Diabetes and Kidney Disease (eBook)

Title page 5
Copyright page 6
Contents 7
Contributors 9
Preface 12
Part I: Introduction and Pathophysiology 13
Chapter 1: History of diabetic nephropathy: a personal account 15
Introduction 15
References 23
Chapter 2: Epidemiology of chronic kidney disease in diabetes 26
Introduction 26
Epidemiological measures and pitfalls 26
Chronic kidney disease without end-stage renal disease 28
Incidence of chronic kidney disease in individuals with diabetes 28
Prevalence of chronic kidney disease in individuals with diabetes 29
Renal replacement therapy 32
Incidence of renal replacement therapy in diabetes 36
Prevalence of renal replacement therapy in diabetes 37
Summary and perspectives 37
References 38
Chapter 3: Genetic risk factors for diabetic nephropathy 41
Genetic risk for diabetic nephropathy in a clinical context 41
Challenges in genetic research on diabetic nephropathy 43
What is diabetic nephropathy? 43
What is the optimal study design? 44
Methods for genetic analyses 45
Results of genetic analyses 47
Family-based linkage analyses 47
Genome-wide association studies 48
The future of genetic analyses 49
Translation into animal models 50
Translation into clinical use 50
Glossary 50
References 51
Chapter 4: Pathophysiology of diabetic nephropathy 57
Structural hallmarks of diabetic nephropathy 57
Hemodynamic changes and the role of different renal cell types in DN 58
Important mediators in DN 62
Advanced glycation end products 62
Transforming growth factor-?1 62
Connective tissue growth factor 64
Angiotensin II 64
Platelet-derived growth factor 64
Hepatocyte growth factor and bone morphogenic protein-7 64
Insulin-like growth factor-I 65
Vascular endothelial growth factor 65
Nitric oxide 65
Tubulointerstitial fibrosis, EMT, and EndMT in diabetic nephropathy 66
Hypoxia, oxidative stress and inflammation and DN 66
Hypoxia 66
Oxidative stress 68
Inflammation 68
Mouse models of DN 68
Streptozotocin model 68
db/db mouse model 69
Endothelial nitric oxide synthase-deficient mice 69
BTBR ob/ob mice 69
References 69
Chapter 5: Histology of human diabetic nephropathy 74
Clinical and epidemiologic aspects of diabetic nephropathy 74
Morphology and pathogenesis of characteristic histologic alterations of the kidney in diabetic nephropathy 76
Differential diagnoses of diabetic nephropathy 78
Concurrent renal findings in diabetes mellitus 79
Clinical perspective 79
References 79
Chapter 6: Natural history and diagnosis of diabetic kidney disease 82
Introduction 82
Course of disease 83
Type 1 diabetes and kidney disease 83
Type 2 diabetes and kidney disease 84
Remission/reversal of proteinuria 84
Tubuloglomerular feedback and early renal pathology 85
Current criteria for diagnosis 85
Risk factors 85
Guidelines for diagnosis 85
Future insights 88
References 89
Part II: Special Situations, Risk Factors and Complications 95
Chapter 7: Cardiovascular disease in diabetic nephropathy: pathophysiology and treatment 97
Introduction 97
Pathophysiology of atherothrombotic vascular disease 99
Pathophysiological conditions of vascular disease in diabetic nephropathy 100
Endothelial dysfunction 100
Insulin resistance 100
Hyperglycemia/hypoglycemia 100
Dyslipidemia 101
Platelet function 101
Advanced glycation end products 101
Asymmetric dimethylarginine 102
C-reactive protein 102
Homocysteine 103
Renin–angiotensin system/hypertension 103
Vascular calcification 103
Clinical evidence, prevention, and treatment strategies 104
Aspirin use 104
Lipid lowering 105
Antihypertensive treatment 105
Management of diabetes in the face of vascular disease 105
The challenge of nephropathy 107
Different clinical situations 107
Coronary artery disease 107
Cerebrovascular disease 108
Peripheral arterial disease 108
Microvascular complications 109
References 109
Chapter 8: Statin therapy in patients with diabetic nephropathy 113
Introduction 113
