Prescribing Hemodialysis: A Guide to Urea Modeling

308 Pages·1990·16.897 MB·English

by  Thomas A. Depner M.D. (auth.)

PRESCRIBING HEMODIALYSIS
A Guide to Urea Modeling
DEVELOPMENTS IN NEPHROLOGY
Cheigh, J.S., Stenzel, K.H. and Rubin, A.L. (eds.): Manual of Clinical
Nephrology of the Rogosin Kidney Center. 1981. ISBN 90-247-2397-3.
Nolph, K.D. (ed.): Peritoneal Dialysis. 1981 ed.: out of print. 3rd revised and
enlarged ed. 1988 (not in this series). ISBN 0-89838-406-0.
Gruskin, A.B. and Norman, M.E. (eds.): Pediatric Nephrology, 1981.
ISBN 90-247-2514-3.
Schuck, 0.: Examination of the Kidney Function. 1981. ISBN 0-89838-565-2.
Strauss, J. (ed.): Hypertension, Fluid-electrolytes and Tubulopathies in Pediatric
Nephrology. 1982. ISBN 90-247-2633-6.
Strauss, J. (ed.): Neonatal Kidney and Fluid-electrolytes. 1983.
ISBN 0-89838-575-X.
Strauss, J. (ed.): Acute Renal Disorders and Renal Emergencies. 1984.
ISBN 0-89838-663-2.
Didio, L.J.A. and Motta, P.M. (eds.): Basic, Clinical, and Surgical Nephrology.
1985. ISBN 0-89838-698-5.
Friedman, E.A. and Peterson, C.M. (eds.): Diabetic Nephropathy: Strategy for
Therapy. 1985. ISBN 0-89838-735-3.
Dzurik, R., Lichardus, B. and Ouder, W. (eds.): Kidney Metabolism and
Function. 1985. ISBN 0-89838-749-3.
Strauss, J. (ed.): Homeostasis, Nephrotoxicity, and Renal Anomalies in the
Newborn. 1986. ISBN 0-89838-766-3.
Oreopoulos, D.G. (ed.): Geriatric Nephrology. 1986. ISBN 0-89838-781-7.
Paganini, E.P. (ed.): Acute Continuous Renal Replacement Therapy. 1986.
ISBN 0-89838-793-0.
Cheigh, J.S., Stenzel, K.H. and Rubin, A.L. (eds.): Hypertension in Kidney
Disease. 1986. ISBN 0-89838~797-3.
Deane, N., Wineman, R.J. and Benis, G.A. (eds.): Guide to Reprocessing of
Hemodialyzers. 1986. ISBN 0~89838-798-1.
Ponticelli, C., Minetti, L. and D'Amico, G. (eds.): Antiglobulins, Cryoglobulins
and Glomerulonephritis. 1986. ISBN 0-89838-810-4.
Strauss, J. (ed.), with the assistance of L. Strauss: Persistent Renal-genitourinary
Disorders. 1987. ISBN 0-89838-845-7.
Andreucci, V.E. and Dal Canton, A. (eds.): Diuretics: Basic, Pharmacological,
and Clinical Aspects. 1987. ISBN 0-89838-885-6.
Bach, P .H. and Lock, E.H. (eds): Nephrotoxicity in the Experimental and
Clinical Situation, Part 1. 1987. ISBN 0-89838-977-1.
Bach, P.H. and Lock, E.H. (eds.): Nephrotoxicity in the Experimental and
Clinical Situation, Part 2. 1987. ISBN 0-89838-980-2.
Gore, S.M. and Bradley, B.A. (eds.): Renal Transplantation: Sense and
Sensitization. 1988. ISBN 0-89838-370-6.
Minetti, L., D'Amico, G. and Ponticelli, C. (eds.): The Kidney in Plasma Cell
Dyscrasias. 1988. ISBN 0-89838-385-4.
Lindblad, A.S., Novak, J.W. and Nolph, K.D. (eds.): Continuous Ambulatory
Peritoneal Dialysis in the USA. 1989. ISBN 0-7923-0179-X.
Andreucci, V.E. and Dal Canton, A. (eds.): Current Therapy in Nephrology.
1989. ISBN 0-7923-0206-0.
Depner, T.A. (ed.): Prescribing Hemodialysis: A Guide to Urea Modeling. 1990.
ISBN 0-7923-0833-6.
PRESCRIBING HEMODIALYSIS
A Guide to Urea Modeling
Thomas A. Depner, M.D.
University of California, Davis
~.
"
Kluwer Academic Publishers
BostonlDordrechtILondon
Distributors for North America:
Kluwer Academic Publishers
101 Philip Drive
Assinippi Park
Norwell, Massachusetts 02061 USA
Distributors for all other countries:
Kluwer Academic Publishers Group
Distribution Centre
Post Office Box 322
3300 AH Dordrecht, THE NETHERLANDS
Library of Congress Cataloging-in-Publication Data
Depner, Thomas A.
