Chronic Kidney Disease, Dialysis, and Transplantation: A Companion to Brenner and Rector’s The Kidney [4 ed.] 9780323529785, 0323529785

Table of contents :
Chronic Kidney Disease, Dialysis, and Transplantation: A Companion to Brenner and Rector’s The Kidney......Page 2
Copyright......Page 3
Section Editors......Page 4
List of Contributors......Page 5
Definition......Page 10
Staging......Page 11
Strengths and Limitations of the Current Chronic Kidney Disease Classification System......Page 13
Epidemiology of Chronic Kidney Disease......Page 14
Prevalence of Chronic Kidney Disease......Page 15
Prevalence and Incidence of Kidney Failure......Page 20
Prevalence of Treated Kidney Failure......Page 21
Chronic Kidney Disease (Not on Kidney Replacement Therapy) Costs......Page 22
Outcomes of Chronic Kidney Disease......Page 23
Outcomes Before Kidney Replacement Therapy......Page 25
Outcomes on Kidney Replacement Therapy......Page 28
Conclusion......Page 30
Determinants of Glomerular Filtration Rate......Page 34
Variability of Glomerular Filtration Rate......Page 35
Physiology of Urinary Clearance and the Measurement of GFR......Page 36
Clearance Methods......Page 37
Exogenous Filtration Markers......Page 38
Relationship of Glomerular Filtration Rate to Plasma Solute Concentrations......Page 40
Estimating Equations for Glomerular Filtration Rate......Page 41
Interpretation of Glomerular Filtration Rate Estimates......Page 42
3. Generation......Page 43
4. Renal Handling......Page 44
7. Creatinine as a Filtration Marker......Page 45
2. Plasma Levels......Page 47
7. Cystatin C as a Filtration Marker......Page 48
4. Renal Handling of Urea......Page 49
Novel Markers......Page 51
Diagnosis And Classification Of Diabetic Kidney Disease......Page 56
Hereditary Risk Factors......Page 57
Acute Kidney Injury......Page 58
Natural History......Page 59
Kidney Structural Changes In Diabetic Kidney Disease......Page 60
Pathophysiological Mechanisms In DKD......Page 61
Glycemic Control......Page 65
Antihypertensive Therapy......Page 67
Glucagon-like Peptide-1 Receptor Agonists......Page 69
Sodium–Glucose Cotransporter 2 Inhibitors......Page 71
Conclusions......Page 72
Pathophysiology of Renal Injury in Hypertensive Nephrosclerosis......Page 81
Target Level of BP Control......Page 83
Angiotensin Converting Enzime Inhibitors......Page 86
Angiotensin Receptor Blockers......Page 87
Aldosterone Antagonists......Page 88
Surgical Management......Page 89
Lifestyle Modification......Page 90
Conclusion......Page 91
Changes in the Glomerulus......Page 98
Electrolyte Management......Page 99
Identification of CKD in Older Adults......Page 100
Outcomes Associated With CKD in Older Adults......Page 102
Hypertension Management......Page 103
Proteinuria......Page 105
Multimorbidity And Complexity In Older Adults With Chronic Kidney Disease......Page 106
Dialysis Initiation in Older Adults......Page 107
Resources to Inform Productive Discussion......Page 108
Palliative Support as an Alternative or Adjunct to Dialysis Preparation......Page 111
Epidemiology of Pediatric CHRONIC KIDNEY DISEASE......Page 117
Defining Chronic Kidney Disease......Page 118
Natural History and Progression of Chronic Kidney Disease......Page 119
Growth Failure......Page 120
Nutritional Issues and Metabolic Concerns......Page 123
Acid-Base and Electrolytes......Page 124
Neurocognitive Development and School Performance......Page 125
Anemia......Page 126
Mineral and Bone Disorders......Page 128
Phosphorus......Page 130
Vitamin D......Page 131
Hypertension......Page 132
Lipids......Page 133
Quality of Life and Transitions to Adulthood......Page 134
Congenital Nephrotic Syndrome......Page 143
Corticosteroid-Resistant Nephrotic Syndrome......Page 145
Corticosteroid-Sensitive Nephrotic Syndrome......Page 147
Autosomal Dominant Diseases......Page 149
Syndromic Proteinuric Kidney Disease......Page 151
X-Linked Diseases......Page 154
Autosomal Dominant Diseases (1)......Page 155
Sporadic Disease......Page 156
Treatment of Genetic Disease......Page 157
Introduction......Page 165
Philosophical Basis......Page 166
Role of Multidisciplinary Clinics......Page 167
Education......Page 168
Cardiovascular Disease......Page 169
Nutrition......Page 170
Diabetes Control......Page 171
Modality Selection......Page 172
Timely Initiation......Page 173
Transplant......Page 174
Key Components of the Clinic......Page 175
Chronic Kidney Disease Clinic Role in Longitudinal Care: Different Stages of Chronic Kidney Disease......Page 176
Other Benefits of the Chronic Kidney Disease Clinic and Organized Protocol-Based Care......Page 177
Recent and Future Studies......Page 178
Conclusion......Page 179
Pathogenesis......Page 186
Cognitive Function......Page 187
Erythropoiesis-Stimulating Agents......Page 188
Iron......Page 190
Data From Clinical Trials......Page 192
Erythropoiesis-Stimulating Agent Hyporesponsiveness......Page 193
Normal Physiology......Page 201
Abnormal Physiology in Chronic Kidney Disease......Page 202
Management of Elevated Phosphate in Chronic Kidney Disease......Page 203
Normal Physiology......Page 207
Abnormal Physiology in CKD......Page 208
Normal Physiology......Page 209
Management of Secondary Hyperparathyroidism......Page 210
Treatment of elevated parathyroid hormone in chronic kidney disease stage 5D: Calcitriol and vitamin D analogs.The use of calcit.........Page 211
FGF-23 in Chronic Kidney Disease......Page 212
Renal Osteodystrophy......Page 213
Cardiovascular Disease and Vascular Calcification in Chronic Kidney Disease......Page 214
Conclusion......Page 217
Vitamin D......Page 224
Vitamin D–Binding Protein......Page 225
Vitamin D Clearance......Page 226
Assessment of Vitamin D Deficiency......Page 227
Prevalence of Vitamin D Deficiency......Page 228
Autocrine and Paracrine Effects......Page 230
Cell Growth and Differentiation......Page 231
Glucose Metabolism......Page 232
Chronic Kidney Disease......Page 233
Cholecalciferol......Page 234
Ergocalciferol......Page 235
Unanswered Questions......Page 236
Conclusions......Page 237
Stage 3 to 4 Chronic Kidney Disease......Page 245
Dialysis......Page 247
Mechanisms of Cardiovascular Disease Risk in Chronic Kidney Disease......Page 248
Chronic Kidney Disease Stage 3 to 4......Page 249
Chronic Kidney Disease Stage 3 to 4......Page 251
Dialysis......Page 252
Left Ventricular Hypertrophy and Cardiomyopathy......Page 253
Therapy......Page 254
Nitric Oxide, Asymmetrical Dimethylarginine, and Endothelial Function......Page 255
Chronic Kidney Disease–Mineral Bone Disorder......Page 256
Pathophysiology and Manifestations: Atherosclerosis and Vascular Stiffness......Page 257
Diagnosis......Page 258
Heart Failure......Page 259
Treatment......Page 260
Aortic Calcification and Stenosis......Page 261
Ventricular Arrhythmias and Sudden Death......Page 262
Energy Requirements......Page 272
Protein Requirements......Page 273
Concept of Protein-Energy Wasting......Page 275
Testosterone deficiency and low thyroid hormone levels.Testosterone is an anabolic hormone that induces skeletal muscle hypertro.........Page 277
Prevalence of Protein-Energy Wasting in Chronic Kidney Disease......Page 278
Screening Tools......Page 279
Protein equivalent of nitrogen appearance.It is difficult to directly measure protein intake. Therefore an indirect marker used .........Page 280
Treatment of Protein-Energy Wasting in Chronic Kidney Disease......Page 281
Dietary Counseling and Use of Oral Nutritional Supplements......Page 282
Intradialytic Parental Nutrition......Page 283
