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Clinical Approach to Renal Diseases in Diabetes
T Dhinakaran
CHAPTER 1:
Diabetes Mellitus— A Worldwide Health Challenge
INTRODUCTION
THE INDIAN SCENARIO
REASONS BEHIND THE RISING TREND IN INDIANS
Genetic Reasons
Asian Indian Phenotype
Thin Fat Phenotype
Thrifty Phenotype
The Epidemiological Factors
Rural versus Urban Living
Socioeconomic Status
Sedentary Lifestyle
The Role of Central Obesity
PREVENTION OF TYPE 2 DIABETES—SOME USEFUL STEPS
Lifestyle Changes
Role of Exercise
Weight Loss
Metformin—DPP Trial
Glitazones—DREAM Trial
Alpha-Glucosidase Inhibitors
Angiotensin-converting Enzyme Inhibitors and Angiotensin Receptor Blockers
WHAT IS OUR PROGRESS?
Evidences Included
Essential at a Glance
CHAPTER 2:
Diabetes and Kidney— Diabetic Kidney Disease
INTRODUCTION
THE TERMINOLOGY
INDIAN STUDIES SHOWING INCIDENCE OF COMPLICATIONS OF DIABETES
CLINICAL STAGES OF DIABETIC GLOMERULOPATHY
Development of Diabetic Kidney Disease
Stage 1—Hyperfiltration-Hypertrophy Stage
Stage 2—Structural Changes without Functional Alterations
Stage 3—Incipient Nephropathy
Stage 4—Overt Clinical Nephropathy
Stage 5—End-stage Renal Failure
Predictor of Progression beyond Proteinuria
CHAPTER 3:
Risk Factors for Diabetic Nephropathy
INTRODUCTION
RISK FACTORS FOR DIABETIC NEPHROPATHY
Duration of Diabetes
Long-Term Risk of Diabetic Nephropathy
Familial and Genetic Factors
Genetics in Diabetic Nephropathy
Familial Aggregation of Diabetic Nephropathy
Familial Aggregation of End-Stage Renal Disease and Heritability of Declining Glomerular Filtration Rate
Genome Scans for Genes of Diabetic Nephropathy
Genome Scans for End-Stage Renal Disease or Variation in Glomerular Filtration Rate
Candidate Genes for Diabetic Nephropathy
Genomics in Diabetic Nephropathy
Hyperglycemia
High Blood Pressure
Dyslipidemia
Proteinuria
Smoking
CHAPTER 4:
Is Diabetic Nephropathy Preventable?
THE EARLY CLINICAL COURSE OF DIABETIC NEPHROPATHY
PREVENTION OF MICROALBUMINURIA—RENIN ANGIOTENSIN SYSTEM–INHIBITOR THERAPY
Type 1 Diabetes
Glycemic Control for the Prevention of Diabetic Nephropathy
NEW IN PREVENTIVE STRATEGIES—ROLE OF BIOMARKERS IN DIABETIC NEPHROPATHY
Novel Biomarkers
CHAPTER 5:
Pathophysiology of Diabetic Nephropathy
INTRODUCTION
POLYOL PATHWAY
Step 1
Step 2
HEXOSAMINE PATHWAY
Step 1
Step 2
ADVANCED GLYCATION END PRODUCTS
Advanced Glycation End Products/Receptors of Advanced Glycation End Products Interaction
ACTIVATION OF PROTEIN KINASE C
Protein Kinase C
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEMS AND DIABETIC NEPHROPATHY
ENDOTHELIAL DYSFUNCTION IN DIABETIC NEPHROPATHY
Role of Endothelial Nitric Oxide
Oxidative Stress as a Common Initiator
The Inflammatory Molecules in the Pathogenesis of Diabetic Nephropathy
Renal Cellular Infiltration and Interactions (Macrophages, T Cells and Neutrophils)
PODOCYTE PATHOPHYSIOLOGY IN DIABETIC NEPHROPATHY
TRANSFORMING GROWTH FACTOR BETA: IS IT THE COMMON DOWNSTREAM MEDIATOR OF DIABETIC NEPHROPATHY?
PATHOLOGY OF KIDNEY DISEASE IN DIABETES MELLITUS
DIABETIC NEPHROPATHY—PATHOLOGIC CLASSIFICATION
CHAPTER 6:
Microalbuminuria in Diabetic Nephropathy—A Marker or a Risk Factor?
