Urinary Enzymes

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.