Macrovascular risk and atherogenic dyslipidemia 114
Diabetic microvascular risk 114
Intervention studies reducing microvascular outcomes in diabetic nephropathy 115
Multifactorial interventions 115
Other therapeutic approaches to reducing vascular risk in diabetic patients 116
Statins in later stages of diabetes and CKD and in patients on renal replacement therapy 117
Die Deutsche Diabetes Dialyse Studie 118
AURORA 118
SHARP 120
ALERT 120
What do the guidelines say? 121
Possible rationale of guideline statements 121
Special considerations 122
Perspectives 122
References 122
Chapter 9: Diabetes mellitus, bone and kidney 128
Diabetes and osteoporosis 128
Introduction 128
Osteoporosis in type 1 and type 2 diabetes 129
Falls and fracture risk 130
Proposed mechanisms underlying the increased fracture risk in diabetes 130
Specific influence of diabetes drugs on fracture risk 131
Cross-talk between bone remodeling and energy metabolism 132
Kidney and bone: renal osteodystrophy 132
Epidemiology 132
Pathophysiology 133
Diagnostic procedures: bone turnover markers, bone mineral density, bone biopsy 133
Classification of renal osteodystrophy by bone biopsy 135
Therapeutic options 135
References 136
Chapter 10: Diabetes, pregnancy and the kidney 141
Introduction 141
Historical perspective 142
Health aims 142
Physiological adaptations in normal pregnancy 142
Prevalence and diagnosis of diabetic nephropathy in pregnant women 142
Effect of pregnancy on diabetic nephropathy 143
Effect of diabetic nephropathy on the course of pregnancy 144
Counseling women with nephropathy while planning a pregnancy 145
Management of women with diabetic nephropathy during pregnancy 146
Medical nutritional therapy 146
Insulin 147
Arterial hypertension 147
Dyslipidemia, smoking 147
Exercise 148
Acute diabetes-specific complications 148
Pre-eclampsia 148
Diagnostic criteria of pre-eclampsia 149
Future perspectives 150
References 150
Chapter 11: Diabetic nephropathy in children 155
Introduction 155
Prevalence of diabetic nephropathy in children and adolescents 156
Risk factors 157
Nephrological differential diagnoses 157
Practical approach in patient care 158
Diagnostics 158
Therapy 160
References 162
Chapter 12: Diabetes, the kidney and retinopathy 165
Introduction 165
Retinal pathology 166
Epidemiology of diabetic retinopathy 167
Role of diabetic retinopathy in prediction of cardiovascular morbidity and mortality 169
Pathogenesis of diabetic retinopathy 170
Secondary effects 173
Links to diabetic nephropathy 173
Clinical treatment 174
References 176
Part III: Prevention and Therapy 181
Chapter 13: Reducing progression of diabetic nephropathy by antihyperglycemic treatment 183
Introduction 183
Diabetes control and development of nephropathy (primary prevention) 184
Practical consequences 186
Diabetes control and progression of diabetic nephropathy (secondary prevention) 187
Practical consequences 189
Diabetes control and survival prognosis with terminal renal insufficiency 189
Practical consequences 191
Monitoring of metabolic control 191
Blood glucose self-monitoring 191
Interfering substances 191
Changes in hematocrit 191
Continuous glucose monitoring 192
Long-term control 192
HbA1c 192
Fructosamine 193
Glycosylated albumin 193
References 194
Chapter 14: Dosage of antihyperglycemic drugs in patients with renal insufficiency 198
Introduction 198
Metformin 199
History 199
Mechanism of action 199
Indications and contraindications 199
Chronic kidney disease 200
Side effects 200
Evaluation 200
The metformin controversy in moderate to severe chronic kidney disease 201
Sulfonylureas 201
History 201
Mechanism of action 201
Indications and contraindications 202
Chronic kidney disease 202
Side effects 202
Evaluation 202
The controversy about myocardial infarction 202
Meglitinides 202
History 202
Mechanism of action 203
Indications and contraindications 203
Chronic kidney disease 203
Side effects 203
Evaluation 203