Prescribing hemodialysis : a guide to urea modeling I Thomas A.
Depner.
p. cm.
Includes bibliographical references.
ISBN-13: 978-1-4612-8811-4 e-ISBN-13: 978-1-4613-1509-4
DOl: 10.1007/978-1-4613-1509-4
1. Hemodialysis-Evaluation-Mathematical models. 2. Urea
-Pharmacokinetics-Mathematical models. I. Title.
[DNLM: 1. Blood Urea Nitrogen. 2. Hemodialysis. 3. Kidney
Failure, Chronic-therapy. 4. Models, Biological. 5. Urea
-metabolism. 6. Urea-pharmacokinetics. WJ 342 D421p]
RC901.7.H45D47 1990
617.4'61059-dc20
DNLM/DLC
for Library of Congress 90-4842
CIP
Copyright © 1991 by Kluwer Academic Publishers
Softcover reprint of the hardcover 1st edition 1991
Seventh Printing 2002.
All rights reserved. No part of this publication may be reproduced, stored in a
retrievel system or transmitted in any form or by any means, mechanical, photo
copying, recording, or otherwise, without the prior written permission of the
publisher, Kluwer Academic Publishers, 101 Philip Drive,Assinippi Park, Norwell,
Massachusetts 02062.
Printed on acid-free paper.
This printing is a digital duplication of the original edition.
DEDICATION
To my patients, with sincere hope for a healthier future, and to my family,
Celeste, Charles, Kristine, and Ivy, for their love and understanding.
TABLE OF CONTENTS
Foreword by Raymond Hakim xi
Preface xiii
Listing of variables used throughout this book xix
Acknowledgements xxii
1. UREMIC TOXINS & DIALYSIS I
The uremic syndrome I
Role of protein nitrogen metabolism 2
Clinical measurement of uremia 3
Effect of dialysis on the uremic syndrome 6
Proposed uremic toxins 8
Alternatives to the single-toxin theory 8
Protein and tissue binding of proposed uremic toxins 13
Toxic contributions of dialysis itself 15
Where urea fits into the toxin theories 17
2. UREA METABOLISM: CLINICAL CHEMISTRY OF UREA 25
Excretion of nitrogenous waste products: comparative physiology 26
Biochemistry of urea 27
Inborn errors of urea metabolism: urea cycle enzymopathies 31
Urea transport 32
Nitrogen recycling 32
Methods of urea measurement 33
The toxicity of urea 34
3. UREA MODELING: INTRODUCTION 39
Definition of modeling 39
Evolution of urea modeling 41
Why urea instead of other solutes? 42
Quantifying hemodialysis therapy 43
-Quality assurance programs and urea modeling 47
Urea modeling development and techniques 48
What is the purpose of urea modeling? 50
Urea modeling for high-flux, short-duration dialysis 52
What clinical data are provided by urea modeling? 53
Significance of the urea distribution volume (V) 53
Significance of the urea nitrogen generation rate (G) 55
Components of the dialysis prescription 58
Measures of prescription effectiveness 59
vii
4. SINGLE-COMPARTMENT MODEL 65
Models for hemodialysis urea kinetics 65
Overview of kinetic analysis 67
Laws of diffusion 69
First-order kinetics: clearance, rate constant, half-life, and
exponential decline 70
The single-compartment model 72
Constant-volume model, ~hree BUN measurements 74
Evaluation of the constant-volume model 77
Variable-volume model, three BUN measurements 78
Source code for the variable-volume model, three BUN values 79
Two-BUN method, variable volume 81
Comparison of the two-BUN method with the three-BUN method 85
Source code for the variable-volume model, two BUN values 88
5. MULTICOMPARTMENT MODELS 91
Urea compartments in normal humans 91
Limitations of the single-compartment model 92
Description of the two-compartment model 93
Site of urea generation 95
Postdialysis rebound in urea concentration 96
Two-compartment modeling techniques 97
Solutions to equations for the two-compartment model 98
Graphic description of the two-compartment model 101
High-flux dialysis and two compartments 102
Solutes with low mass transfer coefficients 103
Measuring the intercompartment mass transfer area coefficient 104
A comparison of one-compartment with two-compartment models 106
The direct quantification method 106
Impact of pool number on calculated variables 107
Determinants of postdialysis urea rebound 110
Two-compartment model with variable ECF volume 112
Two-compartment model with variable ECF and ICF volume 116
The magnitude of intracellular swelling 117
Additional compartments 119
Recommendations regarding modeling with one versus
two compartments 120
Blood sampling techniques and precautions 122
6. A PRACTICAL SOLUTION: UREAKIN 127
Value of the computer program 129
Description of the program 130
viii
Theoretical basis for the program 130
Conventions and assumptions 130
Files and file extensions used by UREAKIN 131
Options available from the main menu 133
Refinements to UREAKIN 164
7. REFINEMENTS AND APPLICATION OF UREA MODELING 167
Measuring blood urea concentrations 167
Compensation for blood and plasma water content 169
Dialyzer urea clearance 174
Effect of fluid balance on kinetic measurements 178