Interventions to Reduce Inflammation......Page 284
Summary and Conclusions......Page 285
Chronic Inflammation: A Maladaptive Response in a Particular Setting......Page 291
Etiology of Inflammation in Chronic Kidney Disease......Page 292
Oxidative Stress......Page 293
Comorbidities......Page 294
Sleep apnea and hypoxia.The lung-kidney link has received very limited attention to date, although the mutual interrelations bet.........Page 295
Genetic Predisposition......Page 296
Consequences of Inflammation in Chronic Kidney Disease......Page 297
Vascular Calcification......Page 298
Endocrine Disorders......Page 299
Premature Senescence......Page 300
C-Reactive Protein......Page 301
Other Biomarkers of Inflammation......Page 302
Approaching a Patient With Inflammation......Page 303
Treating the Basics......Page 304
Novel antiinflammatory drugs.Within the search of novel therapies for reducing inflammation, controlling or reducing the amount .........Page 305
Conflict of Interest......Page 306
SLEEP IN CHRONIC KIDNEY DISEASE......Page 316
SLEEP IN END-STAGE KIDNEY DISEASE......Page 318
Sleep in Hemodialysis......Page 319
Sleep in Peritoneal Dialysis......Page 321
SLEEP IN PEDIATRIC CHRONIC KIDNEY DISEASE......Page 323
SLEEP IN KIDNEY TRANSPLANTATION......Page 325
CONCLUSIONS......Page 328
Chapter 16 - Depression and Neurocognitive Function in Chronic Kidney Disease......Page 333
Epidemiology of Depression......Page 334
Prevalence......Page 335
Immunological Response......Page 336
Substance Use......Page 337
Pharmacotherapy......Page 338
Summary of Depression in Chronic Kidney Disease......Page 339
Prevalence of Neurocognitive Impairment......Page 343
Sequelae of Neurocognitive Impairment......Page 344
Summary of Neurocognitive Function in Chronic Kidney Disease......Page 345
Chapter 17 - Improving Drug Use and Dosing in Chronic Kidney Disease......Page 352
Assessment of Kidney Function for Drug Dosing, Including Special Populations......Page 353
General Pharmacokinetic and Pharmacodynamic Principles......Page 355
Distribution......Page 356
Elimination......Page 357
General Approach for Drug Regimen Design in Chronic Kidney Disease......Page 358
Pharmacokinetics and Pharmacodynamics in Chronic Kidney Disease......Page 359
Pharmacokinetics and Pharmacodynamics in Chronic Kidney Disease......Page 361
Agents for Type 2 Diabetes Mellitus—Glucagon-Like Peptide-1 Receptor Agonists......Page 366
Drug Dosing in Dialysis Patients......Page 367
Considerations For Drug Removal by Renal Replacement Therapies......Page 368
Case Example: Dosing Brivaracetam in Hemodialysis and Continuous Kidney Replacement Therapy......Page 369
Q4: What If This Patient had Acute Kidney Injury and was Receiving Continuous Venovenous Hemofiltration With the Following Conti.........Page 370
Importance Of Interdisciplinary Teams in Improving Chronic Kidney Disease Care......Page 371
Informatics Approaches to Improve Chronic Kidney Disease Care......Page 372
Chapter 18 - The Pathophysiology of Uremia......Page 380
Classic Signs and Symptoms......Page 381
Uremia and Solute Retention......Page 382
Solute Production From Food......Page 383
Uremic Inflammation and Oxidative Stress......Page 385
Metabolomics Studies......Page 386
Uremic Solutes Associated With Adverse Clinical Outcomes......Page 387
GPCR (G-Protein Coupled Receptor) Signaling......Page 389
Extracorporeal Methods......Page 390
Conclusions......Page 391
Chapter 19 - Timing, Initiation, and Modality Options for Renal Replacement Therapy......Page 398
Past Kidney Disease Outcomes Quality Initiative Recommendations for Timing of Initiation of Dialysis......Page 399
Current Kidney Disease Outcomes Quality Initiative Recommendations for Timing of Initiation of Dialysis......Page 400
Other Clinical Practice Guidelines for Timing of Initiation of Dialysis......Page 401
Trends in Timing of Initiation of Dialysis......Page 402
Timeliness of Nephrology Referral......Page 403
Dialysis Modality Selection......Page 404
Peritoneal Dialysis......Page 405
Home Hemodialysis......Page 406
Conclusions......Page 407
Medical Ethics in Nephrology......Page 413
Advance Care Planning......Page 414
Conflict Resolution......Page 415
Providing Supportive (Palliative) Care......Page 417
End-of-Life Care......Page 418
Summary......Page 420
Causes of End-Stage Renal Disease and Indications for Maintenance Dialysis......Page 428
Incidence of Treated End-Stage Renal Disease......Page 430
Prevalence of ESRD......Page 431
Timing of Dialysis Initiation......Page 434
Mortality Trends in Patients Receiving Maintenance Dialysis......Page 436
Overall Trends......Page 438
Cardiovascular Disease: Implications for Morbidity and Mortality......Page 442
Infectious Diseases: Implications for Morbidity and Mortality......Page 447
Dialysis Modality......Page 448
Costs of End-Stage Renal Disease......Page 452
Conclusions......Page 454
Historical Development......Page 460
Clinical Syndrome......Page 461
Residual Syndrome......Page 463
Goals of Hemodialysis......Page 464
Laws of Diffusion......Page 465
Composition of the Membrane......Page 466
Blood Flow......Page 467
High-Efficiency and High-Flux Dialyzers......Page 468
Types of Clearance......Page 469
Quantifying Hemodialysis......Page 471
Kt/Vurea......Page 472
Urea Generation and Protein Catabolism......Page 473
Solute Disequilibrium......Page 474
Dialyzer Ultrafiltration Coefficient......Page 475
Middle and Large Molecule Removal......Page 476
Mechanics of Hemodialysis......Page 477
Bicarbonate Delivery......Page 478
Computer Controls......Page 479
Monitoring Access Flow......Page 480
Future Considerations......Page 481
Classification of Fistulas......Page 489
Life Cycle of the Arteriovenous Fistula......Page 490
Phase 3: Clinical Use, Initial......Page 491
Failure to Mature......Page 492
Excessive Flow......Page 493
Hand Ischemia: Dialysis Access Steal Syndrome......Page 495
Secondary Arteriovenous Fistulas......Page 496
Arteriovenous Graft......Page 497
Infection......Page 498
Hemodialysis Reliable Outflow Vascular Access Device......Page 500
Dialysis Catheters......Page 501
Adequacy of Dialysis......Page 502
Catheter Dysfunction......Page 504
Acute Dialysis Catheters......Page 505
Uremic Retention Solutes......Page 512
Mechanisms of Molecular Movement During Dialysis......Page 513
Collection of Blood Samples Before and After Hemodialysis......Page 514
Single-Pool Kt/V......Page 515
Equilibrated Kt/V......Page 516
Standard Kt/V......Page 517
Normalized Protein Catabolic Ratio......Page 518
Limitations of Urea-Based Measures of Dialysis Adequacy......Page 519
Key Studies of Optimal Dialysis Dose......Page 520
Factors Contributing to Infections Among Hemodialysis Patients......Page 525
Microbial Contamination of Water......Page 526
Distribution Systems......Page 527
Hemodialyzer Reuse......Page 528
Disinfection of Hemodialysis Systems......Page 533
Dialysis-Associated Pyrogenic Reactions......Page 534
Disinfection, Sterilization, and Environmental Cleaning in Dialysis Facilities......Page 535
Bloodstream Infections and Other Infections......Page 536
Etiology and Prevention of Bloodstream Infection......Page 537
Antimicrobial-Resistant Bacteria......Page 539
Hepatitis C Virus......Page 540
Prevention of Hepatitis C Virus Transmission......Page 541
Epidemiology......Page 542
Prevention of Hepatitis B Virus Transmission......Page 543
Summary of Recommendations and Future Directions......Page 544
Acknowledgments......Page 546