Thiazolidinediones 203
History 203
Mechanism of action 203
Indications and contraindications 203
Chronic kidney disease 204
Side effects 204
Evaluation 204
Glucosidase inhibitors 204
History 204
Mechanism of action 204
Indications and contraindications 204
Chronic kidney disease 204
Side effects 204
Evaluation 205
Incretin-based therapy 205
History 205
Mechanism of action 205
Indications and contraindications 205
Side effects 205
Renal insufficiency 206
Evaluation 206
Insulin 206
History 206
Mechanism of action 206
Indications and contraindications 206
Side effects 206
Renal insufficiency 206
Evaluation 209
References 209
Chapter 15: Reducing progression of diabetic nephropathy by antihypertensive treatment 214
Introduction 214
Prevention of diabetic nephropathy by blood pressure control 215
BENEDICT and ROADMAP 215
ABCD trial 216
DIRECT 217
Slowing progression of established diabetic nephropathy by antihypertensives 218
Type 1 diabetics 218
Type 2 diabetics with advanced diabetic nephropathy 218
Albuminuria and antihypertensive treatment 219
IRMA-2, MARVAL and DETAIL 219
ADVANCE 220
Renin-inhibition and RAS blocker combinations 220
ONTARGET 220
AVOID and ALTITUDE 221
Target blood pressure levels in patients with diabetic nephropathy 222
References 224
Chapter 16: Treatment of the patient with end-stage diabetic nephropathy 227
Anemia in the patient with end-stage diabetic nephropathy 227
Pathogenesis of anemia in diabetic CKD patients 228
Erythropoietin deficiency and hyporesponsiveness 228
Iron deficiency 228
Anemia of chronic disease 228
Decreased survival of red blood cells 228
Miscellaneous factors contributing to anemia 228
Consequences of anemia 228
Recommendations for anemia treatment 229
Target Hb level 229
Iron therapy 229
Adverse effects of anemia therapy 229
Bone and mineral metabolism disorders in diabetic patients with ESRD 231
Pathogenesis of BMD in diabetes and CKD 231
Treatment of BMD in diabetic patients with CKD 231
Glycemic control in diabetic patients with ESRD 232
Glycemia in the diabetic end-stage renal disease patient 232
Diagnostic tools of glycemic control in ESRD 232
Hypoglycemic agents in ESRD 233
Impact of glycemic control on outcomes 233
Hypertension in diabetic patients with end-stage renal disease 234
Assessment of hypertension in ESRD patients 234
Mechanisms of hypertension in ESRD patients 234
Management of hypertension in ESRD patients 235
Dyslipidemia in diabetic patients with ESRD 235
Therapy of dyslipidemia in diabetic ESRD patients 235
Cardiovascular disease in diabetic patients with ESRD 236
Cardiovascular risk factors 236
Evaluation of cardiovascular disease in ESRD 236
Aspirin use in ESRD 236
Management of acute coronary syndromes (ACS) in ESRD 237
Coronary artery bypass graft (CABG) surgery in ESRD 237
Comparing renal replacement therapies in diabetic patients with ESRD 237
Hemodialysis versus peritoneal dialysis 238
Potential benefits of PD in diabetes 239
Potential disadvantages of PD in diabetes 239
Where does the use of PD stand in diabetic patients? 239
References 239
Chapter 17: Combined pancreas and kidney transplantation or kidney alone transplantation for patients with diabetic nephropathy 244
Rationale of pancreas kidney transplantation for patients with diabetic nephropathy 244
Indications and contraindications to pancreas kidney transplantation 245
Evaluation of candidates for pancreas kidney transplantation 245
Cardiovascular, cerebrovascular, and peripheral vascular evaluation 246
Immunologic evaluation 248
Transplantation surgery 248
Evaluation of pancreas kidney donor 248
Kidney alone transplant surgery 254
Pancreas transplant surgery 255
Perioperative management 256
Pre- and postoperative management of pancreas kidney transplantation 256
Complications after pancreas kidney transplantation 257
Results of pancreas kidney transplantation 260
References 261
Index 265
Supplemental Images 283