Management of Diabetic Nephropathy

Book Cover......Page 1
Half-Title......Page 2
Title......Page 3
Copyright......Page 4
Contents......Page 6
Contributors......Page 8
Preface......Page 15
1 Introduction......Page 16
REFERENCES......Page 18
I The pathogenesis and clinical description of diabetic nephropathy......Page 20
CLASSIFICATION......Page 21
DIAGNOSIS......Page 22
GEOGRAPHY......Page 23
SEX AND AGE......Page 25
FAMILIAL AGGREGATION......Page 26
ENVIRONMENTAL RISK FACTORS......Page 27
STAGES IN DEVELOPMENT OF TYPE 2 DIABETES......Page 29
COMPLICATIONS......Page 31
REFERENCES......Page 34
INTRODUCTION......Page 41
Histology......Page 42
Islet autoantibodies......Page 43
Preclinical diabetes......Page 44
Latent autoimmune diabetes in adults......Page 45
Association with the HLA locus......Page 46
Associations with non-HLA loci......Page 47
Gender......Page 48
Worldwide increase in frequency......Page 49
Migration studies......Page 50
Viral infection......Page 52
Seasonality......Page 53
REFERENCES......Page 54
DEFINITION OF DIABETIC NEPHROPATHY (DN)......Page 59
NATURAL HISTORY OF DN......Page 61
STAGES OF DN......Page 62
HYPERFILTRATION AND DN......Page 63
CONCEPT OF MICROALBUMINURIA......Page 65
CHOICE OF SCREENING MODALITY FOR ALBUMINURIA......Page 66
PREDICTIVE VALUE OF AER BELOW THE MICROALBUMINURIC RANGE......Page 67
MACROALBUMINURIA AND CARDIOVASCULAR DISEASE......Page 69
SECULAR TRENDS IN DN......Page 71
PROGRESSION PROMOTERS OF DN......Page 72
THE RELATIONSHIP OF BLOOD PRESSURE TO DN......Page 73
DYSLIPIDAEMIA AND DN......Page 76
ASSOCIATION OF RETINOPATHY WITH NEPHROPATHY......Page 77
ETHNIC AND RACIAL DIFFERENCES IN THE INCIDENCE OF DIABETIC RENAL DISEASE......Page 78
REFERENCES......Page 81
BACKGROUND......Page 90
FAMILIAL AGGREGATION OF DIABETIC NEPHROPATHY......Page 91
ETHNIC VARIABILITY IN DIABETIC NEPHROPATHY......Page 92
THE ROLE OF GENDER......Page 93
THE ROLE OF GENETIC HYPERTENSION......Page 94
LIPIDS AND DIABETIC NEPHROPATHY......Page 95
THE RENIN-ANGIOTENSIN SYSTEM (RAS) AND DIABETIC NEPHROPATHY......Page 96
SODIUM/HYDROGEN EXCHANGER (NHE) ACTIVITY AND NEPHROPATHY......Page 98
RENAL STRUCTURAL PARAMETERS AS RISK FACTORS FOR DIABETIC NEPHROPATHY......Page 99
PROGRESSION OF MICROALBUMINURIA......Page 100
CONCLUSIONS......Page 101
REFERENCES......Page 102
Advanced glycation end-products (AGEs)......Page 108
Evidence for a role of AGEs in diabetic kidney disease......Page 109
Inhibitors of AGE formation......Page 110
RAGE blockers......Page 111
Evidence for a role of the AR/polyol pathway in diabetic kidney disease......Page 112
Diacylglycerol (DAG)-protein kinase C (PKC) pathway......Page 113
PKC inhibitors......Page 114
Growth hormone (GH) and insulin-like growth factors (IGFs)......Page 115
Evidence for a role of GH/IGFs in diabetic kidney disease......Page 116
AGE inhibition......Page 117
Evidence for a role of TGF-β in diabetic kidney disease......Page 118
PKCβ inhibition......Page 119
Neutralizing antibodies......Page 120
Angiotensin/renin-angiotensin-system......Page 121
Evidence for a role of RAS in diabetic kidney disease......Page 122
Evidence for a role of endothelin in diabetic kidney disease......Page 123
ET antagonists......Page 124
CONCLUSIONS AND OUTLOOK......Page 125
REFERENCES......Page 126
II Therapeutic measures in patients with diabetic nephropathy......Page 139