INVESTIGATING AN ADVERSE EVENT ON HEMODIALYSIS......Page 555
Reactions Associated With the Dialysis Circuit......Page 556
Reactions Associated With Drugs and Other Exposures......Page 557
Approach to the Dialysis Patient With a Reaction......Page 558
Muscle Cramps......Page 559
Headache......Page 560
Restless Legs Syndrome......Page 561
Seizures......Page 562
Intradialytic Hypertension......Page 563
Myocardial Stunning......Page 564
Dialysis-Associated Steal Syndrome......Page 565
Access Thrombosis......Page 566
Dialysis-Associated Hemolysis......Page 567
Hemorrhage......Page 568
Air Embolism......Page 569
Summary......Page 570
History of Frequent Hemodialysis......Page 577
Improved Clearance of Small Protein-Bound Solutes......Page 578
Survival......Page 579
Mineral Metabolism......Page 580
Noninfectious Vascular Complications......Page 581
Dialysis Machines......Page 582
Vascular Access......Page 583
Frequent Home Hemodialysis program......Page 584
Medication Dosing Considerations......Page 585
Future Directions......Page 586
Home Hemodialysis: Benefits and Potential Risks......Page 591
Left Ventricular Hypertrophy and Cardiovascular Complications......Page 592
Blood Pressure and Antihypertensive Medication Use......Page 593
Mineral and Bone Disorder and Phosphate Binder Use......Page 594
Health-Related Quality of Life......Page 596
Treatment Complications and Tolerability......Page 597
Potential Risks of Intensive Hemodialysis......Page 599
Patient Selection......Page 601
Dialysis Prescription......Page 602
Barrier to Home Dialysis......Page 603
Peritoneal Anatomy......Page 606
Interstitium......Page 607
Peritoneal Blood Flow......Page 608
Peritoneal Local Reaction to Infection......Page 609
Ultrafiltration......Page 610
Fluid Absorption......Page 612
Diffusive Transport......Page 613
Importance of Different Parts of the Peritoneum for Peritoneal Transport......Page 614
Peritoneal Equilibration Test......Page 615
Mini-PET and double mini-PET.Recently, a short 1-hour “mini-PET” with hypertonic 3.86% glucose (4.25% dextrose) solution was sug.........Page 616
Effluent Soluble Markers of the Peritoneal Membrane......Page 617
Effect of Body Posture on Peritoneal Transport......Page 618
Alternative Osmotic Agents......Page 619
Changes in Peritoneal Transport During Peritonitis......Page 620
Loss of Ultrafiltration Capacity......Page 621
Relation Between Peritoneal Transport Characteristics and Clinical Outcome......Page 622
Changes in Peritoneal Morphology With Time on Peritoneal Dialysis......Page 623
Physiological Mechanisms......Page 624
Identification of Potential Peritoneal Dialysis Patients......Page 632
Assessment of Peritoneal Dialysis Eligibility......Page 633
Offer and Choice......Page 634
Attempts at Randomized Comparisons of Peritoneal Dialysis and Hemodialysis......Page 635
Eligibility for Peritoneal Dialysis and Hemodialysis......Page 636
Setting......Page 637
Statistical Considerations......Page 638
Comparing the Outcomes of Patients Treated With Peritoneal Dialysis and Hemodialysis: Cost......Page 639
Summary......Page 640
Constituents of Peritoneal Dialysis Solutions......Page 646
Dialysate Calcium......Page 648
Local Effects......Page 649
Systemic Effects of Glucose-Based Peritoneal Dialysis Solutions......Page 650
Effects on metabolic profile.Use of icodextrin as the long-dwell solution also minimizes glucose exposure and incurs less metabo.........Page 651
Potential adverse effects.Use of icodextrin may be associated with potential adverse events such as sterile peritonitis or skin .........Page 652
Effects on peritonitis risk.In the balANZ trial, the time to first peritonitis episode was longer and overall peritonitis rates .........Page 653
Other clinical outcomes.Earlier studies suggested a potential benefit in reducing inflow pain with more biocompatible PD solutio.........Page 654
Amino Acid Peritoneal Dialysis Solutions......Page 657
Conclusions......Page 658
Measuring Biochemical Indices of Dialysis Adequacy......Page 659
Peritoneal Equilibration Test......Page 661
Importance of Dialysis Adequacy and Defining Numerical Targets for Biochemical Indices of Dialysis Adequacy......Page 662
Ultrafiltration and Volume Control as a Target for Dialysis Adequacy......Page 663
Nutrition Status as a Target for Dialysis Adequacy......Page 664
Initial Peritoneal Dialysis Prescription......Page 666
Adjusting Peritoneal Dialysis Prescription......Page 667
Factors Contributing to More Adverse Outcomes in High Transporters......Page 668
Ultrafiltration Failure......Page 669
Importance of Residual Kidney Function in Peritoneal Dialysis......Page 670
Decline of Residual Kidney Function......Page 672
Renin-angiotensin system blockers.The efficacy of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in p.........Page 673
Conclusion......Page 674
Pathogenesis......Page 684
Effects of Peritoneal Dialysis Solutions on Peritoneal Defense......Page 685
Empirical Therapy......Page 686
Adjuvant Therapy......Page 687
Gram-Negative Organisms.Peritonitis due to gram-negative organisms often is associated with fever, nausea, vomiting, and abdomin.........Page 688
Culture-Negative Peritonitis.In approximately 15% of episodes that meet the criteria for peritonitis on the basis of cell count .........Page 689
Complications of Peritoneal Dialysis Peritonitis......Page 690
Antibiotic Therapy......Page 691
Connectology and Dialysis Solutions......Page 692
Other Modifiable Risk Factors......Page 693
Secondary Prevention of Peritonitis......Page 694
Incidence, Types of Hernia, and Etiological Factors......Page 700
Clinical Presentation and Diagnosis......Page 701
Incidence, Classification of Leaks, and Risk Factors......Page 702
Complications of Dialysate Leaks......Page 703
Pathogenesis......Page 704
Clinical Presentation......Page 705
Temporary Interruption of Peritoneal Dialysis (Conservative Management).There is a clear consensus that interruption of PD shoul.........Page 706
Malfunction of the Peritoneal Catheter......Page 707
Drain Pain......Page 708
Hemoperitoneum......Page 709
Chyloperitoneum......Page 710
Hepatic Subcapsular Steatosis......Page 711
Definition and Epidemiology......Page 712
Pathophysiology......Page 713
Clinical Presentation and Diagnosis.EPS is a slowly progressive disorder that may remain asymptomatic for a prolonged period of .........Page 714
Corticosteroids.CCSs have become paramount in the treatment of EPS, with some studies documenting response rates as high as 100%.........Page 715
Immunotherapy and Other Experimental Agents.There are reports in the literature of immunosuppressants being used to treat EPS.18.........Page 716
Encapsulating Peritoneal Sclerosis and Renal Transplantation......Page 717
Introduction......Page 724
Living Donor Transplantation......Page 727
Induction Immunosuppression......Page 728
Maintenance Immunosuppression......Page 729
Posttransplant Outcomes......Page 732
Acute Rejection......Page 733
Effect of Performance Monitoring......Page 734
Unmeasured and Novel Risk Factors......Page 735
Economics of Kidney Transplantation......Page 736
Conclusions......Page 738
A. Transplantation Antigens......Page 745
B. Cellular Events Leading to Allograft Rejection......Page 748
Allorecognition Pathways......Page 749
T-Cell Activation......Page 751
Effector Mechanisms of Allograft Rejection......Page 756
Tolerance......Page 757
Summary......Page 759
Clinical Assessment of the Living Donor......Page 764
Proteinuria......Page 765
Inherited Renal Disease......Page 766
Pregnancy......Page 767
