Kidney Biomarkers: Clinical Aspects and Laboratory Determination

Description

Since laboratory testing and biomarkers are an integral part in the diagnosis and treatment of kidney disease, Kidney Biomarkers: Clinical Aspects and Laboratory Determination covers currently used biomarkers as well as markers that are in development. Laboratories are increasingly more involved in the follow-up confirmatory laboratory testing and this unique volume showcases the collaboration needed to solve diagnostic clinical puzzles between the laboratory and clinician. This volume provides guidance on laboratory test selection and results interpretation in patients. Sources of inaccurate results in the measurement of kidney biomarkers are discussed along with possibility of eliminating such interferences. Each chapter is organized with a uniform easy-to-follow format with insightful case examples highlighting the collaboration between clinical laboratorians and clinicians. Cover Kidney Biomarkers: Clinical Aspects and Laboratory Determination Copyright Contributors Ideal biomarkers of acute kidney injury Introduction Serum creatinine Neutrophil gelatinase-associated lipocalin Cystatin C Kidney injury molecule-1 Interleuken-18 L type-fatty acid binding protein N-Acetyl-β-d-glucosaminidase TIMP-2 and IGFBP-7 Past, present, and future Prerenal vs ATI Cirrhosis Cardiorenal syndrome Kidney allocation from deceased donors The NephroCheck Acknowledgment Utility of the ``omics´´ in kidney disease: Methods of analysis, sampling considerations, and technical approa ... Introduction Statistical methods in analysis and interpretation of biomarkers in kidney disease Metrics for prediction performance (diagnostic potential) Quantification of prediction performance True positive rate and false positive rate Receiver-operating characteristic curve Summary indices Area under the ROC curve (AUC) Optimal prediction threshold Partial area under the curve Limitations of statistical metrics used for prediction performance Metrics to evaluating incremental diagnostic value Incremental value: How to evaluate? Improvement in discrimination Improvement in reclassification Net reclassification improvement Categorical net reclassification improvement Weighted net reclassification improvement Category-free net reclassification improvement Integrated discrimination improvement Decision and clinical use of analytic measures Recommendations for sample collection, storage, and preparation Tissue samples Biofluids Nontargeted versus targeted analysis Proteomics and metabolomics in nephrology Potential impact of proteomics and metabolomics in renal diseases Proteomics and the kidney The proteomics sample Urine Kidney tissue and cell culture Techniques used in proteome analysis Proteomics methods based on mass spectrometry First step: Protein separation Gel-based proteome analysis Gel-free proteome analysis Liquid chromatography (LC) Capillary electrophoresis Second step: Protein identification Two-dimensional gel electrophoresis coupled with mass spectrometry (2DE-MS) Liquid chromatography coupled to mass spectrometry (LC-MS/MS) Capillary electrophoresis coupled with mass spectrometry (CE-MS) Matrix-assisted laser desorption/ionization-time of flight coupled with mass spectrometry (MALDI-TOF/MS) Solid-phase chromatography coupled with mass spectrometry (SELDI-MS) Differential protein profiling Mass spectrometry (a) Peptide mass fingerprinting (b) Electrospray ionization (c) Peptide sequencing using tandem mass spectrometers Applications of mass spectrometry-based proteomics Proteomics methods based on ensembles or arrays of binding proteins Targeted proteomics approaches Proteomics raw data processing and feature identification Proteomics in renal research and nephrology Metabolomics and the kidney Metabolomic samples and preparation Samples Sample preparation Technology in metabolomics for data acquisition Nuclear magnetic resonance (NMR) spectroscopy Mass spectrometry Data analysis and interpretation Statistical multivariate analysis Metabolomics raw data processing and feature identification Metabolomics in renal research and nephrology Limitations of proteomics and metabolomic technologies Transcriptomics in kidney disease Transcriptomics and samples Transcriptomics and technology Transcriptomics in renal research and nephrology Extracellular vesicles and potential clinical use as biomarkers for renal disease Exosomes Exosomes as a source of protein biomarkers Exosomes as a source of RNA biomarkers Exosomes as potential therapeutic agents Epigenomics in kidney disease Genomic medicine in kidney disease When is recommended to do genetic testing? Type of genetic defects Copy number variation Single-gene mutation Diagnostic genomics technologies Chromosomal karyotyping Chromosomal microarray (CMA) Indications for the use of chromosomal microarrays Advantages of chromosomal microarrays Disadvantages of chromosomal microarrays Examples of chromosomal microarrays applications Multiplex ligation-dependent probe amplification Sanger (dideoxy) DNA sequencing Indications for the use of Sanger DNA sequencing Advantages of Sanger DNA sequencing Disadvantages of Sanger DNA sequencing Examples of Sanger DNA sequencing applications Next-generation sequencing (NGS) Targeted NGS panels Indications for the use of targeted NGS panel Advantages of targeted NGS panel Disadvantages of targeted NGS panel Examples of targeted NGS panel applications Whole-exome sequencing (WES) Indications for the use of whole-exome sequencing Advantages of whole-exome sequencing Disadvantages of whole-exome sequencing Example of whole-exome sequencing applications Whole-genome sequencing (WGS) Indications for the use of whole-genome sequencing Advantages of whole-genome sequencing Disadvantages of whole-genome sequencing Examples of whole-genome sequencing applications Genetic linkage mapping and association approaches Linkage analysis (rare disease: Mendelian inheritance) Homozygosity mapping Genome-wide association studies (GWAS; common diseases: complex inheritance) Clinical implications of genetic diagnosis Utility in patient care Confirmation of diagnosis Newborn and prenatal screening Better understanding of pathophysiology Supporting clinical management Interpretation challenges and reporting Return of results Continuous review Genetic education and counseling Ethical, legal, and social implications (ELSIs) of genomic research Participation in genetic research Minority populations Pediatric genetic testing Legal protection Data storage Costs and settings References Further reading Biomarkers in acute kidney disease Introduction Definition of AKI RIFLE classification AKIN classification KDIGO classification Limitations of acute kidney injury markers The quest for the ideal acute kidney injury biomarkers Neutrophil gelatinase-associated lipocalin Cystatin C Interleukin 18 Kidney injury molecule 1 (KIM-1) Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 Conclusions References Biomarkers in diabetic kidney disease Diabetic kidney disease Urine albumin Urine protein Plasma creatinine Cystatin C Neutrophil gelatinase-associated lipocalin (NGAL) Clusterin Transforming growth factor-β1 and bone morphogenetic protein-7 Urine immunoglobulin G, ceruloplasmin, and transferrin Immunoglobulin G4 and Smad1 Adiponectin Fibroblast growth factor 23 Retinol-binding protein Vascular endothelial growth factor Nephrin Glycosaminoglycans Tumor necrosis factor-α Podocalyxin Wilm's tumor-1 Microribonucleic acids Conclusions References Further reading Biomarkers in renal vasculitis Introduction ANCA-associated vasculitis What are ANCAs? How do ANCAs cause vasculitis? ANCA as a biomarker for diagnosis ANCA as a biomarker for disease activity ANCA as a biomarker for treatment response Other biomarkers in AAV Inflammatory biomarkers Other neutrophil activation biomarkers Other antibodies Leukocyte activation biomarkers Complement Endothelial injury and repair biomarkers Biomarker panel Urinary biomarkers Anti-GBM disease IgA vasculitis/Henoch-Schönlein purpura Cryoglobinemic vasculitis Anti-C1q vasculitis References Biomarkers in renal cancer Introduction Imaging biomarkers in renal cancer Positron emission tomography Magnetic resonance imaging Urine biomarkers in renal cancer Serum biomarkers in renal cancer Summary References Biomarkers in essential hypertension Introduction Biomarkers of pathophysiology Pathophysiologic mechanisms Biomarkers for genetic susceptibility Biomarkers for kidney, RAAS, and SNS dysfunction Glomerular filtration rate, serum creatinine, cystatin-C Urinary albumin creatinine ratio Interstitial tissue sodium content Other biomarkers Biomarkers for vascular dysfunction and damage Biomarkers of endothelial dysfunction Brachial artery flow-mediated dilatation Peripheral artery tonometry Serum vitamin D Markers of vascular damage and remodeling Endothelial microparticles Pulse wave velocity Biomarkers of inflammation and oxidative stress C-reactive protein Serum uric acid Homocysteine Multibiomarker approach Novel biomarkers of oxidative stress Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 Oxidized LDL 8-Isoprostaglandin F2a Neutrophil-to-lymphocyte ratio Red cell distribution width Biomarkers predictive of development of hypertension Peripheral blood pressure Markers of renal function Biochemical markers Biomarkers predicting treatment response and monitoring therapy Blood pressure and its several dimensions Blood pressure variability Central blood pressure Pulse pressure Biomarkers in disease progression and target organ damage Renal damage Cardiac damage Cerebral damage Retinal damage Biomarkers to individualize antihypertensive treatment Conclusion References Renal biomarkers of preeclampsia Introduction Early and late preeclampsia Other hypertensive disorders of pregnancy Chronic hypertension Gestational hypertension Superimposed preeclampsia Incidence of preeclampsia Global burden Predisposing factors Pathogenesis Clinical features Effect on kidney Effect on cardiovascular system Liver and coagulation abnormalities Effects on nervous system Fetal complications Biomarkers Angiogenic proteins Angiogenic proteins as potential biomarkers First-trimester screening sFlt-1 and sFlt-1/PlGF ratio Soluble endoglin PP-13 and PAPP-A Matrix metalloproteinases Galectin-7 Copeptin Podocyte glycoproteins and extracellular vesicles Cystatin C Serum uric acid Urinary kallikreins Cell-free DNA Clinical utility of biomarkers in disease management References Further reading Index Back Cover