Urinary Enzymes: in Clinical and Experimental Medicine

328 Pages·1992·11.056 MB·English

by  H. Mattenheimer, U. Burchardt (auth.), Docent Dr. sc. med Klaus Jung, Prof. (emer.) Hermann Mattenheimer M.D., D.Sc, Prof. Dr. sc. med Ulf Burchardt (eds.)

K. lung H. Mattenheimer
U. Burchardt
(Eds.)
Urinary
Enzytnes
in Clinical and
Experimental Medicine
With 71 Figures and 41 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona Budapest
Docent Dr, sc< med. Klaus Jung
Department of Experimental Organ Transplantation
University Hospital Charite
Humboldt University Berlin
Landsberger Allee 49, 0-1017 Berlin, FRG
Prof. (emer.) Hermann Mattenheimer M.D., D.Sc.
Department of Biochemistry
Rush-Presbyterian-St. Luke's Medical Center
1653 W. Congress Parkway, Chicago, Ill. 60612, USA
Prof. Dr. sc. med. Ulf Burchardt
Department of Medicine
District Hospital Frankfurt
Miillroser Chaussee 7, 0-1200 Frankfurt (Oder), FRG
ISBN-13: 978-3-642-84315-0 e-ISBN-13: 978-3-642-84313-6
001: 10.1007/978-3-642-84313-6
Library of Congress Cataloging-in-Publication Data
Urinary enzymes in clinical and experimental medicine/K. lung, H. Mattenheimer, U. Burchardt, (eds.).
Includes index.
ISBN 978-3-642-84315-0
1. Clinical enzymology. 2. Urine-Analysis. I. lung, K. II. Mattenheimer, Hermann. III. Burchardt, U.
[DNLM: 1. Urologic Diseases-diagnosis. 2. Urologic Diseases--enzymology. 3. Urologic Diseases-
pathophysiology. QY 185 U765] RB48.U75 1992 616.6'07566-<1c20 DNLM(DLC for Library of Congress
91-5221
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Preface
Interest and research in urinary enzymology were incited about three decades
ago by reports that urinary enzymes are elevated in diseases of the kidney and
urinary tract. Of the more than 40 hydrolases, oxidoreductases, transferases, and
lyases identified in human and animal urine, only ten or so are being used as
diagnostic indicators. Recognition of the quantitative distribution of enzymes in
the various anatomical and functional parts of the nephron and advances in our
understanding of the handling of proteins by the kidney have made it possible to
associate urinary enzyme activity patterns with physiological and pathophysio
logical functions of the nephron.
Confidence in the diagnostic value of urinary enzymes is not unanimous
among clinicians and among scientists. The main reason for the difference in
opinion may well be that the variability in data exceeds the variability one is
accustomed to in the diagnostic enzymology of blood plasma enzymes.
In contrast to plasma enzymes, which are protected by an "enzyme friendly"
milieu, enzymes released into the urine encounter an "enzyme hostile" environ
ment: no or little protective protein, variable pH, variable volume, variable
metabolite and salt concentrations, variable concentrations of enzyme in
hibitors. Through advances in methodology some of these factors can now be
controlled; standardization of urine collection periods and preanalytical treat
ment are as important as optimization of assay methods.
This book is the first comprehensive text on urinary enzymology and gives
an up-to-date account of the accomplishments in this field. The recognition that
urinary enzymes are valuable markers for the nephrotoxic side effects of drugs
has broadened the application of urine analysis. The contributing authors are all
actively engaged in basic and/or clinical research in nephrology and renal and
urinary enzymology; nonetheless, different authors do not attribute the same
diagnostic value to enzyme measurements in urine.
We wish to acknowledge the helpful cooperation of Dr. Wieczorek and
his editorial staff of the Springer-Verlag.
Berlin (FRG) K. Jung
Chicago (USA) H. Mattenheimer
Frankfurt/Oder (FRG) U. Burchardt
in May 1991
List of Contributors
Bach, Peter H.
Polytechnic of East London, School of Science, Romford Road, London
E15 4LZ, United Kingdom
Bertsch, Thomas
ForsthausstraBe 2, W-6830 Schwetzingen, FRG
Bhargava, Akhil S.
Schering AG, Department of Experimental Toxicology Research Laboratories,
Miillerstr. 170/178, W-1000 Berlin 65, FRG
Bleuel, Helga
Boehringer Mannheim GmbH, Sandhofer Str. 116, W-6800 Mannheim 31, FRG
Bode, Gerd
Boehringer Mannheim GmbH, Sandhofer Str. 116, W -6800 Mannheim 31, FRG
Bomhard, Ernst Michael
Bayer AG, Institute of Industrial Toxicology, Friedrich-Ebert-Str. 217-333,
W-5600 Wuppertal 1, FRG
Burchardt, Ulf
Department of Internal Medicine, District Hospital Frankfurt/Oder,
Miillroser Chaussee 7, 0-1200 Frankfurt/Oder, FRG
Fuchs, Eberhard
German Primate Center, Kellnerweg 4, W-3400 Gottingen, FRG
Grotsch, Horst
Hoechst AG, Pharma Research, Postfach 800320,
W-6230 Frankfurt am Main 80, FRG
Guder, Walter G.