MICROALBUMINURIA—WHAT IS IT?
THE INCIDENCE AND COURSE IN DIABETIC NEPHROPATHY
LIMITATIONS OF MICROALBUMINURIA
SCREENING
TECHNIQUES OF MEASURING
HOW TO TREAT MICROALBUMINURIA?
Hypertension and Renin-angiotensin-aldosterone Blockade
Antiproteinuric Antihypertensive
Hyperglycemia Control—Its Effect on Microalbuminuria
Four Year Follow-up of DCCT Patients: EDIC Phase 1
Seven to Eight Year Follow-up of DCCT Patients: EDIC Phase 2
Steno-2 Study and UK Prospective Diabetes Study
UK Prospective Diabetes Study
Other Studies
CHAPTER 7:
Diabetic Nephropathy—Treatment: Hyperglycemia Control
INTRODUCTION
GLYCEMIC CONTROL
The Course of Overt/Clinical Diabetic Nephropathy
Importance of Glycemic Control
Glycemic Control and Glomerular Filtration Rate
Glycemic Control Targets
Treatment of Glycemia—Drugs
Stages of Chronic Kidney Disease
Oral Hypoglycemic Agents
Sulfonylureas
Meglitinides
Dose Adjustments for Insulin Secretagogues
Metformin
Alpha-glucosidase Inhibitors
Thiazolidinediones
Dose Adjustments for insulin Sensitizers
Glucagon-like Peptide 1 (Incretin) Mimetics
Sitagliptin
Vildagliptin
Saxagliptin
Linagliptin
Dose Adjustment for Newer Agents
INSULIN AND INSULIN ANALOGS
Insulin Metabolism—Role of Kidney
Practical Insulin Usage
Basal-bolus Insulin
Type 1 Diabetes in Stages 3– 5 Chronic Kidney Disease
Insulin in Type 2 Diabetes with Nephropathy
Role of Kidneys in Controlling Hyperglycemia and The Dawn of the Sodium Glucose Co-transporter Inhibitors
The Renal Glucostat
Sodium Glucose Co-transporter Inhibitors 59
Weight Loss
CONCLUSION
CHAPTER 8:
Diabetic Nephropathy— Treatment: Hypertension and Proteinuria Therapy
INTRODUCTION
RECOMMENDATION ON TARGET BLOOD PRESSURE
HYPERTENSION THERAPY
Angiotensin Converting Enzyme Inhibitors/Angiotensin Ii Receptor Blockers as First-line of Therapy
THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN DIABETIC NEPHROPATHY
Evidence for the Role of Angiotensin Converting Enzyme Inhibitors in Preventing Progression of Diabetic Kidney Disease
Some Angiotensin Converting Enzyme Inhibitors Studies and Outcomes
Captopril
Enalapril
Lisinopril
Ramipril
Perindopril
Angiotensin II Receptor Blockers in Renoprotection in Diabetic Kidney Disease
Efficacy of Different Angiotensin II Receptor Blockers in various Studies
Losartan
Valsartan
Irbesartan
Candesartan
Telmisartan
Olmesartan
Role of Other Antihypertensives in Diabetic Nephropathy
Diuretics
Beta Blockers
Metoprolol
Bisoprolol
Carvedilol
Nebivolol
Calcium Channel Blockers
Algorithm for Hypertension Therapy in Diabetes
Additional Renin-Angiotensin-Aldosterone System Blockade: Is It Beneficial?
