Table Of ContentNEW PERSPECTIVES IN
HEMODIALYSIS,
PERITONEAL DIALYSIS,
ARTERIOVENOUS
HEMOFILTRATION, AND
PLASMAPHERESIS
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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NEW PERSPECTIVES IN HEMODIALYSIS, PERITONEAL DIALYSIS,
ARTERIOVENOUS HEMOFILTRATION, AND PLASMAPHERESIS
Edited by W. H. Horl and P. J. Schollmeyer
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NEW PERSPECTIVES IN
HEMODIALYSIS,
PERITONEAL DIALYSIS,
ARTERIOVENOUS
HEMOFILTRATION, AND
PLASMAPHERESIS
Edited by
W. H. Horl and
P. J. Scholhneyer
Medizinische UniversitiUsklinik
Freiburg, Federal Republic of Germany
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
International Symposium on New Perspectives in Hemodialysis, Peritoneal Dialysis,
Arteriovenous Hemofiltration, and Plasmapheresis (1988: Freiburg, Germany)
New perspectives in hemodialysis, peritoneal dialysis, arteriovenous hemofiltration, and
plasmapheresis I edited by W. H. Horl and P. J. Schollmeyer.
p. em. - (Advances in experimental medicine and biology; v. 260)
Proceedings of an International Symposium on New Perspectives in Hemodialysis,
Peritoneal Dialysis, Arteriovenous Hemofiltration, and Plasmapheresis, held October 6-8,
1988, in Freiburg, Federal Republic of Germany" - T.p. verso.
Includes bibliographical references.
L Hemodialysis-Congresses. 2. Peritoneal dialysis-Congresses. 3. Continuous arterio
venous hemofiltration-Congresses. 4. Plasmapheresis-Congresses. I. Horl, Walter H. II.
Schollmeyer, P. J. III. Title. IV. Series.
[DNLM: 1. Hemodialysis-congresses. 2. Hemofiltration-congresses. 3. Peritoneal
Dialysis-congresses. 4. Plasmapheresis-congresses. WJ 378 I5993nJ
RC901.7.H45I575 1988
617.4'61059-dc20
DNLM/DLC 89-22951
for Library of Congress CIP
ISBN-13:978-1-4684-5720-9 e-ISBN-13:978-1-4684-5718-6
001: 10.1007/978-1-4684-5718-6
Softcover reprint of the hardcover 1s t edition 1989
Proceedings of an International Symposium on New Perspectives in
Hemodialysis, Peritoneal Dialysis, Arteriovenous Hemofiltration,
and Plasmapheresis, held October 6-8, 1988, in Freiburg,
Federal Republic of Germany
© 1989 Plenum Press, New York
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
We are pleased to present our readers the Proceedings of the
International Symposium "New Perspectives in Hemodialysis,
Peritoneal Dialysis, Arteriovenous Hemofiltration, and Plasma
pheresis" which was held in Freiburg i. Br. (FRG) during Oct
tober 6-8, 1988.
The meeting was held on the occasion of opening the new
dialysis unit of the University Hospital of Freiburg i. Br ..
The topics discussed included membrane biocompatibility,
catabolic factors associated with dialysis therapy, phar
macological therapy in dialyzed patients, erythropoietin and
renal anemia, new developments in CAVH, CAPD and
plasmapheresis, renal replacement therapy in acute renal
failure, and plasmapheresis therapy in systemic diseases. It
was unfortunately impossible in this volume, to include the
extended, lively and stimulating discussions which were
enjoyed by the participants during the conference.
The meeting has provided an unique framework for close
interaction between scientists from various disciplines,
including nephrology, pharmacology, hematology, cardiology,
anesthesiology, surgery, intensive care medicine, and patho
logy.
We would like to express our gratitude and appreciation for all
those who have stimulated, encouraged and supported us to hold
the symposium in Freiburg. This endeaver could not have been
possible without the generous financial support of Asid-Bonz
(BOblingen), Bayer AG (Leverkusen), Bayropharm GmbH (Koln),
Baxter (Munchen), Ciba-Geigy (Wehr/Baden), Cilag GmbH
(Sulzbach), Fresenius AG (Oberursel), Gambro (Martinsried),
Gry~Pharma GmbH (Kirchzarten), Hoechst AG (Frankfurt), Hospal
(Nurnberg), Knoll AG (Ludwigshafen), Lederle-Cyanamid
(Wolfratshausen), E. Merck (Darmstadt), MSD Sharp and Dohme
GmbH (Munchen), Pfizer GmbH (Karlsruhe), and pfrimmer and Co
(Erlangen) .