EFFECT OF IMPROVED GLYCAEMIC CONTROL ON HYPERFILTRATION AND RENAL ENLARGEMENT......Page 140
Can improved glycaemic control retard progression from microalbuminuria to overt diabetic nephropathy?......Page 141
CAN IMPROVED GLYCAEMIC CONTROL AFFECT THE DECLINE IN GFR?......Page 143
EFFECT OF GLYCAEMIC CONTROL ON STRUCTURAL KIDNEY DAMAGE......Page 144
SUMMARY......Page 145
REFERENCES......Page 146
INTRODUCTION......Page 149
Target values of blood pressure......Page 151
Cost-effectiveness......Page 153
Clinical considerations......Page 154
Twenty-four-hour ambulatory blood-pressure monitoring (ABPM)......Page 155
Weight maintenance......Page 156
Vegetarian diet......Page 157
DRUG THERAPY......Page 158
Dose-response regulation......Page 159
Mechanism of action......Page 161
Efficacy and dosage......Page 162
Angiotensin-converting enzyme inhibitors (ACE inhibitors)......Page 163
Mode of action......Page 164
Control of blood pressure......Page 165
Side effects......Page 166
Potency and dose......Page 167
Renal effects......Page 169
Clinical considerations......Page 170
Mode of action......Page 171
Beta-blockers in diabetic nephropathy......Page 172
Use in diabetic nephropathy......Page 173
ACE inhibitors......Page 174
The debate: CCBs in comparison with ACE inhibitors......Page 175
REFERENCES......Page 176
NORMAL DIETARY PROTEIN INTAKE......Page 182
GRADES OF EVIDENCE......Page 183
RESULTS......Page 184
DISCUSSION......Page 185
REFERENCES......Page 187
PROPOSED MECHANISMS OF LIPID-ENHANCED RENAL INJURY......Page 190
Type 1 diabetes......Page 191
Experimental models......Page 192
Clinical studies......Page 193
DIABETES, HYPERLIPIDAEMIA AND MACROVASCULAR DISEASE......Page 194
REFERENCES......Page 196
INTRODUCTION......Page 199
CORONARY HEART DISEASE (CHD)......Page 200
Pathophysiology of CHD......Page 201
Lifestyle modification......Page 203
Medical management of cardiac risk factors......Page 204
SECONDARY PREVENTION OF CVD......Page 205
ST segment elevation infarction (STEMI)......Page 206
Revascularization of a diabetic patient......Page 207
Pathophysiology of diabetic cardiomyopathy......Page 208
Left-ventricular diastolic dysfunction and diastolic heart failure......Page 210
Silent myocardial ischemia......Page 211
Cardiac autonomic neuropathy (CAN)......Page 212
REFERENCES......Page 214
INTRODUCTION......Page 225
Hyporeninaemic hypoaldosteronism......Page 226
Sodium......Page 228
Magnesium......Page 229
METABOLIC ACIDOSIS......Page 230
Metformin......Page 231
Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists......Page 232
Cyclo-oxygenase (COX) inhibitors......Page 233
WATER HOMEOSTASIS AND DIABETES MELLITUS......Page 234
Potassium......Page 235
REFERENCES......Page 236
AGE formation......Page 244
Strategies for blocking AGE formation......Page 245
PKC isoenzymes......Page 246
Effects of PKC activation......Page 247
Dual vasopeptidase inhibitors in development......Page 248
CONCLUSIONS......Page 249
REFERENCES......Page 250
DIAGNOSIS OF DIABETIC NEPHROPATHY......Page 253
Primary prevention of microalbuminuria......Page 254
Primary prevention of microalbuminuria......Page 255
Reducing the rate of decline in renal function......Page 256
Multidisciplinary approach......Page 257
REFERENCES......Page 259
INTRODUCTION......Page 261
HYPERTENSION......Page 262
DIETARY PROTEIN RESTRICTION......Page 263
CARDIOVASCULAR DISEASE......Page 264
RENAL OSTEODYSTROPHY......Page 265
