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Hemodialysis – From Basic Research to Clinical Trials
Contributions to Nephrology
Vol. 161
Series Editor
Claudio Ronco Vicenza
Hemodialysis – From
Basic Research to
Clinical Trials
Volume Editors
Claudio Ronco Vicenza
Dinna N. Cruz Vicenza
35 figures, 2 in color, and 14 tables, 2008
Basel · Freiburg · Paris · London · New York · Bangalore ·
Bangkok · Shanghai · Singapore · Tokyo · Sydney
Contributions to Nephrology
(Founded 1975 by Geoffrey M. Berlyne)
Claudio Ronco Dinna N. Cruz
Department of Nephrology Department of Nephrology
St. Bortolo Hospital St. Bortolo Hospital
Viale Rodolfi 37 Viale Rodolfi 37
IT-36100 Vicenza (Italy) IT-36100 Vicenza (Italy)
Library of Congress Cataloging-in-Publication Data
Hemodialysis : from basic research to clinical trials / volume editors,
Claudio Ronco, Dinna N. Cruz.
p. ; cm. – (Contributions to nephrology, ISSN 0302-5144 ; v. 161)
Includes bibliographical references and indexes.
ISBN 978-3-8055-8566-8 (hard cover : alk. paper)
1. Hemodialysis. I. Ronco, C. (Claudio), 1951– II. Cruz, Dinna N. III.
Series.
[DNLM: 1. Renal Dialysis–trends. W1 CO778UN v.161 2008 / WJ 378 H4884
2008]
RC901.7.H45H448 2008
617.4⬘61059–dc22
2008015981
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and
Index Medicus.
Disclaimer. The statements, options and data contained in this publication are solely those of the individ-
ual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the
book 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.
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 change 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.
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.
© Copyright 2008 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
[Link]
Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel
ISSN 0302–5144
ISBN 978–3–8055–8566–8
Contents
IX Preface
Ronco, C.; Cruz, D.N. (Vicenza)
Dialysis Technology
1 Water Treatment for Dialysis: Technology and Clinical Implications
Hoenich, N.A. (Newcastle upon Tyne); Levin, R. (New York, N.Y.)
7 Dialysate Composition
Viganò, S.M.; Di Filippo, S.; Manzoni, C.; Locatelli, F. (Lecco)
Vascular Access
12 Challenge for the Interventional Nephrologist:
Monitoring the Arteriovenous Fistula
Campos, R.; Riella, M.C. (Paraná)
23 Preoperative Hemodialysis Fistula Evaluation: Angiography,
Ultrasonography and Other Studies, Are They Useful?
Weitzel, W.F. (Ann Arbor, Mich.)
30 Endovascular Procedures
Asif, A. (Miami, Fla.)
39 Optimal Management of Central Venous Catheters for
Hemodialysis
Canaud, B.; Chenine, L.; Henriet, D.; Leray, H. (Montpellier)
V
Epidemiology and Practice
48 Trends in Medication Use and Clinical Outcomes in
Twelve Countries: Results form the Dialysis Outcomes
and Practice Patterns Study (DOPPS)
Tentori, F. (Ann Arbor, Mich.)
55 Epigenetics and the Uremic Phenotype: A Matter of Balance
Stenvinkel, P.; Ekström, T.J. (Stockholm)
63 The Burden of Cardiovascular Disease in Patients with
Chronic Kidney Disease and in End-Stage Renal Disease
Zoccali, C. (Reggio Calabria)
Inflammation
68 BNP and a Renal Patient: Emphasis on the Unique Characteristics
of B-Type Natriuretic Peptide in End-Stage Kidney Disease
Haapio, M. (Helsinki); Ronco, C. (Vicenza)
76 Potential Interplay between Nutrition and Inflammation in
Dialysis Patients
Kuhlmann, M.K. (Berlin); Levin, N.W. (New York, N.Y.)
83 Microinflammation and Endothelial Damage in Hemodialysis
Merino, A.; Nogueras, S.; Buendía, P.; Ojeda, R.; Carracedo, J.;
Ramirez-Chamond, R.; Martin-Malo, A.; Aljama, P. (Cordoba)
89 Oxidative Stress and Anemia in Chronic Hemodialysis:
The Promise of Bioreactive Membranes
Cruz, D.N.; de Cal, M.; Ronco, C. (Vicenza)
Fluid Management
99 Consequences of Overhydration and the Need for
Dry Weight Assessment
Raimann, J.; Liu, L.; Ulloa, D.; Kotanko, P.; Levin, N.W. (New York City, N.Y.)
108 Body Composition and Outcomes in Chronic Hemodialysis Patients
Hirachan, P.; Thijssen, S.; Levin, N.W.; Kotanko, P. (New York, N.Y.)
115 Whole-Body Spectroscopy (BCM) in the Assessment of
Normovolemia in Hemodialysis Patients
Wizemann, V.; Rode, C.; Wabel, P. (Bad Homburg)
119 Blood Volume Monitoring
Winkler, R.E.; Pätow, W.; Ahrenholz, P. (Rostock)
Contents VI
Uremic Toxicity
125 From Uremic Toxin Retention to Removal by Convection:
Do We Know Enough?
Vanholder, R.; Meert, N.; Schepers, E.; Glorieux, G. (Gent)
132 Oxidative Stress in Hemodialysis
Himmelfarb, J. (Portland, Me.)
138 Determinants of Insulin Resistance and Its Effects on Protein
Metabolism in Patients with Advanced Chronic Kidney Disease
Siew, E.D.; Ikizler, T.A. (Nashville, Tenn.)
Treatment Efficacy
145 What Is Important in Dialysis? The Frequency of Treatment Sessions
Lindsay, R.M. (London, Ont.)
154 Treatment Time
Chazot, C.; Jean, G. (Tassin)
162 Membrane Characteristics
Viganò, S.M.; Di Filippo, S.; Manzoni, C.; Locatelli, F. (Lecco)
168 What Is Important in Dialysis? Efficiency: Blood Flow, KoA and Kt/V?
Gotch, F. (New York, N.Y.)
178 Cross-Membrane Flux Is a Major Factor Influencing
Dialysis Patient Outcomes
Canaud, B.; Chenine, L.; Henriet, D.; Leray, H. (Montpellier)
Advanced Techniques
185 Inflammatory Pattern in Hemodiafiltration
Panichi, V.; Paoletti, S.; Consani, C. (Pisa)
191 Online Hemodiafiltration: A Multipurpose Therapy for
Improving Quality of Renal Replacement Therapy
Canaud, B.; Chenine, L.; Henriet, D.; Leray, H. (Montpellier)
199 Biofeedback-Driven Dialysis: Where Are We?
Santoro, A.; Ferramosca, E.; Mancini, E. (Bologna)
Calcium/Phosphate Homeostasis
210 Calcium and Phosphorus Kinetics in Hemodialysis Therapy
Gotch, F. (New York, N.Y.)
