Urinary Enzymes: In Clinical and Experimental Medicine

ISBN-13: 9783642843150 / Angielski / Miękka / 2011 / 326 str.

Klaus Jung; Hermann Mattenheimer; Ulf Burchardt

Opis

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."

Spis treści

1 Biochemical, Pathobiochemical, and Morphological Fundamentals of the Excretion of Urinary Enzymes.- 1 Origin of Enzymes in Urine.- 1.1 Blood Plasma.- 1.2 Blood Cells.- 1.3 Microorganisms.- 1.4 Urinary Tract and Sperm.- 1.5 Kidney.- 2 Distribution of Diagnostically Relevant Enzymes Along the Nephron.- 2.1 Introduction.- 2.2 Heterogeneity of the Mammalian Kidney.- 2.3 Methods to Quantitate Enzymes Along the Nephron.- 2.4 Localization of Diagnostically Relevant Enzymes Along the Nephron.- 2.5 Changes in Enzyme Distribution Pattern in Diseased States.- 3 Mechanisms of Enzyme Release and Causes of Altered Enzyme Excretion.- 3.1 Altered Composition of Primary Urine.- 3.1.1 Low Molecular Mass Proteins (Especially Enzymes).- 3.1.2 High Molecular Mass Proteins.- 3.1.3 Lysosomotropic Agents.- 3.1.4 Detergentlike Substances.- 3.2 Influences and Mechanisms Altering Tubular Cells.- 3.2.1 Modification of Energy Supply.- 3.2.2 Modification of Membrane and Intraluminal Proteolytic Potential.- 3.2.3 Enzyme Induction.- 3.2.4 Impairment of the Cytoskeleton.- 3.2.5 Lipid Peroxidation.- 3.2.6 Calcium Imbalance.- 3.2.7 Renal Tissue Enzyme Activity, Cellular Repair, and Enzymuria.- 4 Enzymuria as an Indicator of Renal Pathomorphology.- 4.1 Introduction.- 4.2 Principles of Renal Pathophysiology and Morphology.- 4.2.1 Glomerular Diseases.- 4.2.2 Tubular Diseases.- 4.3 Enzymuria.- 4.3.1 Brush Border Enzymes.- 4.3.2 Lysosomal Enzymes.- 4.3.3 Cytosolic Enzymes.- 4.4 Experimental Studies.- 4.5 Conclusions.- 5 Physiological Factors Influencing Enzyme Excretion.- 5.1 Urinary Flow.- 5.2 Circadian and Infradian Rhythms.- 5.3 Age and Sex.- 5.4 Genetic Component.- 5.5 Hormonal Influences and Nutrition.- 5.6 Pregnancy.- 5.7 Physical Activity.- 5.8 Environmental and Occupational Influences.- 2 Methodological Fundamentals of the Activity Determination of Urinary Enzymes.- 6 Preanalytical Treatment of Urine.- 6.1 Interference Factors.- 6.1.1 Hydrogen Ion Concentration.- 6.1.2 Enzyme Inhibitors.- 6.2 Collection and Storage of Samples.- 6.3 Preparation of Samples.- 6.3.1 Recommended Procedure.- 7 Quality Assurance.- 8 Methods for Measuring Urinary Enzyme Activities.- 8.1 Membrane-Bound Enzymes.- 8.1.1 Alanine Aminopeptidase.- 8.1.2 Alkaline Phosphatase.- 8.1.3 Gamma-glutamyltransferase.- 8.1.4 Aminopeptidase A (Angiotensinase A).- 8.2 Lysosomal Enzymes.- 8.2.1 N-Acetyl-?-D-glucosaminidase.- 8.3 Cytosolic Enzymes: Lactate Dehydrogenase.- 8.4 Kallikrein.- 8.5 Low-Molecular Mass Proteins with Enzymatic Properties.- 8.5.1 Lysozyme.- 8.5.2 Ribonuclease.- 8.6 Other Enzymes.- 8.6.1 Adenylate Kinase.- 8.6.2 Alanine Aminotransferase.- 8.6.3 Angiotensin I Converting Enzyme.- 8.6.4 Aspartate Aminotransferase.- 8.6.5 Arylsulfatase A.- 8.6.6 Dipeptidyl Aminopeptidase IV.- 8.6.7 ?-Galactosidase.- 8.6.8 ?-Glucosidase.- 8.6.9 ?-Glucuronidase.- 8.6.10 Glutamate Dehydrogenase.- 8.6.11 Glutathione Transferase.- 8.6.12 Malate Dehydrogenase.- 8.6.13 Trehalase.- 9 Basis of Reference.- 10 Reference Intervals.- 3 Urinary Enzymes in Clinical Medicine.- 11 Clinical Interpretation of Urinary Enzyme Excretion.- 12 Urinary Enzymes in Renal, Renal-Associated and Urological Disorders.- 12.1 Introduction.- 12.2 Enzymuria in Acute Renal Failure (together with U. Burchardt).- 12.3 Enzymuria in Acute Glomerulonephritis, Acute Pyelonephritis and Urinary Tract Infections.- 12.4 Enzymuria in Chronic Glomerulonephritis, Interstitial Nephritis and Chronic Renal Insufficiency (together with J. E. Scherberich).