History, Physical Examination, and Diagnostic Testing......Page 768
Coronary Artery Disease......Page 770
Obstructive and Restrictive Lung Disease......Page 771
Hepatitis B......Page 772
Systemic Diseases......Page 773
History of a Failed Allograft......Page 774
Conclusions (1)......Page 775
Live Donor Evaluation......Page 778
Recipient Evaluation......Page 779
Surgical Technique......Page 780
Immediate Postoperative Management......Page 781
Transplant Renal Artery Stenosis......Page 782
Renal Vein Thrombosis......Page 783
Urinary Obstruction......Page 784
Surgical Site Infection......Page 785
Conclusions......Page 786
The Azathioprine Era (1962–1980)......Page 790
Contemporary Immunosuppressive Therapy......Page 791
Landmark Trials With Induction Therapy......Page 793
Calcineurin Inhibitors......Page 794
Combination Therapies and Trials That Led to Current Standards......Page 795
CNI-Sparing Therapies......Page 796
Looking Forward......Page 801
Conclusion......Page 803
Definition......Page 807
Differential Diagnosis......Page 808
Prediction and Prevention of Delayed Graft Function......Page 809
Diagnostic Studies in Persistent Oliguria or Anuria......Page 810
Long-Term Impact of Immediate Graft Dysfunction......Page 811
Types of Acute Rejection......Page 812
Noninvasive Diagnostic Biomarkers......Page 813
Thrombotic Microangiopathy......Page 814
Renal Artery Stenosis......Page 815
Late Graft Dysfunction......Page 816
Antigen-Dependent Causes of Late Graft Loss......Page 817
Histocompatibility......Page 818
Histopathological Features of Chronic Graft Dysfunction......Page 819
Strategies to Prevent Late Graft Loss (Also See Chapter 44)......Page 820
BK Nephropathy......Page 821
Acknowledgments......Page 822
Pretransplant Recipient Evaluation......Page 827
Donor Evaluation......Page 829
Timeline of Infection......Page 830
Beyond 6 Months......Page 832
Patterns of transmission......Page 833
Prevention......Page 834
Diagnosis of Epstein-Barr Virus and Posttransplant Lymphoproliferative Disease......Page 835
Treatment......Page 836
Use of Hepatitis C Virus-positive Donors......Page 837
Hepatitis B......Page 838
Human Immunodeficiency Virus......Page 839
Use of Human Immunodeficiency Virus-positive Donors......Page 840
Cryptococcus......Page 841
Bacterial Infections......Page 842
Immunization......Page 843
Cardiovascular Disease......Page 851
Hypertension......Page 852
Dyslipidemia......Page 853
Obesity......Page 854
Posttransplantation Anemia......Page 855
Malignancy After Kidney Transplantation......Page 856
Effect of Immunosuppression......Page 857
Electrolyte Disorders......Page 858
Treatment of Posttransplant Osteopenia and Osteoporosis......Page 859
Neuropsychiatric Complications of Transplantation......Page 860
Psychopharmacology......Page 861
Summary and Conclusion......Page 862
The Effect of Recurrent or De Novo Disease on Transplant Outcome......Page 868
Focal Segmental Glomerulosclerosis......Page 870
Membranous Nephropathy......Page 871
Membranoproliferative Glomerulonephritis and C3 Glomerulopathy......Page 872
Antineutrophil Cytoplasmic Antibody-Associated Vasculitis......Page 873
Hemolytic Uremic Syndrome and Other Thrombotic Microangiopathies......Page 874
Multiple Myeloma/Cast Nephropathy......Page 875
Fabry Disease......Page 876
Sickle Cell Disease......Page 877
Role of Transplantation......Page 884
Indications for Renal Transplantation in Children......Page 885
Urological Preparation......Page 886
Technical Issues in Transplantation......Page 887
Graft Thrombosis......Page 888
Immunosuppression Strategies......Page 889
Acute Rejection......Page 890
Chronic Allograft Dysfunction......Page 891
Hemolytic Uremic Syndrome......Page 892
Graft Survival......Page 893
Growth After Transplantation......Page 894
Posttransplant Lymphoproliferative Disorder and Malignancy......Page 895
Varicella......Page 896
Hyperlipidemia/Dyslipidemia......Page 897
Mortality......Page 898
Section V - Acute Kidney Injury......Page 906
Prevalence of Chronic Kidney Disease in Kidney Transplant Recipients......Page 908
The Predictive Value of Chronic Kidney Disease Staging for Outcomes Among Kidney Transplant Recipients......Page 909
Chronic Kidney Disease Care in Patients With a Functioning Allograft......Page 910
Chronic Kidney Disease Care in Patients With Transplant Failure......Page 911
Definition of Acute Kidney Injury......Page 916
Early Cohort Studies of Acute Kidney Injury......Page 917
Multicenter Cohort Studies of Acute Kidney Injury......Page 918
Large Database Studies of Acute Kidney Injury......Page 919
Risk Factors for the Development of Acute Kidney Injury......Page 920
Risk Factors for Mortality Associated With Acute Kidney Injury......Page 925
Long-Term Implications of an Episode of Acute Kidney Injury......Page 927
Summary......Page 929
Prevalence of Protein-Engery Wasting in Acute Kidney Injury......Page 934
Inflammation......Page 935
Oxidative Stress......Page 937
Animal Models of Oxidative Stress in Acute Kidney Injury......Page 938
Growth Hormone and Insulin-like Growth Factor I Axis......Page 939
Insulin Resistance in Acute Kidney Injury......Page 940
Insulin Resistance......Page 941
Provision of Nutritional Support......Page 943
Protein Requirement......Page 944
“Immunonutrition,” Micronutrients, and Other Additives......Page 945
Route......Page 946
Timing......Page 947
Conclusion......Page 948
Biomarkers in Acute Kidney Injury......Page 955
Creatinine as a Biomarker......Page 956
Specific Biomarkers of Acute Kidney Injury......Page 957
Interleukin-18......Page 958
Neutrophil Gelatinase-Associated Lipocalin......Page 959
Liver Type Fatty Acid-Binding Protein......Page 960
Kidney Injury Molecule-1......Page 961
Tissue Inhibitor of Metalloproteinase 2 and Insulin-Like Growth Factor-Binding Protein 7......Page 962
Uromodulin......Page 963
Repurposed Biomarkers......Page 964
The Future of Biomarkers in Acute Kidney Injury......Page 965
Disclosures......Page 966
Chapter 48 - Pharmacological Interventions in Acute Kidney Injury......Page 972
Acute Kidney Injury Is a Multisystem Disease......Page 973
Diuretics......Page 974
Antioxidants: N-Acetylcysteine, Vitamin C......Page 975
Dopamine, Dopamine Analogs, and Natriuretic Peptides......Page 977
Vasopressin and Analogs......Page 978
Recombinant Erythropoietin......Page 979
α-Melanocyte–Stimulating Hormone......Page 980
Soluble Thrombomodulin......Page 981
Adenosine Triphosphate–Sensitive K Channel Agonists......Page 982
Mitochondrial Agents......Page 983
Mesenchymal Stem Cell Therapy......Page 984
Disclosures......Page 985
Modalities of Renal Replacement Therapy......Page 999
Continuous Modalities......Page 1001
Continuous Renal Replacement Therapy......Page 1002
Timing of Initiation of Renal Replacement Therapy......Page 1003
Selection of Modality of Renal Replacement Therapy......Page 1005
Dose of Renal Replacement Therapy......Page 1006
Intermittent Hemodialysis and Prolonged Intermittent Renal Replacement Therapy......Page 1007
Continuous Renal Replacement Therapy......Page 1008
Summary and Recommendations......Page 1009
Anticoagulation......Page 1010
Procedure-Related Complications......Page 1012
Summary......Page 1013
A......Page 1022
B......Page 1024
C......Page 1025
D......Page 1028
E......Page 1030
F......Page 1031
G......Page 1032
H......Page 1033
I......Page 1035
K......Page 1036
L......Page 1037
N......Page 1038
O......Page 1039
P......Page 1040
R......Page 1042
S......Page 1044
T......Page 1045
V......Page 1046
Z......Page 1047