Contents VII
215 Impact of Ca/P Disorders on Risks and Comorbidities
Messa, P. (Milan)
222 Diagnostic Procedures and Rationale for Specific Therapies in
Chronic Kidney Disease-Mineral and Bone Disorder
Bover, J.; Canal, C.; Marco, H.; Fernandez-Llama, P.; Bosch, R.J.;
Ballarín, J. (Barcelona)
234 Preventive Measures and New Pharmacological Approaches
of Calcium and Phosphate Disorders
Cozzolino, M.; Galassi, A.; Pasho, S., Fallabrino, G.; Gallieni, M.;
Brancaccio, D. (Milan)
Correction of Anemia
240 Insights in Anemia Management
de Francisco, A.L.M.; Piñera, C. (Santander)
247 Red Blood Cell Lifespan, Erythropoiesis and Hemoglobin Control
Kruse, A. (New York, N.Y.); Uehlinger, D.E., (Uppsala/Bern);
Gotch, F.; Kotanko, P.; Levin, N.W. (New York, N.Y.)
255 New Erythropoiesis-Stimulating Agents: How Innovative Are They?
Del Vecchio, L.; Locatelli, F. (Lecco)
261 Is the Advent of Biosimilars Affecting the Practice of
Nephrology and the Safety of Patients?
Ronco, C. (Vicenza)
271 Author Index
272 Subject Index
Contents VIII
Preface
The 17th Annual International Vicenza Course on Hemodialysis has yet
another exceptional group of speakers and we are excited that this volume of
Contributions to Nephrology is ready to guide attendees through the event and
serve as a valuable tool for the future. All contributions have been collected and
published in this volume as a result of the effort of all authors and the team of
the Department of Nephrology at San Bortolo Hospital in Vicenza.
Hemodialysis today moves towards innovative techniques, biomaterials
and devices with an absolute need for solid evidence around every new treat-
ment or technology. Based on this concept, the course and this book are
focused on innovative technology and new therapies from bench to bedside.
The continuous effort to improve patient care follows the complex pathway
from basic research to clinical trials. We have devoted a good deal of time to
the topic of uremic toxins with contributions dealing with this puzzling prob-
lem from different points of view. Other emphasized areas include cardiovas-
cular disease examined in its many facets and vascular access. As always,
significant attention is placed on the physiological undertakings of treatments.
Part of the program deals with practical questions in the dialysis unit. We are
privileged to have such a superior group of speakers who can elaborate on
these issues and discuss controversies that arise in the world of hemodialysis.
Special attention has been placed on the problems of calcium and phosphate
disorders, on the management of anemia, and finally on different biological
disorders affecting the patients on dialysis. Once more, all these aspects are
debated in light of international surveys, objective expert evaluation and recent
clinical trials.
IX
We consider this publication to be a useful supplement to the lectures pre-
sented at the three-day Vicenza course, but also a useful tool for future consul-
tation by the clinician and all who are involved in the care of hemodialysis
patients. We truly appreciate the help of the members of the faculty who have
made this possible by submitting their manuscripts in advance.
Our sincere thanks go to Anna Saccardo and Ilaria Balbo who worked in
Vicenza on the final arrangement of the course. A special thanks to Karger for
the usual outstanding quality of the publication.
We hope that the readers will enjoy the book and will consider it a com-
panion for daily clinical practice as well as for research.
Claudio Ronco Vicenza
Dinna N. Cruz Vicenza
Preface X
Dialysis Technology
Ronco C, Cruz DN (eds): Hemodialysis – From Basic Research to Clinical Trials.
Contrib Nephrol. Basel, Karger, 2008, vol 161, pp 1–6
Water Treatment for Dialysis:
Technology and Clinical Implications
Nicholas A. Hoenicha, Robert Levinb
a
School of Clinical Medical Sciences, Newcastle University, Newcastle
upon Tyne, UK, and bRenal Research Institute, New York, N.Y., USA
Abstract
The dialytic process utilizes high volumes of water in the preparation of the dialysis
fluid. Improvements in water treatment equipment have resulted in improvements in chemi-
cal quality. Awareness that endotoxin and bacterial fragments present in the water distribu-
tion loop within the dialysis, are able to cross the dialyser membrane, has resulted in an
increased focus on this aspect of water quality. Practically, the age of many water treatment
plants, extensions of distribution systems and suboptimal cleaning procedures have pre-
vented the achievement of optimal microbiological quality on a routine basis. When achieved
and maintained, clear benefits to the patient have been demonstrated. Hemodialysis
patients are also subject to increased oxidative stress which may also contribute to their mor-
bidity and mortality. Recent clinical studies using dialysis fluid made with electrolyte-
reduced water have demonstrated benefits to antioxidant status of dialysis patients, offering a
further technological solution to the problem of increased cardiovascular disease in dialysis
patients.
Copyright © 2008 S. Karger AG, Basel
Due to the increased exposure of dialysis patients to water used in the man-
ufacture of dialysis fluid, which originates as drinking water, requires additional
treatment to ensure that it meets a more stringent contaminant level content
than drinking water. The more stringent levels are embodied in national and
international standards that have evolved out of the desire to minimize the com-
plications arising from the use of inappropriate water quality.
For water used in the preparation of dialysis fluid, chemical contaminant
levels are set lower for three groups of chemical contaminants: contaminants to
which exposure is associated with clinical sequelae such as aluminum and fluo-
ride [1, 2], compounds present in the dialysis fluid (e.g. sodium), and trace metals.
Whereas there is general agreement between standards in respect of maxi-
mum permitted inorganic chemical contaminants, standards omit requirements
for organic chemical contaminants. In contrast, there is a considerable disparity
in the standards relating to the maximum level of microbiological contami-
nants. On the one hand, the United States AASI/AAMI RD 52 suggests levels
of 100 CFU/ml for bacteria and 0.25 EU/ml for endotoxin, some dialysis cen-
ters in the USA have implemented more stringent limits [3]. European Best
Practice Guidelines (EPBG) and the Italian Society of Nephrology, on the other
hand, favor the universal use of ultrapure dialysis fluid defined as containing
⬍0.1 CFU/ml for bacteria, and ⬍0.03 EU/ml for endotoxin, the latter represent-
ing the sensitivity level of currently used assays. Such fluid is further filtered in
online techniques, however, as short DNA fragments (oligodeoxynucleotides
(ODN) of 6–20 nucleotides) are able to bind to Toll-like receptors and are stim-
ulatory on immune cells, induce natural killer cell activity and induce IFN-␥,
TNF-␣, and IL-6 from mononuclear cells, even this level may in the longer
term prove to be inadequate.
