The importance of developing and defining biomarkers of kidney diseases that can be used for early diagnosis, assessment of severity, and long term prognosis has been emphasized by the American Society of Nephrology and the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK). Over the last ten years, there has been exponential growth in research on biomarkers of kidney diseases. Preclinical studies have been taken to the bedside and it is now possible to use biomarkers to diagnose certain kidney diseases at an earlier stage than has been possible with conventional tests. This prospect of early diagnosis and treatment of kidney diseases has made biomarker research one of the most exciting areas of kidney research.
The prevention or attenuation of the severity of disease necessitates early detection. In recent years this has been a focus relative to kidney disease. Biomarkers in Kidney Disease edited by Charles Edelstein summarizes advances in early detection and assessment of severity in an array of important kidney diseases. State of the art techniques, including metabolomics and proteomics, are discussed in areas of acute kidney injury, kidney transplantation, renal cancer, diabetic nephropathy and other glomerular diseases, as well as in preeclampsia.
Biomarkers in Kidney Disease is a seminal book, because nephrology has lagged behind other subspecialties in performing interventional trials which can improve the lives of their patients. A major reason is because the tools to detect kidney disease at the early stage have heretofore not been available. As in all diseases, prevention and attenuation of severity necessitates early intervention. The emergence of sensitive biomarkers of early kidney disease now has the potential to allow early detection and inter vention. With this book there is now a source which provides up to date and important information by distinguished authors about biomarkers available to detect early kidney disease.
Biomarkers of Kidney Disease offers a thorough examination of the latest findings in the field for both the practicing physician as well as the biomedical researcher. Coverage includes biomarkers of acute kidney injury, chronic kidney disease, kidney transplant rejection, delayed kidney allograft function, renal cell cancer, glomerular disease, diabetic nephropathy, and preeclampsia. This book is the most comprehensive reference yet published on the topic of biomarkers of kidney diseases.
Contents Chapter 1 - Characteristics of an Ideal Biomarker of Kidney Diseases
1. The Discovery of Biomarkers 1
2. Characteristics of an Ideal Biomarker 4
3. Biomarkers in Acute Kidney Injury 6
4. Biomarkers in Chronic Kidney Disease 11
5. The Example of NGAL as a Biomarker of Acute Kidney Injury 14
Chapter 2 - Statistical Considerations in Analysis and Interpretation of Biomarker Studies
1. Introduction 25
2. Planning a Study 27
2.1. Research objectives for assessing biomarker performance 27
2.2. Explore covariates that may affect biomarker values 27
2.3. Avoid overfitting 28
3. Statistical Methods to Quantify Classification Performance 28
3.1. True positive rate (TPR) and false positive rate (FPR) 28
3.1.1. Example e urine biomarker predicts AKI after cardiac surgery 29
3.2. ROC curve 30
3.3. Area under the curve (AUC) 32
3.4. Optimal classification threshold 32
3.5. Partial area under the curve 32
4. Sample Size Calculations 33
5. Emerging Methods 33
5.1. Standardized placement values 33
5.2. Risk models 34
5.2.1. Predictiveness curves 34
5.2.2. Net reclassification index (NRI) and integrated discrimination improvement (IDI) 36
6. Summary 36
Chapter 3 - The Role of Metabolomics in the Study of Kidney Diseases and in the Development of Diagnostic Tools
1. Introduction 40
1.1. Definitions 41
1.1.1. Why are metabolomics-based molecular markers expected to be more sensitive and specific than currently established markers used in nephrology? 41