We are indepted to Dr. Jutta Steinbiss, MSD Sharp and Dohme
GmbH (Munchen) and Mrs. S. Werth, Hagen GmbH-Kongress-Service
for their advice and practical help and to Mrs. I. Szkibik,
Mrs. I. Goldbeck, Miss R. Vogel, Miss P. Damisch for their
invaluable assistance and help in the organization of the
meeting.
v
CONTENTS
I NEW PERSPECTIVES IN HEMODIALYSIS
Protein catabolic factors in patients on renal
replacement therapy .............................. 1
J. Bergstrom
~2 Microglobulin-derived amyloid in dialysis
patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 11
E. Ritz, R. Deppisch, and G. Stein
Mechanisms and consequences of complement activation
during hemodialysis .............................. 19
M.D. Kazatchkine, and N. Haeffner-Cavaillon
Neutrophil activation during hemodialysis .............. 27
M. Haag-Weber, P. Schollmeyer, and W.H. Horl
Biocompatibility - a system approach 39
H. Klinkmann, and D. Falkenhagen
Treatment of uremic anaemia with recombinant
human erythropoietin ............................ 53
C. Ponticelli, S. Casati, and M. Campise
Endocrine abnormalities in patients with
endstage renal failure ........................... 61
F. Kokot, A. Wiecek, W. Grzeszczak, J. Klepacka,
M. Klin, and M. Lao
Carnitine supplementation in uremia .................... 69
P. Furst, A. Gloggler, and C. RossIe
II PHARMACOLOGICAL THERAPY IN DIALYZED PATIENTS
Pathophysiology and treatment of hypertension
in dialysis patients ............................. 79
A. Heidland, and R.M. Schaefer
Adjustment of drug dosage to hemodialysis
patients ......................................... 93
F. Keller, U. Kunzendorf, H. Hilt,
and A. Schwarz
vii
Pharmacokinetic aspects of drug transport in con-
tinuous ambulatory peritoneal dialysis ........... 105
N. Lameire, and S. Ringoir
Drug therapy during continuous arteriovenous
hemofil tration ................................... 117
E. Keller
III NEW PERSPECTIVES IN PERITONEAL DIALYSIS
The biology of the peritoneal membrane during
chronic peritoneal dialysis ...................... 129
H.A. Verbrugh
Lymphatic absorption during peritoneal
dialysis ......................................... 135
K.D. Nolph
CAPD with bicarbonate solution ......................... 139
M. Feriani, and G. La Greca
Glucose polymer as an osmotic agent in CAPD ............ 149
C.D. Mistry, and R. Gokal
Effects of long-term treatment with human
recombinant erythropoietin in
patients on CAPD ................................. 157
H.B. Steinhauer
IV NEW PERSPECTIVES IN HEMOFILTRATION AND PLASMAPHERESIS
Continuous arterio-venous hemofiltration:
Optimization of technical procedures
and new directions ............................... 167
C. Ronco
Is continuous haemofiltration superior to inter
mittent dialysis and haemofiltration
treatment? ....................................... 181
H.G. Sieberth, and H. Kierdorf
Therapeutic apheresis update ........................... 193
H.J. Gurland
Treatment combining plasmapheresis and pulse
cyclophosphamide in severe systemic
lupus erythematosus .............................. 203
J.O. Schroeder, and H.H. Euler
Index .................................................. 215
viii
PROTEIN CATABOLIC FACTORS IN PATIENTS ON RENAL
REPLACEMENT THERAPY
Jonas Bergstrom
Department of Renal Medicine, Huddinge University
Hospital, Karolinska Institute
S-114 86 Huddinge, Sweden
PROTEIN MALNUTRITION IN HAEMODIALYSIS PATIENTS
Several reports have documented that malnutrition is
frequently present in patients with maintenance haemodialy
sis therapyl-o. Signs of malnutrition in regular dialysis
patients are reduced muscle mass assessed by anthropometric
methods, low concentration of albumin, transferrin, and
other liver-derived proteins, low alkali-soluble protein in
muscle in relation to dry fat-free weight and DNA, abnormal
plasma amino acid and intracellular amino acid profiles,
similar to those found in untreated uremia, indicating that
dialysis does not reverse these abnormalities. It is
generally accepted that suboptimal nutritional status is
associated with increased morbidity and may contribute to
poor rehabilitation and quality of life. Cutaneous energy
and other immune alterations strikingly similar to those
observed in malnutrition have been documented in haemodia
lysis patients3 ,6,7 suggesting that protein-energy malnutri
tion may be a risk factor for infection and septicemia.
Malnutrition is an important factor for morbidity and
mortality in haemodialysis patients8 ,9.
PROTEIN AND ENERGY REQUIREMENTS IN HAEMODIALYSIS PATIENTS
Subjects with normal renal function have a minimum
daily protein requirement of about 0.5-0.6 g protein/kg/day.
Results of nitrogen belance studies in patients on main
tenance dialysis twice a week suggested that approximately
0.75 g/kg/day of high biological value protein is necessary
to maintain nitrogen equilibrium or a slightly positive
nitrogen balance.
According to more recent long-term studies this amount
of protein may not, however, be adequate. Signs of malnutri
tion have been observed in substantial fractions of ap
parently well-rehabilitated patients on maintenance haemo-
dialysis, who had a daily intake of about 1 g protein/kg
body weight/dayl .