The purpose of this paper is to review the water treatment technology
required to achieve a quality of water stipulated in standards and the implications
of achieving these routinely.
Water Treatment Technology
Historically, the treatment of renal failure frequently involved the use of
untreated water, however when patients were treated on a repeated basis, by the
early 1970s, it was recognized that drinking water was unsuitable for the pre-
paration of dialysis fluid and either softeners or deionizers were used [4]. Today,
the treatment that the water undergoes is much more complex as shown in
figure 1.
Essential elements of such a system are: pretreatment filtration, softeners,
carbon beds, reverse osmosis systems, ultraviolet (UV) irradiators, endotoxin
filters as well as monitors for the presence of chlorine or chloramines.
The Problem of the Distribution Loop
Whilst historically there has been emphasis on ensuring that the chemical
contaminant levels in the product water meet those specified in the standards,
the distribution loop has remained a problem. Early water distribution networks
used copper. Subsequently it was demonstrated that a leeching of copper
occurred especially in the presence of a low water pH [5]. This meant a move
Hoenich/Levin 2
Fig. 1. A panoramic view of a modern water treatment plant.
towards the use of non-toxic materials such as polyvinylchloride. When carbon
beds are used in the water treatment, water downstream of such beds does not
contain any bacteriostat (chlorine or chloramines) and is vulnerable to bacterial
proliferation. Such proliferation is hastened by the presence of low flow and
stagnation points within the distribution loop, which coupled with irregular
cleaning eventually leads to the formation of a biofilm. In view of this, dialysis
centers must have effective and regular quality control programs to ensure that
this does not happen. Furthermore, the use of water storage or holding tanks for
treated water is best avoided. When used, the tanks should have a conical or
bowl-shaped base, should drain from the lowest point of the base, incorporate a
tight-fitting lid and be vented through a hydrophobic 0.2-m air filter. Sight
tubes should be avoided due to the possible growth of algae. If an overflow pipe
is used it should be fitted with means of preventing contamination. The tank
should also be capable of disinfection.
Procedural elements – the timing and type of disinfection procedures used
for the waterline system and monitors, the timing and type of water treatment
quality control procedures – should be based on action limits and standard
operating protocols, the most important aspect being the prevention rather than
eradication. Once established the biofilm is difficult to eradicate or remove, and
acts as a source of bacterial fragments such as peptidoglycans and endotoxins
which have the potential to cross the dialysis membrane and contribute to mor-
bidity and mortality in the patient [6].
To overcome these issues, newer water treatment plants now use heat dis-
infection, a process that requires little to no rinse time and which may be used
daily to clean the distribution loop. Materials such as polyvinylchloride cannot
be used safely with heat disinfection and cross-linked polyethylene, polyvinylidene
Water Treatment for Dialysis: Technology and Clinical Implications 3
fluoride, or stainless steel (AISI type 316L) are the materials of choice. Such
materials also have a smoother internal surface, minimizing attachment of bac-
terial fragments.
Bacterial proliferation within the distribution loop can be controlled by
means other than heat. Ozonation using ozone generators are beginning to be
used. Ozone in product water may be harmful to patients, and the product
water should not be used until the ozone produced has dissipated. Further
approaches to minimize microbiological burden arising from the water use UV
irradiation and endotoxin filters. The effectiveness of UV irradiation depends
on the dose of radiant energy. A dose of 30 mW-s/cm2 will kill ⬎99.99% of a
variety of bacteria, including Pseudomonas species, in a flow-through device.
Some Gram-negative water bacteria however appear to be more resistant to
UV irradiation than others, and the use of sublethal doses of UV radiation, or
an insufficient contact time, may lead to proliferation of such bacteria in the
water system. UV irradiation at a wavelength of 254 nm converts chloramine
(NH2Cl) to chloride and ammonium ions, easily removed by reverse osmosis,
however the positioning of the unit is critical as hard water, high total dis-
solved solids, or high levels of fluoride, iodine, iron or manganese, may inter-
fere with penetration of UV irradiation through the water and inhibit
effectiveness. The radiant energy emitted by the mercury vapor lamps used
decreases with time, compromising effectiveness. Prevention of this requires
routine monitoring of the radiant energy.
UV irradiators do not eliminate bacteria and when used may even increase
endotoxin concentrations. This may be prevented by the use of an endotoxin-
retentive filter. Such filters remove endotoxins primarily by size exclusion,
although some may also remove some endotoxin by adsorption to the mem-
brane material, should be able to reduce the concentration of bacteria in the
feed water to the filter by a factor of at least 107 and that of endotoxin by a fac-
tor of at least 103. Short bacterial DNA fragments may however cross the mem-
branes used in such devices [7].
Practicality of Ensuring the Quality of Water and
Clinical Benefits
Water quality is critically dependent upon having the appropriate plant
supplemented by standard operating procedures and protocols to ensure a con-
sistent quality. The management as well as the development of such procedures
is outside the scope of this article, but guidance relating to the periodicity of
testing as well as test procedures may be found in the EBPG [8] and will be
available in the form of an international standard currently being developed
Hoenich/Levin 4
(ISO/CD 26722 – Water treatment equipment for hemodialysis applications and
related therapies).
Low levels of endotoxins and other bacterial products present in water and
dialysis fluid have been implicated as contributing to the low level microin-
flammation seen in patients undergoing regular dialysis treatment [9]. The use
of ultrapure fluids ameliorates microinflammation, reduces the severity of
long-term complications of dialysis such as malnutrition, plasma levels of
2-microglobulin, responsiveness to erythropoietin and slows loss in residual
renal function [10–13]. Some remain less convinced, possibly due to the
absence of randomized clinical studies exploring these aspects of water quality
[14, 15].
Emerging Developments in Water Treatment Technology
Active oxygen species or free radicals cause extensive oxidative damage to
biological macromolecules, contributing to disease as well as ageing. Hemodia-
lysis patients are subject to such increased oxidative stress which may con-
tribute to morbidity and mortality. When water is subject to electrolysis, the
electrical energy creates oxidized water near the anode and reduced water near
the cathode (electrolyte-reduced water). Clinical studies with electrolyte
reduced water to produce dialysis fluid have demonstrated a partial restoration
of patient antioxidant status, but such technology is only available from a single
supplier, and further long-term studies as well as costings are required before
the widespread clinical application of this novel approach [16, 17].