Citation preview

Chronic Kidney Disease, Dialysis, and Transplantation A Companion to Brenner and Rector’s The Kidney FOURTH EDITION

Jonathan Himmelfarb, MD Professor of Medicine Director, Kidney Research Institute Co-Director, Center for Dialysis Innovation Joseph W. Eschbach MD Endowed Chair for Kidney Research Department of Medicine, Division of Nephrology University of Washington

T. Alp Ikizler, MD Director, Division of Nephrology Catherine McLaughlin-Hakim Chair in Vascular Biology Professor of Medicine Department of Medicine, Vanderbilt University Medical Center Nashville, Tennessee

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

CHRONIC KIDNEY DISEASE, DIALYSIS, AND TRANSPLANTATION, FOURTH EDITION 

ISBN: 978-0-323-52978-5

Copyright © 2019 by Elsevier, Inc. All rights reserved. Chapter 25 Hemodialysis-Associated Infections, contributed by Duc B. Nguyen, Matthew J. Arduino and Priti R. Patel, is in Public Domain. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

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SECTION EDITORS Roy D. Bloom, MD Professor of Medicine University of Pennsylvania; Medical Director Penn Kidney Pancreas Transplant Program Philadelphia, Pennsylvania Rajnish Mehrotra, MD Professor of Medicine Section Head, Nephrology Harborview Medical Center University of Washington Seattle, Washington

Sushrut S. Waikar, MD, MPH Constantine L. Hampers, MD Distinguished Chair in Renal Medicine Director of Translational Research and Ambulatory Services, Renal Division Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, Massachusetts

Katherine R. Tuttle, MD, FASN, FACP Executive Director for Research Providence Health Care; Regional Co-Principal Investigator, Clinical Professor of Medicine Institute of Translational Health Sciences University of Washington Spokane, Washington

v

LIST OF CONTRIBUTORS Sophoclis Alexopoulos, MD, FACS

Joanne M. Bargman, MD, FRCPS

Juan J. Carrero, PhD, MBA

Associate Professor Department of Surgery Vanderbilt University Medical Center Nashville, Tennessee

Division of Nephrology Department of Medicine University Health Network Toronto, Ontario, Canada

Associate Professor Department of Medical Epidemiology and Biostatics Karolinska Institutet Stockholm, Sweden

Tarek Alhamed, MD, MS

Gerald A. Beathard, MD, PhD, FASN

Medical Director, Kidney and Pancreas Transplant Program Assistant Professor Washington University School of Medicine St. Louis, Missouri

Clinical Professor of Medicine University of Texas Medical Branch Galveston, Texas

Esteban Cedillo-Couvert, MD

Monica C. Beaulieu, MD, FRCPC, MHA

Christopher T. Chan, MD

St. Paul’s Hospital; University of British Columbia Vancouver, British Columbia, Canada

Director of Nephrology University Health Network Toronto, Ontario, Canada

Justin M. Belcher, MD, PhD

Anil Chandraker, MD, FRCP

Instructor Department of Internal Medicine Section of Nephrology Yale University School of Medicine New Haven, Connecticut; Instructor Department of Internal Medicine Section of Nephrology VA Connecticut Healthcare System West Haven, Connecticut

Associate Professor Transplantation Research Center Renal Division Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts

Radica Z. Alicic, MD, FHM, FACP Providence Health Care University of Washington School of Medicine Spokane, Washington

Amatur Amarah, MD John H. Stroger, Jr., Hospital of Cook County Chicago, Illinois

Shubha Ananthakrishnan, MD Associate Clinical Professor Department of Internal Medicine University of California, Davis School of Medicine; Medical Director Southgate Dialysis Clinic; Medical Director University Home Dialysis Clinic Sacramento, California