Institute for Clinical Chemistry, Bogenhausen Community Hospital,
Englschalkinger Str. 77, W-8000 Munich 81, FRG
viii List of Contributors
Giinzel, P~ter
Schering AG, Department of Experimental Toxicology, Research Laboratories,
Miillerstr. 170/17S, W-I000 Berlin 65, FRG
Hofmeister, Rainer
Schering AG, Department of Experimental Toxicology, Research Laboratories,
Miillerstr. 170/17S, W-I000 Berlin 65, FRG
Hropot, Max
Hoechst AG, Pharma Research, Postfach SO 03 20,
W-6230 Frankfurt am Main SO, FRG
Jung, Klaus
Department of Experimental Organ Transplantation, University Hospital
Charite, Humboldt University Berlin, Landsberger Allee 49, 0-1017 Berlin,
FRG
Kotanko, Peter
Hospital Barmherzige Briider, Department of Internal Medicine,
Marschallgasse 12, A-S020 Graz, Austria
Maruhn, Dieter
Bayer AG, Pharma Research Center, Section Medicine and Development,
Aprather Weg, Postfach 10 1709, W-5600 Wuppertal 1, FRG
Mattenheimer, Hermann
32 Forestway Drive, Deerfield, Illinois 60015, USA
Price, Robert G.
Biochemistry Section, Division of Biomolecular Sciences, King's College
London, University of London, Campden Hill Road, London WS 7A H,
United Kingdom
Rebel, Wolfgang
Boehringer Mannheim GmbH, Sandhofer Str. 116,
W-6S00 Mannheim 31, FRG
Scherberich, Jiirgen E.
Department of Nephrology, Center of Internal Medicine, Johann
Wolfgang-Goethe-University, Theodor-Stern-Kai 7, W-6000 Frankfurt am
Main 70, FRG
Schmid, Heide
Institute of Pathology, University of Tiibingen, Liebermeisterstr. S,
W-7400 Tiibingen, FRG
List of Contributors ix
Simane, Zdenek J.
E. Merck
Clinical Research, Frankfurter Str. 250, W-6100 Darmstadt 1, FRG
Slabke, Peter
Schering AG, Department of Experimental Toxicology, Research Laboratories,
Miillerstr. 170/178, W-lOOO Berlin 65, FRG
Whiting, Paul H.
University of Aberdeen, Department of Clinical Biochemistry, Medical
Buildings, Foresterhill, Aberdeen AB9 2ZD, Scotland, United Kingdom
Wilks, Martin F.
Nephrotoxicity Research Group, The Robens Institute of Health and Safety,
University of Surrey, Guildford, Surrey GUZ 5XH, United Kingdom
Contents
Preface... . . . . ....... .. . ....... . .. ... ........ .. . . . . .. . . . .. v
List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. vii
List of Enzymes Appearing in the Text. . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
Part 1
Biochemical, p,athobiochemical, and Morphological Fundamentals
of the Excretion of Urinary Enzymes ........................... .
1 Origin of Enzymes in Urine
(H. Mattenheimer, U. Burchardt). . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1 Blood Plasma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Blood Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Microorganisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.4 Urinary Tract and Sperm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.5 Kidney. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2 Distribution of Diagnostically Relevant Enzymes Along the Nephron
(H. Schmid, W.G. Guder). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.1 Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2 Heterogeneity of the Mammalian Kidney . . . . . . . . . . . . . . . . . . 9
2.3 Methods to Quantitate Enzymes Along the Nephron. . . . . . . .. 12
2.4 Localization of Diagnostically Relevant Enzymes Along
the Nephron. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 14
2.5 Changes in Enzyme Distribution Pattern in Diseased States. . .. 16
3 Mechanisms of Enzyme Release and Causes of Altered Enzyme
Excretion
(u. Burchardt, J.E. Scherberich). . . . . . . . . . . . . . . . . . . . . . . . . . . .. 21
3.1 Altered Composition of Primary Urine. . . . . . . . . . . . . . . . . . .. 21
3.1.1 Low Molecular Mass Proteins (Especially Enzymes) . . . .. 21
3.1.2 High Molecular Mass Proteins. . . . . . . . . . . . . . . . . . . . .. 25
3.1.3 Lysosomotropic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . .. 26
3.1.4 Detergentlike Substances. . . . . . . . . . . . . . . . . . . . . . . . . .. 28
3.2 Influences and Mechanisms Altering Tubular Cells. . . . . . . . . .. 29
3.2.1 Modification of Energy Supply. . . . . . . . . . . . . . . . . . . . .. 29
xii Contents
3.2.2 Modification of Membrane and Intraluminal Proteolytic
Potential. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 30
3.2.3 Enzyme Induction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 30
3.2.4 Impairment of the Cytoskeleton. . . . . . . . . . . . . . . . . . . .. 31
3.2.5 Lipid Peroxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32
3.2.6 Calcium Imbalance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 36
3.2.7 Renal Tissue Enzyme Activity, Cellular Repair,
and Enzymuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
4 Enzymuria as an Indicator of Renal Pathomorphology
(W. Rebel, T. Bertsch, G. Bode, H. Bleuel). . . . . . . . . . . . . . . . . . . .. 43
4.1 Introduction......................................... 43
4.2 Principles of Renal Pathophysiology and Morphology. . . . . . .. 45
4.2.1 Glomerular Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 45
4.2.2 Tubular Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 45
4.3 Enzymuria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51
4.3:1 Brush Border Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . .. 53
4.3.2 Lysosomal Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 54
4.3.3 Cytosolic Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 56
4.4 Experimental Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 57
4.5 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 66
5 Physiological Factors Influencing Enzyme Excretion
(U. Burchardt, K. Jung) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73
5.1 Urinary Flow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73
5.2 Circadian and Infradian Rhythms. . . . . . . . . . . . . . . . . . . . . . .. 75
5.3 Age and Sex. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 77
5.4 Genetic Component. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 78
5.5 Hormonal Influences and Nutrition. . . . . . . . . . . . . . . . . . . . . .. 79
5.6 Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 80
5.7 Physical Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 81
5.8 Environmental and Occupational Influences. . . . . . . . . . . . . . .. 82
Part 2
Methodologi.cal Fundamentals of the Activity Determination of Urinary
Enzymes. . . .. . . . . . . .. . .. . . . . .. . . ... ... .. . . . ... . . .. . ... .. .. 87
6 Preanalytical Treatment of Urine
(H. Mattenheimer, D. Maruhn) . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89
6.1 Interference Factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89
6.1.1 Hydrogen Ion Concentration. . . . . . . . . . . . . . . . . . . . . .. 89
6.1.2 Enzyme Inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89
6.2 Collection and Storage of Samples. . . . . . . . . . . . . . . . . . . . . . .. 91
6.3 Preparation of Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 92
6.3.1 Recommended Procedure. . . . . . . . . . . . . . . . . . . . . . . . .. 93
Contents xiii
7 Quality Assurance
(Z.J. Simane). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 97
8 Methods for Measuring Urinary Enzyme Activities. . . . . . . . . . . . . .. 99
8.1 Membrane-Bound Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 99
8.1.1 Alanine Aminopeptidase (H. Mattenheimer, K. Jung,
H. Grotsch) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 99
8.1.2 Alkaline Phosphatase (K. Jung). . . . . . . . . . . . . . . . . . . . .. 105
8.1.3 Gamma-glutamyltransferase (Z.J. Simane) .............. 109
8.1.4 Aminopeptidase A (Angiotensinase A) (J.E. Scherberich) ... 116
8.2 Lysosomal Enzymes ................................... 118
8.2.1 N-Acetyl-fJ-D-glucosaminidase (Z.J. Simane) ............ 118
8.3 Cytosolic Enzymes: Lactate Dehydrogenase (A.S. Bhargava,
P. Slabke) ........................................... 125
8.4 Kallik~ein (K. Jung) ................................... 128
8.5 Low-Molecular Mass Proteins with Enzymatic Properties
(K. Jung) .............. : ............................ 133
8.5.1 Lysozyme (K. Jung) ............................... 133
8.5.2 Ribonuclease (K. Jung) ............................ 137
8.6 Other Enzymes (H. Mattenheimer, D. Maruhn) .............. 141
8.6.1 Adenylate Kinase ................................ 141
8.6.2 Alanine Aminotransferase .......................... 142
8.6.3 Angiotensin I Converting Enzyme .................... 142
8.6.4 Aspartate Aminotransferase ......................... 142
8.6.5 Arylsulfatase A .................................. 142
8.6.6 Dipeptidyl Aminopeptidase IV ...................... 142
8.6.7 fJ-Galactosidase .................................. 143
8.6.8 a-Glucosidase ................................... 143
8.6.9 fJ-Glucuronidase ................................. 143
8.6.10 Glutamate Dehydrogenase ........................ 143
8.6.11 Glutathione Transferase .......................... 143
8.6.12 Malate Dehydrogenase ........................... 144
8.6.13 Trehalase ...................................... 144
9 Basis of Reference
(K. Jung, D. Maruhn) ..................................... 147
10 Reference Intervals
(K. Jung). . . . . . . . . . . . . . . . . . . . . . . . . . .. . ................. 153
Part 3
Urinary Enzymes in Clinical Medicine ........................... 161