Conclusions
Water used in the preparation of dialysis fluid plays an important role in the
morbidity and mortality associated with regular dialysis therapy. Historically
the emphasis has been on the removal of chemical contaminants, with little
attention being paid to the microbiological quality as demonstrated in the find-
ings of several national surveys [18–20]. Although improvement of the micro-
biological quality of water has yielded a range of benefits, the dialysis patient
remains the subject of oxidative stress that can cause oxidation of biologic
macromolecules, such as low-density lipoprotein increasing adhesion of mono-
cytes to the endothelium, transformation of macrophages into foam cells and
impairment of endothelium-dependent vasorelaxation contributing to athero-
sclerosis development. The use of electrolyte-reduced water appears to offer a
promising resolution of this issue.
Water Treatment for Dialysis: Technology and Clinical Implications 5
References
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patients. Am J Kidney Dis 2005;463:16–19.
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492–497.
4 Ward RA: Water processing for hemodialysis. 1. A historical perspective. Semin Dial 1997;10:
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12 Schiffl H, Lang SM, Fischer R: Ultrapure dialysis fluid slows loss of residual renal function in
new dialysis patients. Nephrol Dial Transplant 2002;17:1814–1818.
13 Schiffl H, Lang SM, Stratakis D, Fischer R: Effects of ultrapure dialysis fluid on nutritional status
and inflammatory parameters. Nephrol Dial Transplant 2001;16:1863–1869.
14 Masakane I: Clinical usefulness of ultrapure dialysate – recent evidence and perspectives. Ther
Apher Dial 2006;10:348–354.
15 Bommer J, Jaber BL: Ultrapure dialysate: facts and myths. Semin Dial 2006;19:115–119.
16 Huang KC, Yang CC, Lee KT, Chien CT: Reduced hemodialysis-induced oxidative stress in end-
stage renal disease patients by electrolyzed-reduced water. Kidney Int 2003;64:704–5714.
17 Huang KC, Yang CC, Hsu SP, Lee KT, Liu HW, Morisawa S, Otsubo K, Chien CT: Electrolyzed-
reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease
patients. Kidney Int 2006;70:391–398.
18 Kulander L, Nisbeth U, Danielsson BG, Eriksson O: Occurrence of endotoxin in dialysis fluid
from 39 dialysis units. J Hosp Infect 1993;24:29–37.
19 Arvanitidou M, Spaia S, Askepidis N, Kanetidis D, Pazarloglou M, Katsouyannopoulos V,
Vayonas G: Endotoxin concentration in treated water of all hemodialysis units in Greece and
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Dr. Nicholas A. Hoenich
School of Clinical Medical Sciences, Newcastle University
Framington Place, Newcastle upon Tyne NE2 4 HH (UK)
Tel. ⫹44 191 6998, Fax ⫹44 191 0721, E-Mail [Link]@[Link]
Hoenich/Levin 6
Ronco C, Cruz DN (eds): Hemodialysis – From Basic Research to Clinical Trials.
Contrib Nephrol. Basel, Karger, 2008, vol 161, pp 7–11
Dialysate Composition
Sara M. Viganò, Salvatore Di Filippo, Celestina Manzoni,
Francesco Locatelli
Department of Nephrology, Dialysis and Renal Transplantation,
A. Manzoni Hospital, Lecco, Italy
Abstract
The most appropriate dialysate composition is one of the central topics in dialysis
treatment. The prescription of a certain dialysate composition could change in order to obtain
not only an adequate blood purification but also a high tolerability. Sodium balance repre-
sents the cornerstone of cardiovascular stability and good blood pressure control. The goal of
dialysis is to remove the amount that has accumulated in the interdialysis period. Potassium
removal is adequate when hyperkaliemia is avoided. Bicarbonate in dialysate should be per-
sonalized in order to avoid acidosis and end-dialysis excessive alkalosis.
Copyright © 2008 S. Karger AG, Basel
Improvements in the care of dialysis patients and in the practice of renal
transplantation have determined a dramatic increase in the number of end-stage
renal disease patients referred to renal substitutive treatments over the last
decade. The dialysis population is mainly composed of elderly and diabetic
patients with a heavy burden of co-morbid conditions, mainly related to systemic
vasculopathy and a poor performance status [1]. The choice of dialysate compo-
sition is an essential element of hemodialysis (HD) prescription, in order to
restore an adequate body electrolytic concentration and acid-base equilibrium.
Sodium
Sodium crosses the dialysis membrane by diffusion and convection. It is
well known that the sodium fractions transported by these two mechanisms are
not the same [2], and this is important in order to define intra-HD sodium
kinetics and to choose the proper dialysate sodium concentration. When
dialysate sodium activity corresponds to plasma water sodium activity multi-
plied by 0.967 (Donnan factor) (‘isonatric’ dialysate) and there is no ultrafil-
tration, the net intra-HD sodium removal is zero. Hyponatric dialysate can
theoretically be used if the patient should lose sodium by diffusion. Secondary
to the loss of sodium by diffusion, plasma osmolarity decreases with two pos-
sible side effects: (1) cellular overhydration, caused by osmotic fluid shift from
the extracellular to the intracellular compartment, which significantly con-
tributes to the so-called disequilibrium syndrome; (2) intra-HD hypotension,
caused by insufficient refilling of the intravascular compartment from the
intracellular space. Hypernatric dialysate is more frequently used in order to
avoid excessive sodium losses due to ultrafiltration and prevent cardiovascular
instability. When sodium concentration in the dialysate is higher than the
patient pre-HD blood sodium concentration, the patient is supplied with
sodium via diffusion for as long as necessary to equalize the difference in con-
centrations. In this case, the diffusive sodium transport to the patient counter-
acts the convective sodium removal due to ultrafiltration. Hypernatric dialysis
may cause insufficient net sodium removal, and consequently favor the devel-
opment of refractory hypertension. Moreover, it can trigger an intensive sense
of thirst, causing high water intake in the inter-HD interval, which has to be
treated with high ultrafiltration rates during HD which, in turn, favors
hypotensive episodes. These episodes may prevent dry body weight achieve-
ment and prompt the dialysis staff to administer hypertonic saline or to
increase dialysate sodium concentration: a vicious circle may be established,
resulting in cardiac failure and/or pulmonary edema. To be physiological,
sodium mass balance must be zero in patients in dialysis therapy; this means
that dialytic sodium removal must be equal to interdialytic sodium load. A zero
sodium balance between the intra-HD sodium removal and the inter-HD
sodium accumulation can be achieved by individualizing the dialysate sodium
concentration for each dialysis, to reach a constant end-dialysis plasma water
sodium concentration and applying a rate of ultrafiltration equal to the interdi-
alytic increase in body weight [3]. Unfortunately, this model is unsuitable for
routine use because of the need for determination of predialysis plasma water
sodium concentration at each dialysis session.
Conductivity Kinetic Modeling
The conductivity kinetic model appears to be more easily applicable,
because no blood samples or laboratory tests are needed to determine plasma
water conductivity and ionic dialysance, used in place of plasma water sodium
concentration and sodium dialysance, respectively. It has also been demonstrated
Viganò/Di Filippo/Manzoni/Locatelli 8
that this model is more accurate and precise in predicting total plasma water
sodium concentration as compared with the sodium kinetic model [4].