Jeffrey S. Berns, MD Renal, Electrolyte, and Hypertension Division Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

Matthew J. Arduino, MS, DrPH

Scott D. Bieber, DO

Senior Advisor for Environmental Hygiene and Infection Prevention Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, Georgia

Department of Medicine University of Washington Seattle, Washington

Deborah S. Rosenthal Asher, PhD Memory and Psychological Services, Inc. Brecksville, Ohio

Roy D. Bloom, MD Professor of Medicine University of Pennsylvania; Medical Director Penn Kidney Pancreas Transplant Program Philadelphia, Pennsylvania

David Axelrod, MD, MBA Surgical Director of Kidney, Pancreas, and Living Donor Transplant Division of Transplant and Hepatobiliary Surgery University of Iowa Iowa City, Iowa

Emily A. Blumberg, MD Professor of Medicine Perelman School of Medicine Infectious Diseases Division Department of Medicine Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

Rasheed Abiodun Balogun, MBBS, FACP Professor of Medicine Division of Nephrology Department of Medicine University of Virginia Charlottesville, Virginia

vi

South Texas Renal Care Group San Antonio, Texas

Tushar Chopra, MD, MBBS, FASN Assistant Professor of Medicine Department of Medicine Division of Nephrology University of Virginia Charlottesville, Virginia

Gabriela Cobo, MD, PhD Department of Education and Research Hospital Eugenio Espejo Quito, Equador

Lewis M. Cohen, MD Professor of Psychiatry University of Massachusetts-Baystate; Consultation Psychiatrist Baystate Medical Center Springfield, Massachusetts

Allan J. Collins, MD Director Chronic Disease Research Group Minneapolis Medical Research Foundation; Professor Department of Medicine University of Minnesota Minneapolis, Minnesota

Beatrice P. Concepcion, MD Brendan Bowman, MD Assistant Professor of Medicine Division of Nephrology University of Virginia Health System Charlottesville, Virginia

Assistant Professor of Medicine Division of Nephrology Vanderbilt University Nashville, Tennessee

LIST OF CONTRIBUTORS

Michael J. Connor Jr., MD

John S. Gill, MD, FRCPC, MS, FAST

Lesley A. Inker, MD, MS

Associate Professor of Medicine Emory University Atlanta, Georgia

Professor of Medicine Division of Nephrology University of British Columbia Vancouver, British Columbia

Division of Nephrology Tufts Medical Center Boston, Massachusetts

Josef Coresh, MD, MHS, PhD Professor of Epidemiology, Biostatistics & Medicine Johns Hopkins University Director, George W. Comstock Center for Public Health Research and Prevention Director, Cardiovascular Epidemiology Training Program Baltimore, Maryland

vii

Magdalena Jankowska, MD, PhD Simin Goral, MD Professor of Medicine Perelman School of Medicine Renal, Electrolyte, and Hypertension Division Department of Medicine Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

Department of Nephrology Transplantology, and Internal Medicine Medical University of Gdańsk Gdańsk, Poland

Emily J. Johnson, PhD Providence Health Care Spokane, Washington

Daniel Cukor, PhD Department of Psychiatry SUNY Downstate Medical Center Brooklyn, New York

Solomon Dawson, MD Nephrology Fellow Renal, Electrolyte, and Hypertension Division Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

Monica Grafals, MD, MPH Associate Professor Clinical Practice, Medicine-Renal Med Diseases/Hypertension University of Colorado, Anschutz Campus Aurora, Colorado

Clare B. Jones, MB, ChB

St. Paul’s Hospital; Vancouver General Hospital Vancouver, British Columbia, Canada

Clinical Fellow Nephrology University Health Newtowrk Toronto, Ontario, Canada

Professor of Medicine Adjunct Professor of Epidemiology Division of Nephrology University of Washington Seattle, Washington

Gentzon Hall, MD, PhD

Michelle Denburg, MD, MS

Olof Heimbürger, MD, PhD

Assistant Professor Pediatrics and Epidemiology The Children’s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Senior Consultant Patient Area Endocrinology and Renal Medicine Karolinska University Hospital; Associate Professor Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm, Sweden

Professor Emeritus Department of Internal Medicine University of California, Davis School of Medicine Sacramento, California

Vikas R. Dharnidharka, MD, MPH Professor and Chief Division of Pediatric Nephrology Washington University School of Medicine St Louis Children’s Hospital St Louis, Missouri

Michael J. Germain, MD Professor of Medicine University of Massachusetts-Baystate; Nephrologist Baystate Medical Center Springfield, Massachusetts

Clinical Associate Professor of Medicine Division of Nephrology University of British Columbia Vancouver, British Columbia

Judi M. Graham, MBBChBAO

Ian de Boer, MD, MS

Thomas A. Depner, MD

Olwyn Johnston, MB, MRCPI, MD, MHSc

Assistant Professor of Medicine Duke Molecular Physiology Institute Duke University School of Medicine Durham, North Carolina

Sangeeta R. Hingorani, MD, MPH Division of Nephrology, Department of Pediatrics Seattle Children’s Hospital and University of Washington Seattle, Washington

Anna Jovanovich, MD University of Colorado School of Medicine Division of Renal Disease and Hypertension Aurora, Colorado

Philip Kam-Tao Li, MD, FRCP, FACP Consultant and Honorary Professor Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong, China

Seth J. Karp, MD Professor and Chairman Department of Surgery Vanderbilt University Medical Center Nashville, Tennessee

Jessica Kendrick, MD, MPH University of Colorado School of Medicine Division of Renal Disease and Hypertension Aurora, Colorado

Joanna Q. Hudson, PharmD Professor Departments of Clinical Pharmacy & Translational Science and Medicine (Nephrology) The University of Tennessee Health Science Center Memphis, Tennessee

Paul L. Kimmel, MD, MACP Department of Medicine George Washington University Medical Center Washington, DC

Derk C.F. Klatte, MD Leiden University Medical Center Leiden, The Netherlands

viii

LIST OF CONTRIBUTORS

Greg Knoll, MD, MSc, FRCPC

Helen MacLaughlin, BSc, PhD

Mark Douglas Okusa, MD, FASN

Head, Division of Nephrology University of Ottawa and the Ottawa Hospital Ottawa, Canada

Department of Nutrition and Dietitics King’s College Hospital London, United Kingdom

Professor of Medicine Chief, Division of Nephrology University of Virginia Charlottesville, Virginia

Michael A. Kraus, MD

Nicola Marsh, BSc, MSc

Professor of Clinical Medicine Department of Nephrology Indiana University Indianapolis, Indiana; Senior Medical Advisor NxStage Kidney Care Lawrence, Massachusetts

Department of Nutrition and Dietetics King’s College Hospital London, United Kingdom

James P. Lash, MD The University of Illinois at Chicago Division of Nephrology, Department of Medicine Chicago, Illinois

Krista L. Lentine, MD, PhD Professor of Medicine, Director of Living Donation Center for Abdominal Transplantation Saint Louis University School of Medicine St. Louis, Missouri

Andrew S. Levey, MD Division of Nephrology Tufts Medical Center Boston, Massachusetts