Angiotensin Converting Enzyme Inhibitors + Angiotensin receptor blocker—Dual Renin-Angiotensin-Aldosterone System Blockade
Aldosterone Antagonism + Angiotensin Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers
Direct Renin Inhibition
Trials with Supranormal Dose of Angiotensin II Receptor Blockers
SUMMARY
CHAPTER 9:
Diabetic Nephropathy—Other Therapies for Improving Renal Outcome
INTRODUCTION
PROTEIN RESTRICTION
SALT INTAKE
Salt Intake and Proteinuria
WEIGHT REDUCTION
LIPID MANAGEMENT AND STATIN THERAPY
ANEMIA IN DIABETES: ITS ROLE AND RELEVANCE IN DIABETIC KIDNEY DISEASE PROGRESSION
Incidence
Role of Hypoxia-inducible Factor
Factors other than Erythropoietin in the Causation of Anemia in Diabetes
Anemia and the Progression of Chronic Kidney Disease
Key Points
NEWER THERAPEUTIC APPROACHES
Advanced Glycation End Products: Their Role and Therapy
Protein Kinase C
Antifibrotic Agents
RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS AND THE PATHOGENESIS OF CHRONIC KIDNEY DISEASE
Key Points
ENDOTHELIN ANTAGONISM FOR DIABETIC NEPHROPATHY
ROLE OF ANGIOTENSIN-CONVERTING ENZYME AND DEGRADATION OF ANGIOTENSIN II
VITAMIN D IN DIABETIC NEPHROPATHY
ANTI-INFLAMMATORY THERAPY
A Novel Anti-inflammatory Drug—Bardoxolone
CHAPTER 10:
Diabetes and Kidney— Beyond Nephropathy
URINARY TRACT INFECTIONS
Bacteria
Viruses
Fungi
Tuberculosis
Key Points
PYELONEPHRITIS
Uncomplicated Pyelonephritis
Emphysematous Pyelonephritis
Renal Transplant Pyelonephritis
RENAL PAPILLARY NECROSIS
Clinical Presentation
Treatment
RENOVASCULAR DISEASE IN DIABETIC PATIENTS
Epidemiology of Atherosclerotic Renovascular Disease
Implications of the Presence of Atherosclerotic Renovascular Disease in Diabetic Patients: Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Antagonists Therapy
Detection of Atherosclerotic Renovascular Disease in Diabetes: Does it Really Matter? Renal Artery Stenosis: Anatomical Severity and Functional Significance
Conclusions
Key Points
DIABETIC AUTONOMIC NEUROPATHY
Bladder Dysfunction
Sexual Dysfunction
Male Sexual Dysfunction
Female Sexual Dysfunction
RENAL TUBULAR ACIDOSIS (TYPE-4 RTA)
CONTRAST NEPHROPATHY
KETOACIDOSIS AND KIDNEY
Pathophysiology
Diabetic Ketosis—Effects on Kidney: Fluid and Electrolytes
Kidney Function in Diabetic Ketosis
Acid-Base Changes
DEVELOPMENT OF RENAL DISEASE IN DIABETIC KETOSIS
CHAPTER 11:
Diabetic Nephropathy and Cardiovascular Morbidity
INTRODUCTION
PROTEINURIA GLOMERULAR FILTRATION RATE AND CARDIAC RISK
HYPERGLYCEMIA
OTHER RISK FACTORS
Role of Insulin Sensitizers
Role of Blood Pressure Control in Cardiovascular Disease Reduction
Role of Lipid Management
MAJOR MECHANISMS RESPONSIBLE FOR THE HIGH CARDIOVASCULAR DISEASE RISK IN DIABETIC NEPHROPATHY: SUMMARY
NON-TRADITIONAL RISK FACTORS
Homocysteine
Advanced Glycation Endproducts
Asymmetric Dimethylarginine
Anemia
THERAPEUTIC CONSIDERATIONS INCLUDING FUTURE TREATMENTS
SUMMARY
CHAPTER 12:
Diabetic End Stage Renal Disease—Is there Light at the End of the Tunnel?
INTRODUCTION
MANAGEMENT OPTIONS
BLOOD PRESSURE/SUGAR CONTROL IN DIABETIC END STAGE RENAL DISEASE
GLYCEMIC CONTROL
SPECIAL CONSIDERATION FOR HEMODIALYSIS IN DIABETES
Ischemic Heart Disease
Visual Impairment
Foot Ulcers
Neuropathic Problems
CONTINUOUS AMBULATORY PERITONEAL DIALYSIS
Use of Intraperitoneal Insulin in Continuous Ambulatory Peritoneal Dialysis
Peritonitis in Continuous Ambulatory Peritoneal Dialysis
Nutritional Issues in Continuous Ambulatory Peritoneal Dialysis
TRANSPLANTATION IN DIABETES
MANAGEMENT OF DIABETIC END STAGE RENAL DISEASE PATIENTS AFTER KIDNEY TRANSPLANTATION
New Onset Diabetes after Kidney Transplantation
PANCREAS AND KIDNEY TRANSPLANTATION
MANAGEMENT OF FAILING GRAFT AND RETRANSPLANTATION IN DIABETIC PATIENTS
INDEX
TOC
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