Potassium
In order to be adequate, potassium removal during dialysis should be equal
to the amount accumulated during the interdialytic period. Potassium removal
by dialysis is termed satisfactory if predialysis hyperkalemia is avoided, without
causing potential dangerous hypokalemia. For stable patients, a dialysate potas-
sium of 2 mmol/l is considered advisable in order to keep pre-HD plasma potas-
sium levels below 6 mmol/l. The safety of dialysate potassium concentration is
also related to the avoidance of hypokalemia and dialysis-induced arrhythmias.
Post-HD serum potassium concentration is influenced not only by the pre-HD
serum potassium concentration and the dialysate potassium concentration, but
also by plasma tonicity, changes in plasma tonicity following HD, bicarbonate
concentration and glucose in the dialysate.
Dialysate Potassium-Arrhythmia Relationship
The predialysis serum potassium concentration may play a role in certain
subsets of patients. Intra-HD serum potassium exchanges are potentially rele-
vant when they induce a certain decrease in serum potassium concentration
with each individual having a different arrhythmogenic level. It has been
demonstrated that the risk of arrhythmia is lower with a variable removal of
potassium during hemodialysis and there is no risk of a destabilizing effect on
cardiac cell [5]. Thus, potassium profiling of the dialysate may be an efficient
tool to decrease the arrythmogenic effect of HD.
Calcium
Calcium mass balance studies showed that in a patient with a normal
serum calcium before HD, dialysate calcium concentrations of 1.25 (low con-
centration) and 1.75 mmol/l (high concentration) result, respectively, in a nega-
tive and a positive intradialytic calcium balance [6], because the use of a
1.75 mmol/l calcium dialysate may constitute a strategy for improving hemo-
dynamic stability in cardiac-compromised patients. In this case, calcium salts
and vitamin D products should be used cautiously. Calcium ions play a primary
role in the contractile process of both vascular smooth muscle cells and cardiac
Dialysate Composition 9
myocytes. In patients using calcium salts as phosphate binders, it is often
advised to use low dialysate calcium concentrations to prevent or treat hyper-
calcemia [7].
Acid Buffering
The endogenous production of H⫹, mainly related to protein ingestion, is
⬃0.77 mmol/g of protein catabolized [8]. H⫹ accumulation in the blood of ure-
mic patients is buffered by plasma bicarbonate, which is used as a surrogate
marker of acidemia. A relationship between protein intake and plasma bicar-
bonate concentration, and between nutritional markers and plasma bicarbonate
concentration has been reported [9]. At least on a short-term basis, paradoxi-
cally a decrease in plasma bicarbonate level is associated with a more favorable
constellation of nutritional markers because of adequate protein intake. A
recent study evaluates the associations between baseline predialysis serum
bicarbonate and 2-year mortality [10]. They found a lower death risk for those
patients with a bicarbonate level values ⬎22 mEq/l.
The bicarbonate flux from the dialysate to the patient is determined by the
transmembrane concentration gradient, bicarbonate dialysance and treatment
time. The usual average dialysate concentration is 35 mmol/l, obtained from
proportioning dialysis stations that mix bicarbonate from solution or dry pow-
der to water and an ‘acid’ compartment containing a small amount of acetate or
lactate and sodium, potassium, calcium and magnesium. Usually, a plateau of
plasma bicarbonate is reached after 2 h of HD at an approximate value of
27–30 mmol/l.
Because of the known consequences of metabolic acidosis for the nutri-
tional status of HD patients, higher concentrations of dialysate bicarbonate
(39–48 mmol/l), resulting in a significant increase in pre-HD plasma bicarbon-
ate, have been proposed to improve the control of acidosis. This maneuver
improved protein turnover and triceps skin fold thickness, and increased serum
branched-chain amino acids, but had no effect on serum albumin and total lym-
phocyte count [11] and could cause postdialysis alkalosis.
In conclusion, acid-base status in HD patients is estimated from plasma
bicarbonate. It reflects not only protein catabolism, but also protein intake. As
long-term exposure to acidosis may alter nutritional status by enhancing pro-
tein turnover, individualization of buffer prescription is desirable in order to
avoid metabolic acidosis and post-HD alkalosis. The usual bicarbonate con-
centration in dialysate is 35 mmol/l. It should be adapted to reach midweek
pre-HD plasma bicarbonate values, from an adequately handled sample,
ⱖ22 mmol/l [12].
Viganò/Di Filippo/Manzoni/Locatelli 10
References
1 Locatelli F, Manzoni C, Del Vecchio L, Di Filippo S: Changes in the clinical condition of
haemodialysis patients. J Nephrol 1999;12(suppl 2):82–91.
2 Locatelli F, Colzani S, D’Amico M, Manzoni C, Di Filippo S: Dry weight and sodium balance.
Semin Nephrol 2001;21:291–297.
3 Gotch FA, Lam MA, Prowitt M, Keen M: Preliminary clinical results with sodium-volume model-
ing of hemodialysis therapy. Proc Clin Dial Transplant Forum 1980;10:12–17.
4 Pozzoni P, DI Filippo S, Pontoriero G, Locatelli F: Effectiveness of sodium and conductivity
kinetic models in predicting end-dialysis plasma water sodium concentration: preliminary results
of a single-center experience. Hemodial Int 2007;11:169–177.
5 Buemi M, Aloisi E, Coppolino G, Loddo S, Crascì E, Aloisi C, Barillà A, Cosentini V, Nostro L,
Caccamo C, Floccari F, Romeo A, Frisina N, Teti D: The effect of two different protocols of potas-
sium haemodiafiltration on QT dispersion. Nephrol Dial Transplant 2005;20:1148–1154.
6 Argiles A, Mourad G: How do we have to use the calcium in the dialysate to optimise the manage-
ment of secondary hyperparathyroidism? Nephrol Dial Transplant 1998;13(suppl 3):62–64.
7 Argiles A, Kerr PG, Canaud B, Flavier JC, Mion C: Calcium kinetics and the long-term effects of
lowering dialysate calcium concentration. Kidney Int 1993;43:630–640.
8 Weiner IM, Blanchard KC, Mudge GH: Factors influencing renal excretion of foreign organic
acids. Am J Physiol 1964;207:953–963.
9 Messa P, Mioni G, Maio GD, et al: Derangement of acid-base balance in uremia and under
hemodialysis. J Nephrol 2001;14(suppl 4):S12–S21.