HAEMODIALYSIS AS A CATABOLIC STIMULUS
There is evidence that the haemodialysis procedure per
se is a strong catabolic stimulus. Borah et al12 found that
during ingestion of a low protein diet (0.5 g/kg BW/day) ,
the nitrogen balance was markedly negative on dialysis days
and also slightly negative on nondialysis days. During
ingestion of a high protein diet (1.4 g/kg BW/day), the
nitrogen balance was still negative on dialysis days, but
positive on nondialysis days and the cumulative balance for
the study period was not different from O. It has been found
that the urea appearance rate was about 30 % higher during
dialysis than off dialysis which confirmed that the dialytic
procedure is a catabolic stimulus13 .
LOSS OF AMINO ACIDS
During haemodialysis average losses of free amino acids
in the dialysis fluid have been reported to be 5-8 g/dialy
sis14.1e, of which about one third are essential amino
acids. In addition, 4-5 g of peptide-bound amino acids are
lost per dialysis14 ; thus, the total losses of amino acids
are about 10-13 g/dialysis. Obviously, the losses of free
and bound amino acids during dialysis are insufficient to
completely account for the increased protein requirements
in haemodialysis patients compared to nondialyzed uremic
patients. Hence, one may conclude that additional factors
not related to the dialytic removal of amino acids (and
glucose) are involved.
BLOOD-MEMBRANE INTERACTION
It is now recognized that blood-membrane interaction in
a dialyzer induces several biological effects, such as
stimulation of the complement system, transient leukopenia,
aggregation of granulocytes, and release of granulocyte
enzymes, clotting, and thrombocyte activation16 . These signs
of bioincompatibility are especially prominent when using
dialyzers with regenerated cellulose (cuprophane) membranes.
It has been demonstrated that the blood-membrane interaction
induces release of elastase (measured as elastase-a1-
proteinase inhibitor complex) and other granulocytic enzymes
and it has been speculated on whether such enzymes might
have a role in the enhanced catabolism induced by acute
uremia and haemodialysis17 . However, since catabolic
granulocyte enzymes, e.g. elastase, are rapidly inactivated
in plasma, it is doubtful whether they could have a genera
lized effect on protein turnover.
More probably, blood-membrane interaction may cause the
release of other factors which directly or indirectly induce
catabolism of muscle protein.
The interleukin-1 (IL-1) hypothesis links several acute
and chronic symptoms in haemodialysis patients to monocyte
2
activation with synthesis and release of IL-1, a family of
polypeptides with molecular weights between 17 and 18,000
daltons with a broad range of biological properties as
sociated with both acute and chronic inflammatory
changes18 . Among the effects of IL-1 are fever, leucocyto
sis, acute phase protein synthesis by the liver, increased
muscle protein catabolism, myalgia, tissue inflammation,
stimulation of fibroblast activity, induction of collagenase
synthesis and bone resorption. IL-1 may act in conjunction
with tumor necrosis factor (TNF) or chachexin, another
monocyte product, synthetized and released as a consequence
of microbial stimulation and tissue injury.
The dialysis membrane may stimulate the generation of
IL-1 by a direct effect on adhering monocytes or indirectly
by complement activation with release of C5a, which is a
known IL-1 inducer. The dialysis fluid is not an innocent
bystander considering that acetate used as a buffer source
may contribute to IL-1 activation and that endotoxin
fragments which are strong activators of IL-1 synthesis and
release may pass through the dialysis membranes. We have
recently found that sham dialysis (i.e. blood circulation
through a dialyzer without circulating dialysate) using
cuprophane in non-uremic individuals induces significantly
increased muscle protein catabolism (Fig 1)19, whereas
blood-membrane contact with synthetic membranes (PAN,
polysulphone) had no such effect2o.21. The catabolic effect
of blood-cuprophane contact could be abolished by pre-treat
ment with indometacin19 i.e. was prostaglandin-mediated,
being consistent with a role of IL-1, which exerts its
protein-catabolic effect in muscle through mediation by
prostaglandin E2.
Based on the assumption that the enhanced catabolism
induced by blood-cuprophane interaction uniformly involved
the total muscle mass estimated to be 40 % of the body
weight, the increased release of tyrosine (an amino acid
which is not metabolized in muscle) corresponded to an
increased protein breakdown of about 20 g. In our experi
ments on normal man, endotoxin contamination from dialysis
fluid was not present and the blood exposure to the membrane
was small (blood flow 100 ml/min/m2 during 150 min) compared
with the exposure during clinical dialysis in most haemodia
lysis patients (higher blood flows, longer times, and
sometimes larger surface area). It is thus possible that
the stimulating effect on protein catabolism is much higher
during clinical dialysis than in our experiments.
ADAPTIVE DECREASE OF PROTEIN INTAKE
It may be difficult to fulfill the requirements of a
relatively high protein intake since some haemodialysis
patients seem to loose appetite and reduce their protein
intake spontaneously, especially if they are underdialyzed
with regard to small molecules. Experiences from the
National Cooperative Study on Dialysis Prescription9,
conducted in the USA, show that those patients who were
dialyzed according to a schedule which implied a low total
weekly clearance of urea had a significantly lower urea
3