1.1.2. Metabolomic-based molecular markers versus protein and genomic markers advantages and challenges 43
2. Metabolic Mapping of the Kidney 46
2.1. Cortex 46
2.2. Medulla 47
2.3. Papilla 47
3. Non-Targeted and Targeted Metabolomics 48
4. The Sample 54
4.1. Tissues 54
4.2. Biofluids 54
5. Analytical Technologies 56
5.1. NMR spectroscopy 56
5.2. Mass spectrometry 57
5.3. Other technologies for metabolic profiling 60
5.4. Chemometrics and databases 60
5.4.1. GC-MS 62
5.4.2. LC-MS 63
5.5. Normalization of urine data 63
5.6. Validation of analytical assays, quality control and standardization 64
6. Metabolic Molecular Marker Discovery and Development 65
7. Metabolomics in Renal Research and as Kidney Function, Disease and Injury Marker 68
7.1. Identification of disease, pharmacodynamic and toxicodynamic molecular mechanisms 69
7.2. Nephrotoxicity and drug development 71
7.3. Kidney transplantation 73
7.3.1. Organ quality, organ storage and ischemia reperfusion injury of kidney transplants 77
7.3.2. Immunosuppressant nephrotoxicity 77
7.3.3. Allo-immune reactions 80
7.4. Cancer 81
7.4.1. Urinary metabolite markers of renal cell carcinoma 82
7.4.2. Biochemical classification of renal carcinoma biopsy samples 82
7.4.3. Monitoring of cancer treatment effects 83
7.5. Urine as matrix for non-renal disease and injury 83
8. Metabolomics as Clinical Diagnostic Tool in Nephrology 85
8.1. Why hasn’t it worked? 85
8.2. How will it work?
Chapter 4 - The Role of Proteomics in the Study of Kidney Diseases and in the Development of Diagnostic Tools
1. Introduction 102
1.1. Why are molecular marker strategies considered predictive? 103
2. Non-targeted and Targeted Proteomics 106
2.1. Non-targeted 106
2.2. Targeted 109
3. Proteins and the Kidney 110
4. The Proteomics Sample 114
4.1. Kidney tissues and cell culture 115
5. Analytical Technologies 116
5.1. 2D gel proteomics 117
5.2. LC-MS 121
5.3. Labeling technologies for LC-MS analysis 124
5.4. Other mass spectrometry-based technologies 125
5.5. Non-targeted microarrays 126
5.6. Technologies for targeted proteomics 126
5.7. Database searches, biostatistics and annotation 130
5.7.1. Data processing 130
5.7.2. Peptide identification 130
5.7.3. Validation 131
5.7.4. Quantification 131
5.7.5. Annotation 132
5.8. Normalization of urine data 132
5.9. Validation of analytical assays, quality control and standardization 132
6. Proteomics in Renal Research and as a Marker for Kidney Function, Disease and Injury 135
6.1. Identification of disease, pharmacodynamic and toxicodynamic molecular mechanisms 135
6.2. Acute and chronic kidney injury
6.3. Nephrotoxicity and drug development 147
6.4. Kidney transplantation 148
6.5. Cancer 156
6.6. The effects of extra-renal proteome changes on the urine proteome 158
7. Proteomics as Clinical Diagnostic Tool in Nephrology 158
Chapter 5 - Biomarkers in Acute Kidney Injury
1. Serum Creatinine in Acute Kidney Injury 179
2. Interleukin-18 181
3. Neutrophil Gelatinase-associated Lipocalin 186
4. Kidney Injury Molecule-1 192
5. Tubular Enzymes 195
6. Cystatin C 197
7. Other Biomarkers of Acute Kidney Injury 201
7.1. IL-6 and IL-8 201
7.2. Liver fatty acid binding protein (L-FABP) 205
7.3. L1 cell adhesion molecule 206
7.4. Netrin 206
7.5. Exosomes 207
7.6. Urinary aprotinin 208
7.7. Nephronectin 209
7.8. Angiotensin converting enzyme insertion/deletion (I/D) genetic polymorphisms 209
8. Combinations of AKI Biomarkers 209
9. Summary 211
10. Biomarkers of Extra-renal Complications of Acute Kidney Injury 212
10.1. AKI and inflammation 213
10.1.1. Proinflammatory cytokines mediate organ dysfunction 213
10.1.2. Proinflammatory cytokines are increased in the serum in animal models of AKI 213
10.1.3. Clearance of proinflammatory cytokines may be impaired in acute kidney injury 214
10.1.4. Excess production and impaired clearance of proinflammatory cytokines may occur in AKI 214
10.1.5. Serum cytokines are increased in patients with AKI 215
10.1.6. Serum IL-6, IL-8 and IL-10 are increased in patients with established AKI and predict mortality 215
10.1.7. Serum IL-6 is an early biomarker of AKI 216
10.2. Pulmonary complications of AKI 217
10.2.1. Lung inflammation in experimental AKI 219
10.2.2. Potential role of IL-6 in AKI-mediated lung injury 220
10.2.3. Serum IL-6 and IL-8 increase 2 h after cardiopulmonary bypass-associated AKI and predict prolonged mechanical ventilation 221
Chapter 6 - Biomarkers in Kidney Transplantation
1. Biomarkers: An Overview 234