10 Wu DY, Shinaberger CS, Regidor DL, McAllister CJ, Kopple JD, Kalantar-Zadeh K: Association
between serum bicarbonate and death in hemodialysis patients: is it better to be acidotic or alka-
lotic? Clin J Am Soc Nephrol 2006;1:70–78.
11 Oettinger CW, Oliver JC: Normalization of uremic acidosis in hemodialysis patients with a high
bicarbonate dialysate. J Am Soc Nephrol 1993;3:1804–1807.
12 K/DOQI, National Kidney Foundation: Clinical practice guidelines for nutrition in chronic renal
failure. Am J Kidney Dis 2000;35(suppl 2):1–140.
Prof. Francesco Locatelli
Department of Nephrology, Dialysis and Renal Transplantation
A. Manzoni Hospital, Via dell’Eremo 9/11
IT–23900 Lecco (Italy)
Tel. ⫹39 0341 489 850, Fax ⫹39 0341 489 860, E-Mail [Link]@[Link]
Dialysate Composition 11
Vascular Access
Ronco C, Cruz DN (eds): Hemodialysis – From Basic Research to Clinical Trials.
Contrib Nephrol. Basel, Karger, 2008, vol 161, pp 12–22
Challenge for the Interventional
Nephrologist: Monitoring the
Arteriovenous Fistula
Rodrigo Camposa, Miguel C. Riellaa,b
a
Department of Medicine, Renal Division, Evangelic School of Medicine and
b
Catholic University of Paraná, Paraná, Brazil
Abstract
Arteriovenous fistula (AVF) has been recommended as the first choice for hemodialy-
sis vascular access. This is supported by its superior patency and lower complication rates
over grafts and catheters. The increasing incidence of end-stage renal disease patients and
consequently higher prevalence of AVF in hemodialysis units have augmented the necessity
for a better understanding of AVF peculiarities. As for grafts, the K/DOQI Work Group rec-
ommends the routine use of techniques for monitoring AVF to detect dysfunctional access
with stenosis and its consequent correction in an attempt to reduce thrombotic episodes, cost
and improving quality of life of these patients. All members of a vascular access team should
be able to recognize a dysfunctional vascular access and determine the exact moment to
intervene. Particularly for the interventionist, these techniques may be used to assist percuta-
neous transluminal angioplasty, providing information about the success of the procedure
and access patency. The present article discusses the methods of AVF surveillance that are
routinely performed for hemodialysis patients with the purpose to detect stenosis, reduce
thrombosis and assist procedures.
Copyright © 2008 S. Karger AG, Basel
The native arteriovenous fistula (AVF) is regarded as the vascular access of
choice for hemodialysis (HD) because of its superior patency and lower compli-
cation rates once it has fully matured. Because of that it is recommended as the
first choice in order of placement as vascular access for HD [1, 2]. Vascular
access dysfunction is a common and daily major problem in HD units. These
complications account for 15–24% of hospitalizations in end-stage renal disease
HD patients [3] and are directly related to increased mortality because of inade-
quately delivered dialysis doses [4]. Associated to that, a thrombosed access
frequently requires an implantation of tunneled and non-tunneled catheters, in
such case increasing the risk of sepsis and morbidity [5].
As recommendation of the last two K/DOQI guidelines [1, 2], AVF preva-
lence in this decade has increased in the United States [6] and it was already the
most prevalent access in Europe and Japan [7]. This implication in AVF use will
produce clinical benefits for patients and savings in vascular access costs [8].
Despite this known superiority over arteriovenous graft (AVG) it too suffers
from frequent development of stenosis and thrombosis. For this reason, the
K/DOQI recommends programs for detection of stenosis and its consequent
correction in an attempt to reduce the event of thrombosis.
Once the AVF has matured and the patient is receiving maintenance HD,
the responsibility of AVF care and stenosis detection is referred to the dialysis
staff. However, this access care should not be transferred to only one individ-
ual, such as the nurse. Best results in detection of stenosis and prolonging
access patency are obtained when a multidisciplinary relationship among vas-
cular surgeons, nephrologists, nurses, interventional radiologists and interven-
tional nephrologists is developed [9]. The interventional nephrologist should
know how to perform and interpret methods of AVF surveillance, such as
physical examination (PE), intra-access pressure (IAP), access recirculation
and access blood flow. This knowledge promotes a correct recognition of a
dysfunctional vascular access, determines the exactly moment to correct the
stenosis and aids in the success of the procedure. The present review discusses
the methods of surveillance that are routinely performed for AVF in HD
patients.
Detection of Access Dysfunction
The fundamental idea of vascular access monitoring and surveillance is
that stenosis develops over variable intervals in the great majority of AVFs and
if detected and corrected timely, maturation can be promoted, underdialysis
minimized or avoided and thrombosis avoided or reduced [10]. As defined in
the K/DOQI vascular access guidelines, ‘monitoring’ of vascular access makes
use of PE and clinical signs to identify the access with dysfunction and the term
‘surveillance’ is referred to tests that may involve special instrumentation [2]. It
is important to emphasize that dysfunctional vascular access is not defined only
by the presence of a significant stenosis (reduction ⬎50% of normal vessel
diameter) and it should not be repaired merely because they are present.
Stenosis must be accompanied by a hemodynamic or clinical abnormality [2].
Another important point involved in the process is that every protocol must
involve multiple techniques for the detection of stenosis and in each technique
Challenge for the Interventional Nephrologist: Monitoring the AVF 13
multiple repetitive measurements must be carried out, so that inappropriate
referrals to correct stenosis are not made [10].
Monitoring
Some indirect findings may suggest the presence of stenosis. Unexplained
decreases in delivered dialysis dose, as measured by Kt/V or urea reduction
ratio, may be associated with vascular access dysfunction. An AVF which does
not support a pump flow ⬎350 ml/min, because of decreased blood flow, will
become ineffective and recirculation problems will occur. Prolonged bleeding
after removal of the needles from punctures sites may occasionally be an indi-
cator of elevated IAP (in the absence of excessive anticoagulation). These indi-
rect findings may be influenced by other factors and both are identified too late.
PE is the main part of vascular access monitoring. This method is easily
performed, non-invasive and costless. It is not useful only after maturation of
AVF, since there is evidence that proves its ability in the prediction of AVF mat-
uration [11, 12]. As soon as a non-matured AVF is identified, it can be promptly
corrected and becomes possible to puncture [13]. Evaluation of a fistula should
be performed weekly after surgery and if it fails to mature by 6 weeks, an imag-
ing study should be obtained to determine the cause of the problem as recom-
mended by the current K/DOQI Vascular Access Work Group [2].