Adeera Levin, MD, FRCPC St. Paul’s Hospital; University of British Columbia Vancouver, British Columbia, Canada

Mary Ann Lim, MD Assistant Professor of Clinical Medicine PENN Transplant Institute Renal, Electrolyte, and Hypertension Division Perelman School of Medicine Philadelphia, Pennsylvania

Bengt Lindhom, MD, PhD Adjunct Professor Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology Karolinska Institutet Stockholm, Sweden

Kathleen Liu, MD, PhD, MAS Professor Departments of Medicine and Anesthesia University of California, San Francisco San Francisco, California

Department of Medicine University of Toronto Toronto, Ontario, Canada

Lea Matsuoka, MD, FACS Associate Professor Department of Surgery Vanderbilt University Medical Center Nashville, Tennessee

Habib Mawad, MD, FRCPC Clinical Assistant Professor University of Montreal Postdoctoral Fellow University of British Columbia Vancouver, British Columbia

Paul M. Palevsky, MD Professor of Medicine University of Pittsburgh; Chief, Renal Section VA Pittsburgh Healthcare System Pittsburgh, Pennsylvania

Chirag R. Parikh, MD, PhD Director, Division of Nephology Ronald Peterson Professor of Medicine Johns Hopkins School of Medicine Baltimore, Maryland

Rajnish Mehrotra, MD, MS Professor of Medicine Section Head, Nephrology Harborview Medical Center University of Washington Seattle, Washington

Priti R. Patel, MD, MPH

Sharon Moe, MD

Anna C. Porter, MD

Stuart A. Kleit Professor of Medicine and Director, Division of Nephrology Department of Medicine, Division of Nephrology Indiana University School of Medicine Indianapolis, Indiana

The University of Illinois at Chicago Division of Nephrology, Department of Medicine Chicago, Illinois

Philip Kam-Tao Li, MD, FRCP, FACP Consultant and Honorary Professor Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong, China

Matthew J. Oliver, MD, MHS

Nadar Najafian, MD Lecturer on Medicine Renal Division Harvard Medical School Boston, Massachusetts; Director, Clinical Research Alnylam Pharmaceuticals Cambridge, Massachusetts

Melissa Nataatmadja, MBBS, MPH&TM, FRACP St. Paul’s Hospital; Vancouver General Hospital Vancouver, British Columbia, Canada

Duc B. Nguyen, MD Service Fellow Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, Georgia

Medical Officer Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, Georgia

Robert R. Quinn, MD, PhD Departments of Medicine & Community Health Sciences University of Calgary Calgary, Canada

Leonardo V. Riella, MD, PhD Assistant Professor of Medicine, Associate Physician Medicine Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts

Eugene P. Rhee, MD Nephrology Division Massachusetts General Hospital Boston, Massachusetts

Matthew B. Rivara, MD Clinical Assistant Professor Division of Nephrology University of Washington; Investigator Kidney Research Institute Seattle, Washington

LIST OF CONTRIBUTORS

Mitchell H. Rosner, MD

Anand Srivastava, MD, MPH

Mark L. Unruh, MD, MS

Professor of Medicine Division of Nephrology University of Virginia Health System Charlottesville, Virginia

Assistant Professor of Medicine Center for Translational Metabolism and Health Institute for Public Health and Medicine Division of Nephrology and Hypertension Northwestern University Feinberg School of Medicine Chicago, Illinois

Professor and Chair Department of Internal Medicine University of New Mexico Albuquerque, New Mexico

Maria-Eleni Roumelioti, MD Research Assistant Professor Division of Nephrology Department of Internal Medicine University of New Mexico Albuquerque, New Mexico

Athanasios K. Roumeliotis, MD Nephrology Toronto General Hospital Toronto, Ontario, Canada

Michelle C. Starr, MD, MPH Division of Nephrology, Department of Pediatrics Seattle Children’s Hospital and University of Washington Seattle, Washington

Chief, Division of Nephrology Tufts Medical Center Boston, Massachusetts

Deirdre Sawinski, MD Assistant Professor of Medicine Perelman School of Medicine Renal, Electrolyte, and Hypertension Division Department of Medicine Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

Professor Division of Renal Medicine, Department of Clinical Science, Intervention, and Technology Karolinska Institutet Stockholm, Sweden

Professor Department of Pharmaceutical Care and Health Systems University of Minnesota College of Pharmacy Minneapolis, Minnesota

Professor Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin, Hong Kong, China

Ashita J. Tolwani, MD, MS Professor of Medicine University of Alabama at Birmingham Birmingham, Alabama

Emilie Trinh, MD Neil Sheerin, MBBS, PhD, FRCP Professor of Nephrology Newcastle University Newcastle upon Tyne, United Kingdom

Edward D. Siew, MD, MSCI Associate Professor of Medicine Division of Nephrology and Hypertension Vanderbilt University Medical Center; Tennessee Valley Health Systems Nashville Veterans Affairs Hospital Nashville, Tennessee

Constantine L. Hampers, MD Distinguished Chair in Renal Medicine Director of Translational Research and Ambulatory Services, Renal Division Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, Massachusetts

Angela Yee-Moon Wang, MD, PhD Hon. Associate Professor Associate Consultant Department of Medicine University of Hong Kong, Queen Mary Hospital Hong Kong, China

Cheuk-Chun Szeto, MD, FRCP

Tariq Shafi, MBBS, MHS Associate Professor of Medicine Division of Nephrology The Johns Hopkins University School of Medicine Baltimore, Maryland

Director of Nephrology & Transplantation Department of Medicine Maine Medical Canter Portland, Maine; Associate Professor of Medicine Tufts University School of Medicine Boston, Massachusetts

Wendy L. St. Peter, PharmD

Heidi Schaefer, MD Associate Professor of Medicine Division of Nephrology Vanderbilt University Nashville, Tennessee

John P. Vella, MD, FACP, FRCP, FASN, FAST

Sushrut S. Waikar, MD, MPH Peter Stenvinkel, MD, PhD

Mark J. Sarnak, MD, MS

ix

Division of Nephrology McGill University Health Center Montreal, Quebec, Canada

Katherine R. Tuttle, MD, FACP, FASN, FNKF Executive Director for Research Providence Health Care; Regional Co-Principal Investigator, Clinical Professor of Medicine Institute of Translational Health Sciences University of Washington Spokane, Washington

Monnie Wasse, MD, MPH, FASN Director, Interventional Nephrology Professor of Medicine Department of Medicine Rush University Medical Center Chicago, Illinois

Lori Wazny, BSc, PharmD Extended Practice Pharmacist Manitoba Renal Program Health Sciences Centre Winnipeg, Manitoba, Canada

Daniel E. Weiner, MD, MS Nephrologist Tufts Medical Center; Associate Professor of Medicine Tufts University School of Medicine Boston, Massachusetts

x

LIST OF CONTRIBUTORS

Eric Weinhandl, PhD, MS

Tiffany C. Wong, MD

Jane Y. Yeun, MD

Adjunct Assistant Professor Department of Pharmaceutical Care and Health Systems University of Minnesota Minneapolis, Minnesota; Clinical Epidemiologist NxStage Medical Lawrence, Massachusetts