- 12.4.1 Enzymuria as Early Marker of Chronic Renal Diseases and Its Relation to Traditional Nephrological Parameters.- 12.4.2 Enzyme Pattern as a Tool for the Differential Diagnosis of Chronic Renal Diseases.- 12.5 Enzymuria in Renal and Urinary Tract Tumours.- 12.6 Enzymuria in Nephrolithiasis and After Extracorporeal Shock-Wave Lithotripsy.- 12.7 Enzymuria in Pregnancy-Associated Nephropathy.- 12.8 Enzymuria in Renal and Renovascular Hypertension, Renal Artery Stenosis and Essential Hypertension.- 12.9 Enzymuria in Systemic Diseases with Secondary Renal Involvement and in Inborn Errors of Metabolism.- 13 Urinary Enzymes in Kidney Transplantation.- 13.1 Introduction.- 13.2 Enzymuria in Uncomplicated Transplantation.- 13.3 Enzymuria in Acute Tubular Necrosis and Functionless Graft.- 13.4 Enzymuria in Rejection Episodes.- 13.5 Diagnostic Significance of Urinary Enzymes in Renal Transplantation.- 13.6 Conclusions and Future Aspects.- 14 Urinary Enzymes and Nephrotoxicity in Humans.- 14.1 Introduction.- 14.2 Enzymes Useful for Screening Nephrotoxicity.- 14.3 Relationship of Urinary Enzymes to Other Commonly Measured Parameters of Damage/Dysfunction.- 14.4 Examples of the Use of Enzyme Excretion to Monitor Drug-Induced Alterations in Patients.- 14.5 Coordination of Excretion.- 14.6 Monitoring Patients and Adjusting Regimes, Volunteer Studies and Screening Populations at Risk.- 14.7 Chronic Versus Acute.- 14.8 Heavy Metal Exposure.- 14.9 Practical Application of Urinary Enzyme Assays.- 14.10 Conclusions.- 15 Extrarenal Diseases.- 15.1 Heart Diseases.- 15.2 Hypertensive Vascular Disease.- 15.3 Disorders of the Hepatobiliary System.- 15.4 Diseases of the Pancreas.- 15.5 Malignant Diseases.- 15.6 Endocrine Disorders.- 15.6.1 Hyperthyroidism.- 15.6.2 Diabetes Mellitus.- 15.7 Disorders of the Connective Tissue.- 15.7.1 Rheumatoid Arthritis.- 15.7.2 Rheumatic Fever.- 15.7.3 Systemic Lupus Erythematosus.- 15.8 Surgery and Injuries.- 15.9 Inborn Errors of Metabolism.- 4 Urinary Enzymes in Animal Experiments.- 16 Animal Models.- 16.1 Introduction.- 16.2 Factors Affecting Enzymuria.- 16.2.1 Animal Handling and Environment.- 16.2.2 Age and Sex.- 16.2.3 Circadian Rhythms.- 16.3 Pre-analytical Guidelines.- 16.4 Conclusions and Outlook.- 17 Reference Values.- 18 Influence of Different Substances on Urinary Enzyme Excretion.- 18.1 X-Ray Contrast Media.- 18.1.1 Introduction.- 18.1.2 Enzymuria in Rats Following Contrast Media Administration.- 18.1.3 Enzymuria in Rabbits Following Contrast Media Administration.- 18.1.4 Enzymuria in Dogs Following Contrast Media Administration.- 18.1.5 Discussion.- 18.2 Aminoglycosides and Cephalosporines.- 18.2.1 Aminoglycosides.- 18.2.2 Cephalosporines.- 18.3 Diuretics.- 18.4 Heavy Metals.- 18.4.1 Cadmium.- 18.4.2 Hexavalent Chromium.- 18.4.3 Inorganic Lead.- 18.4.4 Mercury.- 18.4.5 Conclusions.- 18.5 Model Substances.- 18.5.1 Bovine Serum Albumin.- 18.5.2 Puromycin Aminonucleoside.- 18.5.3 Anthracyclines.- 18.5.4 Sodium Maleate.- 18.5.5 Halogenated Alkenes.- 18.5.6 Folic Acid.- 18.5.7 Ethlyeneimine, Propyleneimine.- 18.5.8 2-Bromoethanamine.- 18.5.9 Conclusions.- 5 Nephrotoxicity.- 19 Renal Enzymes as the Basis for Alternative Methods of Safety Screening In Vitro and Understanding the Mechanism of Nephrotoxicity.- 19.1 Introduction.- 19.2 In Vitro Methods for the Assessment of Nephrotoxity.- 19.2.1 Isolated Perfused Kidney.- 19.2.2 Renal Slices.- 19.2.3 Isolated Nephron Segments.- 19.2.4 Isolated Renal Cells and Cell Culture.- 19.2.5 Subcellular Fragments and Purified Enzymes.- 19.3 New Developments: The Use of Fluorescent Probes.- 19.4 Rational Basis for the Selection of In Vitro Tests for Toxicity Studies.- 19.5 Problem Areas and Potential Solutions.- 19.6 Conclusions.