Once it is matured, PE must be performed at least monthly and be part of
any protocol of surveillance [14]. In one study that utilized a detection protocol
of stenosis for graft and AVF, PE was included as one of the examination meth-
ods. The authors reported an isolated specificity of 95% for PE. It was not pos-
sible to identify the isolated sensitivity. The occurrence of thrombosis with
treatment by percutaneous transluminal angioplasty (PTA) was reduced from
48 to 17% after the initiation of the protocol. Only 18% of the accesses were
AVF [15]. Similarly, in another study with AVF and vascular grafts, the whole
protocol specificity was elevated (92.8%), however with low sensitivity
(35.8%). This study did not identify isolated sensitivity and specificity for PE
[16]. In another report, the accuracy in the diagnosis of stenosis in vascular
grafts was found to be 91.8% utilizing PE [17]. Recently, Asif et al. [18] exam-
ined the accuracy of PE exclusively in suspected dysfunctional AVF referred for
angiography and found a sensitivity and specificity for the outflow and inflow
stenosis of 92 and 86% and 85 and 71%, respectively. Our group evaluated the
accuracy of PE in the detection of stenosis exclusively in AVFs without a prior
screening test and found a sensitivity of 96% and specificity of 76% [19].
AVF PE begins by the anastomosis. The two most important components
of anastomosis examination is the thrill, which is an indicator of flow, and the
Campos/Riella 14
pulse, which is an indicator of downstream resistance. Another component that
can be evaluated is the bruit. Normally the thrill and bruit are prominent near
the anastomosis and they are both present in systole as well as early diastole
(continuous). The presence of stenosis reduces the blood flow and this, in turn,
reduces the strength of the thrill. If stenosis is present at a point away from the
anastomosis, the intra-access resistance rises and the flow may occur only dur-
ing systole. In this situation the thrill and bruit will be found only in systole (not
continuous). With regard to the pulse, it must be soft. If it is forceful, like a
‘water-hammer’ pulse, this often suggests the presence of stenosis. The inten-
sity of the hyperpulsatility is proportional to the severity of the stenosis.
Another step is to examine the entire length of the AV fistula. Moving up the
vein away from the anastomosis, the thrill and bruit gradually diminish. An
increase in the strength of the thrill or a new palpable thrill downstream from
the anastomotic site suggests the presence of a stenosis. The pulse should be
soft and compressible as in the anastomosis. The pulse becomes hard in the
presence of a body stenosis. An important maneuver to evaluate the pulse is to
elevate the arm above the level of the heart. Normally, the pulse may collapse
with arm elevation. If it does not, the IAP must be high and a significant steno-
sis may be the cause. In this case only the segment upstream from the stenosis
does not collapse but the downstream segment does. This is a good clue to find
the location of the stenosis.
An important cause of AVF maturation failure is the presence of accessory
veins. They must be distinguished from collateral veins, which are pathological
and develop in the presence of stenosis. The development of AV fistula depends
on the inflow pressure and the resistance of draining veins. This resistance is
decreased in the presence of side branch vessels (accessory veins), thus limiting
the maturation of the AV fistula. Accessory veins may be single or multiple, but
not all apparently decrease blood flow. When the fistula is occluded proximally,
the thrill at the fistula should disappear. If it does not, an accessory vein may be
providing an outflow channel. In this setting, palpation of the main vein below
the site of the manual occlusion will reveal a thrill at the site of the accessory
vein.
Another step is to check for pulse augmentation. With one hand, the body
of the AV fistula is manually occluded proximally and with the other hand the
pulse is palpated next to the anastomosis. With this maneuver, the pulse must
become hyperpulsatile. If the pulse augments poorly, it is an indicator of low
inflow. In this case, the arteries, anastomosis and juxta-anastomotic region
should be evaluated. In cases where the pulse is already hyperpulsatile, the
maneuver of pulse augmentation can be used to assess the severity of the steno-
sis. If there is no increase in pulse intensity, it means that the stenosis is severe,
comparable to total occlusion. In contrast, when the intensity increases, the
Challenge for the Interventional Nephrologist: Monitoring the AVF 15
stenosis must be of lesser degree. Other physical signs such as swelling in the
access arm and multiple subcutaneous collateral veins at the neck, shoulder and
upper chest are highly suggestive of central vein stenosis.
PE may assist the interventionist during PTA. Findings as non-soft palpa-
ble pulse and non-continuous thrill at anastomosis may change after a success-
ful procedure. In one report the authors concluded that the presence of a thrill
or slightly pulsatile thrill at the venous part of a dialysis graft was a good pre-
dictor of outcome after percutaneous intervention [20]. Although this study was
performed only with AVG, this information may be translated also for AVF
interventions.
Surveillance
Intra-Access Static Pressures
In AVF, the IAP falls to about 20% of the systemic arterial pressure in the
initial segment used for arterial needle puncture because of venous vessels
capacitance. However, in a well-functioning AVG, the systemic arterial pressure
is dissipated across the two anastomoses: 45% at the arterial and 25% at the
venous end. In dysfunctional AVF, the IAPs tend to be lower than in grafts,
making it more difficult to detect an appropriate increase. Notwithstanding the
differences in pressure profiles between AVF and AVG, access flow rates tend
to be quite similar when compared at similar anatomical locations [21]. When a
stenosis develops in an AVF, the IAP may be stable because collateral channels
(accessory or collateral veins) permit exit of the inflowing blood. Consequently
the flow in the upstream segment may not change. Thus, it is important to iden-
tify these side branch veins in PE. By contrast, when stenosis develops in any
segment of AVG the flow invariably decreases, because there are no collateral
channels to dissipate the inflowing blood. As discussed above, theoretical con-
siderations suggest that the measurement of IAP in AVF may not be as useful as
for AVG.
For a reliable measure of IAP it must be normalized for mean arterial pres-
sure [22]. It should be measured both in the arterial puncture site (aIAP) and
venous puncture site (vIAP), because vIAP alone may fail to detect lesions
located between the needles and in the juxta-anastomotic area and it is well
known that in ⬎70% of cases stenosis is located in these areas [23]. However,
the last K/DOQI Vascular Access Work Group does not support the use of aIAP
for use in AVF. We recently compared the results of aIAP in AVF with Doppler
ultrasound. The measurement of aIAP did not demonstrate having a good
relationship with the presence of stenosis (a sensitivity of only 60%) [19],
Campos/Riella 16
nevertheless it is important to note that measurement of aIAP was performed at
a single moment and not as multiple measurements as recommended. We
believe that IAP, measured in arterial and venous sites, is extremely important
when performed periodically and associated with other methods as PE and
blood flow [24]. Thus, IAP monitoring cannot be recommended as the only
method for surveillance of AVF at this time. Perhaps a hybrid program with
other methods may be the choice [25]. IAP performed during AVF procedural
and soon after may be useful to demonstrate a functional improvement after a
successful PTA. In AVG, IAP measurements have proved to assist in hemody-
namic assessment during angioplasty procedure [26].