CHOICE OF MEDICATIONS AND ADJUSTMENT OF DOSAGES......Page 266
REFERENCES......Page 267
PREGNANCY ALTERATIONS IN RENAL FUNCTION AND GLUCOSE HOMEOSTASIS......Page 273
Nephropathy: renal disease outcome......Page 274
Nephropathy: maternal and fetal outcome......Page 276
Macrovascular disease—Coronary artery disease......Page 277
Control of blood pressure......Page 278
CONCLUSION......Page 279
REFERENCES......Page 280
16 The use of dialysis in the treatment of diabetic patients with end-stage renal disease......Page 283
OPTIONS FOR RENAL REPLACEMENT THERAPY......Page 284
PREPARATION OF THE DIABETIC PATIENT FOR RENAL REPLACEMENT THERAPY......Page 285
TIMING TO INITIATE RENAL REPLACEMENT THERAPY......Page 286
MAINTENANCE HEMODIALYSIS......Page 287
Intradialytic hypotension......Page 288
Malnutrition......Page 289
Peritonitis......Page 290
Metabolic abnormalities......Page 291
REFERENCES......Page 292
ASSOCIATION OF DIABETIC RETINOPATHY AND DIABETIC NEPHROPATHY......Page 297
Hyperglycemia and quality of metabolic control......Page 298
Proteinuria and nephropathy......Page 299
RENAL AND PANCREAS TRANSPLANTATION IN PATIENTS WITH DIABETIC RETINOPATHY......Page 300
Serous retinal detachment......Page 301
TREATMENT......Page 302
REFERENCES......Page 303
EPIDEMIOLOGY......Page 306
Neuropathy......Page 307
Foot deformity and Charcot’s arthropathy......Page 308
Arterial disease......Page 309
Infection......Page 310
Assessment of neuropathy......Page 312
Assessment of vascular disease......Page 314
Assessment of infection......Page 317
MANAGEMENT OF DIABETIC FOOT PROBLEMS AND PERIPHERAL VASCULAR DISEASE......Page 318
Peripheral vascular disease......Page 319
Infection......Page 320
REFERENCES......Page 323
NUTRITIONAL MANAGEMENT OF DIABETIC PATIENTS WITHOUT RENAL INVOLVEMENT......Page 327
Overweight (BMI 25–29.9) and obese patients (BMI >30)......Page 328
Physical exercise......Page 329
Stages of CKD (Table 19.3)......Page 330
Protein intake......Page 331
Energy requirements (Tables 19.4–19.7)......Page 332
Assessing nutritional status......Page 334
Nutritional support......Page 336
Electrolyte and water balance......Page 337
Potassium* and hyperkalaemia (Table 19.12). *K+ 1 mmol=39 mg K+......Page 338
Zinc......Page 340
REFERENCES......Page 341
Survival......Page 343
Cardiovascular disease......Page 344
Impact on secondary complications......Page 346
PANCREAS TRANSPLANTATION......Page 347
Survival: solitary pancreas grafts......Page 348
Urologic......Page 349
Metabolic......Page 350
Neuropathy......Page 351
Impact on cardiovascular disease......Page 352
CHOICE OF TRANSPLANTATION IN DIABETICS......Page 353
Technique of transplantation......Page 355
Barriers to success......Page 356
REFERENCES......Page 357
21 Summary of the therapeutic approach to the patient with diabetic nephropathy......Page 365
THE THERAPEUTIC APPROACH TO THE PATIENT WITH DIABETIC NEPHROPATHY......Page 366
Antihypertensive treatment (Chapter 7)......Page 368
Treatment of cardiac complications......Page 369
Summary of management of the patient with mild to moderate renal involvement (Chapter 13)......Page 370
The use of dialysis in the treatment of diabetic patients with end-stage renal disease (ESRD) (Chapter 16)......Page 371
FUTURE STRATEGIES FOR THE TREATMENT OF DIABETIC NEPHROPATHY (Chapter 12)......Page 372
Retinopathy......Page 373
REFERENCES......Page 374
Index......Page 376