Recirculation of dialyzer venous blood 183
Residual (native kidney) urea clearance: its significance 187
Simplified methods for urea modeling 190
8. MEASURING DIALYSIS: HOW MUCH IS ENOUGH? 195
Historical methods 196
KtIV: A yardstick for dialysis therapy 196
Measuring dialysis outcome 197
The adequacy of dialysis 202
Comparing dialysis outcome with the prescription 222
9. EXAMPLES OF UREA MODELING 225
Case 1: Expected results in an average adult patient 226
Case 2: A case with no residual function and no weight gain
between dialyses; the effect of changing Kd• 227
Case 3: The patient with significant residual renal function (K) 228
Case 4: Effects of habitually large weight gains between dialyses 230
Case 5: The patient with high protein intake 232
Case 6: The patient with low protein intake 234
Case 7: The patient treated with high-flux dialysis 234
Case 8: The patient whose dialyzer clearance (Kd) varies from the expected
clearance 237
Case 9: Small patients and the pediatric patient 240
10. THE FUTURE 243
Dialysis versus other treatments for end-stage renal failure 243
Outcome parameters for high-flux dialysis 244
More complex models 244
Modeling other solutes 245
Better markers for uremia 246
ix
Improved blood flow monitoring 247
Dialysate modeling 248
Real-time monitoring of urea kinetics 248
Urea modeling from the total-care perspective 250
APPENDICIES 253
Appendix A. Source code for a single-compartment,
variable-volume model: three-BUN method 254
AppendixB. Source code for a single-compartment,
variable-volume model: two-BUN method 255
Appendix C. Source code for a two-compartment,
fixed-volume model 258
AppendixD. Numerical solution for a two-compartment,
variable-ECV model 259
AppendixE. Description of a two-compartment, osmotic
model with variable ECV and ICV 261
Appendix F. Interpreting the results of urea modeling 263
AppendixG. Useful equations 265
AppendixH. Examples of data collection forms 269
Appendix I. Examples of modeling reports 273
Index 281
x
FOREWORD
What regulation shall we have for the operation? Shall a man transfuse
he knows not what. to correct he knows not what. God knows how (l)?
Dr. Henry Stubbs
Royal College of Physicians
circa 1670
If dialysis therapy were a new phannaceutical product being evaluated by the
FDA now, it might not be approved for marketing. The recommended dose, its
potential toxicity, the side effects of under-or over-dialysis as well as its efficacy
have been the subject of very few studies. The high mortality rate associated with
the treatment may raise a few eyebrows.
That it is a life-saving modality of treatment is undoubtedly true for more than
100,000 patients in the United States and for more than a million patients world
wide. Because dialysis has extended the lives of many people by a variable period
of time, most nephrologists have "rested on their laurels" and did not vigorously
pursue studies to optimize these treatments. But facts have a way of intruding in
all our lives and the facts are that the overall mortality rate of dialysis patients in the
United States is rising and stands close to 25% per year and is closer to 33% per year
for patients between the ages of 65 and 74 (2). These mortality figures are
considerably higher for age-adjusted dialysis populations in Europe and particu
larly in Japan, and certainly for the age-adjusted nonnal population.
The reasons for this trend of increasing mortality can and have been debated in
several forums particularly in the recent past (3); however, there is increasing
evidence that overlaying the multitude of factors that impact on morbidity and
mortality of this patient population (4,5) is the prescription of inadequate amounts
of dialysis (6,7). It is perhaps no coincidence that the mortality rate is rising at a
time when the average dialysis time is decreasing, and as government reimburse
ments for dialysis procedures have declined (4).
Why a book on prescribing hemodialysis? One can argue that a book dedicated
to the potentially single most important issue in the lives of a million people is
justification enough. But there are more positive reasons for this book. Dialysis
prescription is no longer an art, but a science founded on good theoretical principles
that should be relatively simple to apply. A book that explains the fundamentals and
shows the "how to" of applying these principles to a rational prescription is sorely
needed. Another good reason for such a book is that it allows us to have the courage
of our convictions when we are negotiating with patients about their time on
dialysis. It is only by understanding the rationale of prescribing 4 or more hours
instead of 3 hours of dialysis each time that we can convince our patients of the
importance and necessity of this additional burden. It is by understanding the
xi