IAP can be measured directly or indirectly. The indirect technique for
measuring IAP uses HD machine equipment [22]. This technique uses the
pressures from arterial pre-pump and venous post-pump drip chambers when
the blood pump is turned off. The height distance from the AVF to the upper
meniscus of the blood drip chamber is measured, converted into mm Hg
and then added to the IAP value. Nevertheless, this methodology is time-con-
suming, requiring eleven separated steps to assure accuracy [1]. To simplify
the process, the IAP can be measured directly with an aneroid pressure meter
or a digital one.
Recirculation
Measurements of recirculation become a more useful screening tool for
AVF than in AVG because blood flow in AVF, unlike AVG, can decrease to a
level less than the prescribed HD machine pump flow (⬍300 ml/min), while
maintaining access patency [27]. Because of that, this technique is not recom-
mended as a surveillance test in grafts [2]. However, up to one third of dys-
functional AVF will show an increase in recirculation that may be manifested
as a decrease in urea reduction ratio or Kt/V, but this occurs late [28, 29].
Measurement of access recirculation can be conducted using the urea-based
method or one of the non-urea methods. Nevertheless, even with ideal sample
timing and correct vein puncture, laboratory variability in urea-based mea-
surement methods will produce variability in calculated recirculation [30].
Therefore, individual recirculation values ⬍10% by using urea-based meth-
ods may be clinically unimportant. The K/DOQI Work Group does not rec-
ommend further evaluation. Values ⬎10% by using urea-based recirculation
measurement methods require investigation [2]. Other non-urea methods
seem to be more accurate in determining the exact value of recirculation as
ultrasound dilution technique [30], potassium and glucose-based dilutional
methods [31, 32].
Challenge for the Interventional Nephrologist: Monitoring the AVF 17
Blood Flow
An adequate AVF blood flow is a necessary part for a successful HD deliv-
ery dose. The volume of AVF blood flow represents the quality of a matured fis-
tula. It is important to emphasize that the quality and physical dimensions of the
artery and vein will determine the initial AVF function. If the artery is healthy,
the flow capacity of the AVF will be determined by the characteristics of the
vein used in access construction. Too small a vein will limit the flow [10]. AVFs
constructed with proximal arteries have the capacity to deliver flows higher
than distal AVFs. In general, forearm radiocephalic AVFs have flows of
600–1,000 ml/min, whereas proximal fistulas (brachiobasilic and brachio-
cephalic) have flows of 1,000–2,000 ml/min [33]. As an adequate blood flow
predicts the high quality of a matured AVF, an inadequate flow may predict its
dysfunction. It is important to emphasize that the successful maturation of AVF
may be restricted by anatomical and acquired variables as: site of anastomosis,
presence of lager diameter accessory veins, presence of disease in feeding
artery and presence of fibrotic veins, absence of patient’s ability to augment
cardiac output in response to the new AVF. Nevertheless, the most important
factor that blocks fistula maturation, reduces blood flow in a matured fistula
and predisposes to thrombosis is the development of stenosis.
In native AVFs, inadequate flow through the access, originally caused by
stenosis, is the primary functional defect that produces underdialysis and
increases the probability of thrombosis. Although there is agreement that blood
flow surveillance identifies stenosis in patients with AVF, the threshold value to
conduct an intervention is debated. The K/DOQI Work Group recommends per-
forming intervention when AVF blood flow is ⬍500 ml/min [2]. In a study with
340 AVFs comparing different values of blood flow, the best threshold for sig-
nificant stenosis diagnosis was 500 ml/min [34]. However, two other reports
found higher values for stenosis detection [35] and for prediction of AVF
thrombosis [36]. Thus, it seems that a single value may vary in different groups.
A report which measured blood flow twice monthly found that younger
patients, non-diabetics, higher systolic blood pressure and proximal AVFs were
significantly associated with higher blood flow values [37]. Probably, multiple
measurements and percent declines related to basal values offer a more realistic
prediction of fistula thrombosis.
Blood flow measurements can be performed during HD as dilution ultra-
sound and other indirect techniques or by direct techniques as duplex Doppler
ultrasound and magnetic resonance imaging [2]. However, because these last
two methods are operator-related and have equipment-related limitations,
sequential measurements have been used to detect and refer patients for inter-
ventions or predict the risk for thrombosis [38, 39]. In addition to flow
Campos/Riella 18
measurements, both duplex Doppler ultrasound and magnetic resonance imag-
ing provide anatomic assessment and direct evidence for the presence, location,
and severity of access stenosis. However, the current cost of these methods, as
well as the inability to make measurements during HD, limits their use. The cur-
rent K/DOQI Work Group indicates that there is insufficient literature evidence
to prefer one surveillance blood flow technique over the other [2].
Some studies have demonstrated the importance of blood flow surveillance
to prolong AVF patency. One study compared AVF survival in a group followed
by measurements of blood flow to another which was not. AVF thrombosis was
lower in the group of blood flow surveillance (p ⫽ 0.024) [40]. Two other stud-
ies by the same group reported that prophylactic PTA in low blood flow AVF
with diagnosis of significant stenosis improved survival of the access [41, 42].
Some information related to blood flow seems to be important for the interven-
tionist. The degree of improvement in blood flow after PTA was the only vari-
able associated with AVF patency in the same study mentioned before [42].
Following that, blood flow should be measured before and soon after an angio-
plasty, preferably by Doppler ultrasound, thus promoting valuable information
about success of the procedure. Recently, one report of 580 PTAs in 190 AVFs
found a significant negative correlation between the degree of stenosis and the
preangioplasty blood flow. The only variable that correlated negative with
postangioplasty blood flow was the number of stenosis in the same access [43].
Despite the recommendation of surveillance in AVF with the aim of reduc-
ing thrombosis, based on the above studies [2], some controversy has ques-
tioned the beneficial use of blood flow to reduce costs. One study noted that
healthcare costs in HD patients with permanent access was reduced after imple-
mentation of blood flow surveillance, nevertheless the benefit was seen only for
patients with AVG [44]. Another similar study demonstrated a reduction in cost,
thrombosis, hospitalization and catheter placement for AVG as well as for AVF
[45]. A report that tried to find the most economic blood flow threshold noted
no benefits for both values when compared to no screening scenario [46].
However it is important to keep in mind that any preventive exposure to
catheters will improve HD patients’ healthcare and reduce morbidity.
Conclusion
Routine use of monitoring and surveillance methods for AVF such as PE
and measurements of IAP and blood flow will reduce thrombosis and will
improve quality of life in HD patients. All members of vascular access teams
mostly recognize and interpret the findings of these techniques. Specifically,
interventionists should interpret these methods just before and soon after the
Challenge for the Interventional Nephrologist: Monitoring the AVF 19
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