2. Biomarkers of Acute Kidney Injury Post-transplantation (Table 6.1) 234
2.1. Pre-transplant biomarkers 234
2.1.1. Tissue markers 234
2.1.2. Plasma markers 238
2.2. Post-transplant biomarkers 239
2.2.1. Tissue markers 239
2.2.2. Plasma markers 240
2.2.3. Urine markers 241
2.2.4. Genetic biomarkers of DGF 244
3. Biomarkers of Acute Rejection (Table 6.2) 245
3.1. Genetic biomarkers of acute rejection (Table 6.3) 245
3.2. Chemokines and acute rejection 254
3.3. Toll-like receptors (TLRs) and acute rejection 258
3.4. Gene transcripts and acute rejection 258
3.5. ELISPOT as a biomarker of acute rejection 264
3.6. Platelet activation and acute rejection 265
3.7. Serum markers of inflammation and acute rejection 265
3.8. Tissue biomarkers of acute rejection 267
3.9. B-cell activation and acute rejection (tissue biomarkers as predictors of response to therapy) 269
3.10. Cytokines as biomarkers of acute rejection 270
3.11. Urine flow cytometry and the diagnosis of acute rejection 271
3.12. Proteomic-based approaches to finding biomarkers of acute rejection 272
4. Biomarkers of Chronic Allograft Nephropathy (Table 6.4) 273
4.1. Tissue markers 273
4.2. Plasma markers 277
4.3. Genetic markers 278
4.4. Urine biomarkers 279
5. Biomarkers of Polyoma Virus Infection 279
6. Summary 283
Chapter 7 - Cystatin C as a Biomarker in Kidney Disease
1. Structure and Function of Cystatin C 291
2. Cystatin C Gene Structure and Cystatin C Production 292
3. Catabolism of Cystatin C 293
4. Cystatin C as a Marker for Glomerular Filtration Rate 294
5. Creatinine- and Cystatin C-based GFR-prediction Equations 298
6. The Lund Model: GFR-estimation with an Internal Quality Control 301
7. Abnormal Glomerular Filtration Quality: A New Marker for Kidney Disease. Use of Cystatin C to Identify It 302
8. Cystatin C and Aging Success 304
Chapter 8 - Biomarkers of Renal Cancer
1. Renal Cancer 313
1.1. Biology 314
1.2. Diagnosis and treatment 315
1.3. Staging and prognosis 316
2. Cancer Biomarkers e General Concepts 319
3. Renal Cancer Biomarkers 320
3.1. Diagnostic markers 321
3.1.1. Circulating markers 321
3.1.2. Histopathological diagnosis 323
3.2. Prognostic markers 324
3.2.1. Tissue-based markers 329
3.2.2. Circulating markers 334
3.2.3. Predictive markers 338
4. Conclusions 344
Chapter 9 - Urinary Proteomics and Candidate Biomarker Discovery for Diabetic Nephropathy
1. Introduction 352
2. Urinary Proteins as Candidate Biomarkers of Diabetic Nephropathy 354
3. Urinary Peptides as Candidate Biomarkers of Type 2 Diabetic Nephropathy and Chronic Kidney Disease 357
4. Urinary Peptides as Candidate Biomarkers of Early Progressive Renal Function Decline in Type 1 Diabetic Nephropathy 359
5. A Targeted Proteomic Analysis for Candidate Biomarkers of Early Renal Function Decline in Type 1 Diabetic Nephropathy 363
6. Future Developments and Applications of Proteomics for Biomarker Discovery 364
Chapter 10 - Biomarkers in Glomerular Disease
1. Biomarkers in Glomerular Diseases 368
1.1. Predictors of outcome in glomerular diseases 368
2. Biomarkers in Lupus Nephritis 368
2.1. Predictors of lupus nephritis class 369
2.2. Biomarkers that predict renal lupus flares 370
3. Membranous Nephropathy 372
4. Focal Segmental Glomerulosclerosis 374
5. Minimal Change Disease 375
6. IgA Nephropathy 376
7. ANCA-associated Vasculitis 378
8. Discovery of New Biomarkers using Proteomics 379
Chapter 11 - Biomarkers in Preeclampsia
1. Definition and Prevalence of the Disease 386
2. Pathophysiology and Mechanisms 387
3. Clinical Manifestations 389
3.1. The kidney 390
3.2. Liver and coagulation abnormalities 391
3.3. The brain 391
3.4. Fetal complications 392
3.5. Long term complications 392
4. Diagnosis 393
5. Biomarkers 395
5.1. Angiogenic markers 395
5.1.1. Sequential changes 397
5.1.2. High risk populations 402
5.1.3. Other antiangiogenic states 403
5.1.4. PlGF in the urine 404
5.1.5. Differential diagnosis 404
5.2. Placental protein-13 406
5.3. Pregnancy-associated plasma protein A 407
5.4. Renal dysfunction related tests 408
5.4.1. Serum uric acid 408
5.4.2. Proteinuria 408
5.4.3. Kallikreins 409
5.5. Free fetal nucleic acids 409
5.6. Uterine Doppler velocimetry 411
5.7. Combination of tests 412
6. Novel Biomarkers and Future Perspectives 414
6.1. Transcriptomics 414
6.2. Proteomics 416
6.3. Metabolomics 416
7. Conclusion 417
Index
Book Details
- Hardcover: 454 pages
- Publisher: Academic Press; 1 edition (September 27, 2010)
- Language: English
- ISBN-10: 0123756723
- ISBN-13: 978-0123756725
- Product Dimensions: 9.1 x 6 x 1.1 inches