entity of interest (e.g. concentration) is con-sidered to assume the same value over the compartmentvolume. In most cases, a mechanistic model with alimited number of compartments is sufficient to describesolute kinetic behaviour during dialysis. The advantage of

© The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.For Permissions, please e-mail: [email protected]

Nephrol Dial Transplant (2012) 0: 1–9doi: 10.1093/ndt/gfs367

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Nephrology Dialysis Transplantation - OUP · PDF fileNephrology Dialysis Transplantation ndt.oxfordjournals.org Contact us for more information: t: +44 (0) 1865 355 190 e: [email protected]