Nephrology Fellow Renal, Electrolyte, and Hypertension Division Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

Clinical Professor Department of Internal Medicine University of California, Davis School of Medicine Sacramento, California; Staff Nephrologist Sacramento Veterans Administration Medical Center Department of Medicine Mather, California

Tyler B. Woodell, MD Oregon Health & Science University Portland, Oregon

Jessica W. Weiss, MD, MCR Oregon Health & Science University Portland, Oregon

James B. Wetmore, MD, MS Associate Professor of Medicine University of Minnesota School of Medicine; Staff Nephrologist Division of Nephrology Hennepin County Medical Center Minneapolis, Minnesota

Hong Xu, MD Department of Medical Epidemiology and Biostatics Karolinska Institutet Stockholm, Sweden

Nadia Zalunardo, MD, SM, FRCPC Vancouver General Hospital; University of British Columbia Vancouver, British Columbia, Canada

1 Chronic Kidney Disease: Definition, Epidemiology, Cost, and Outcomes Tariq Shafi, MBBS, MHS, and Josef Coresh, MD, MHS, PhD OUTLINE Definition and Staging of Chronic Kidney Disease, 2 Definition, 2 Staging, 3 Strengths and Limitations of the Current Chronic Kidney Disease Classification System, 5 Epidemiology of Chronic Kidney Disease, 6 Etiology of Chronic Kidney Disease, 7 Prevalence and Incidence of Chronic Kidney Disease, 7 Prevalence and Incidence of Kidney Failure, 12

Costs of Chronic Kidney Disease, 14 Chronic Kidney Disease (Not on Kidney Replacement Therapy) Costs, 14 End-Stage Renal Disease Costs, 15 Outcomes of Chronic Kidney Disease, 15 Outcomes Before Kidney Replacement Therapy, 17 Outcomes on Kidney Replacement Therapy, 20

Chronic kidney disease (CKD) is a global public health problem. CKD is defined based on the presence of kidney damage or reduced glomerular filtration rate (GFR), which is considered the best overall index of kidney function.1,2 CKD staging is based on its cause, the GFR level, and degree of albuminuria. The past 20 years have seen significant improvement in recognition of the incidence, prevalence, and complications of CKD due in major part to the standardized definition and staging of CKD in 2002. The global adoption of this approach to CKD, with its emphasis on routine and automated estimation of GFR (eGFR) from serum creatinine, has improved recognition of CKD in many populations and settings where it was previously underrecognized. Increased awareness of CKD and uniform classification criteria also has led to a better understanding of the burden of illnesses that accompany CKD, an increased focus on developing methods to slow CKD progression, and a stronger emphasis on early recognition and prevention of complications associated with CKD. Fig. 1.1 shows a conceptual diagram emphasizing the importance of looking at both progression of CKD itself, from normal to damaged without reduced GFR, to reduced GFR, to kidney failure and death (horizontal progression), as well as risk for complications that can lead to mortality. Complications outside the kidney, particularly cardiac and metabolic complications are important as they often lead to death before the onset of kidney replacement therapy (KRT) with dialysis or transplantation.

In the following sections, we will review the epidemiology, cost, and outcomes of CKD, emphasizing advances in knowledge over the past decade.

Acknowledgment: The authors thank Eugenia Shing Yu Wong, BSc, for assistance with making figures and editing the chapter.

2

DEFINITION AND STAGING OF CHRONIC KIDNEY DISEASE CKD is a general term for a number of heterogeneous disorders that result in sustained kidney damage with implications for the health of the individual. The initial decline of kidney function is asymptomatic and clinical manifestations of kidney failure occur late in the course of the disease. Definitions of kidney disease therefore include measures of function (e.g., GFR) and measures of damage (e.g., proteinuria, anatomical abnormalities).

Definition Before the Kidney Disease Outcomes Quality Index (KDOQI) guidelines in 2002, there were numerous definitions of CKD in use. Many of these definitions were not well understood by patients and the lay public due to the use of word renal and its Latin and Greek roots. Hsu and Chertow enumerated the different names used for CKD from abstracts submitted to the American Society of Nephrology (ASN) meetings in 1998 and 1999 as well as from articles indexed in Medline.3 They noted 23 different terms used to describe states of reduced GFR along with a number of different and overlapping definitions of kidney failure using serum creatinine, creatinine clearance, or GFR. Considering these and other factors, the 2002 KDOQI working group decided on using the word kidney instead of renal and developed an operational uniform

CHAPTER 1  Chronic Kidney Disease: Definition, Epidemiology, Cost, and Outcomes

3

Complications

Normal

Increased risk

Damage

↓ GFR

Kidney failure

Death

FIG. 1.1  Conceptual model of renal decline. (From Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011;80(1):17-28.)

TABLE 1.1A  Definition of Chronic Kidney

Disease 1.

2.

Criteria (either one of the following for > 3 months) Markers of Kidney Damage (One or More): • Albuminuria (AER ≥30 mg/24 h; ACR ≥30 mg/g [≥3 mg/mmol]) • Urine sediment abnormalities • Electrolyte and other abnormalities due to tubular disorders • Abnormalities detected by histology • Structural abnormalities detected by imaging • History of kidney transplantation Decreased GFR • GFR 3 months, with implications for health. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) group provides a clear CKD definition (Table 1.1A) and its operational criteria (Table 1.1B).2,7 The key elements of this definition include chronicity (>3 months), presence of kidney damage, decreased GFR, and implications for health. The chronicity component of the definition (>3 months) is arbitrarily defined to distinguish CKD from acute kidney injury (AKI). The chronicity component, implies but does not necessitate, irreversibility. Presence of kidney damage can be inferred by the presence of albuminuria, abnormal urinary sediment such as hematuria or casts, functional disorders such renal tubular acidosis or nephrogenic diabetes insipidus, pathological abnormalities detected on kidney biopsy such as immunoglobulin (Ig)A nepthropathy, or structural abnormalities of the kidney such as polycystic kidney disease. Decreased GFR is a manifestation of kidney damage from underlying renal pathology. The KDIGO 2012 guidelines kept

the GFR at the 2200 mg/g creatinine) should be considered as nephrotic-range proteinuria, roughly corresponding to urinary protein excretion >3500 mg/day. The guidelines recognized that the use of only three categories for albuminuria

TABLE 1.1B  Criteria for Definition of Chronic Kidney Disease. Criteria 1. Duration >3 months, based on documentation or inference 2. GFR 1 mg/mmol) • Urine ACR 30-300 mg/g (3–30 mg/mmol; category A2) generally corresponds to ‘‘microalbuminuria,’’ now referred to as ‘‘moderately increased’’ • Urine ACR ≥300 mg/g (≥30 mg/mmol; category A3) generally corresponds to ‘‘macroalbuminuria,’’ now termed ‘‘severely increased’’ • Urine ACR 60 mL/min/1.73 m2 (GFR categories G1-G2) and ACR is 30mg/mmol

54.7

4.3

0.4

59.5

60–89

30.4

2.6

0.3

33.3

45–59

3.9

0.9

0.2

5.0

30–44

1.0

0.5

0.2

1.7

15–29

0.1

0.1

0.2

0.4