The Spectrum of Mineral and Bone Disorder in Chronic Kidney Disease

617 Pages·2010·6.855 MB·English

by  Klaus Olgaard, Justin Silver, Isidro B. Salusky

The Spectrum of Mineral and
Bone Disorders in Chronic
Kidney Disease
This page intentionally left blank
The Spectrum of
Mineral and Bone
Disorders in Chronic
Kidney Disease
SECOND EDITION
Edited by
Klaus Olgaard
Isidro B. Salusky
Justin Silver
1
1
Great Clarendon Street, Oxford ox2 6dp
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Contents
Contributors xv
List of Abbreviations xxi
Introduction xxv
1 Definition and classification of renal osteodystrophy and chronic
kidney disease–mineral bone disorder (CKD–MBD) 1
Sharon M. Moe
Renal osteodystrophy 3
Chronic kidney disease–mineral bone disorder 7
Conclusion 10
References 10
2 New aspects of normal bone biology 15
Susan M. Ott
Introduction 15
Osteoclasts 17
Osteoblasts 21
Osteocytes 25
Systemic hormones 26
Summary 28
References 28
3 Osteocytes and mineral metabolism 31
Susan C. Schiavi and Jian Q. Feng
Introduction 31
The osteoblast/osteocyte lineage 31
Osteocyte role in mineralization 32
Roles of osteocytes in the control of Pi homeostasis 36
Osteocytes’ role in phosphate dysregulation associated with CKD 39
The influence of CKD on osteocyte function 40
Summary 40
References 41
4 Calcium-sensing receptors (CaSR) in kidney, bone, and vessels 45
Ogo I. Egbuna and Edward M. Brown
Introduction 45
Expression, structure, and signaling of the extracellular CaSR 46
vi CONTENTS
CaSR in the kidney 49
CaSR and bone 51
The CaSR and blood vessels 53
Summary 56
References 57
5 Regulation of parathyroid hormone biosynthesis and gene
expression 61
Tally Naveh-Many and Justin Silver
Introduction 61
Regulation of PTH expression by 1,25(OH) vitamin D 61
2
Post-transcriptional regulation of P TH gene expression by calcium,
phosphate, and CKD 63
Fibroblast growth factor-23 and P TH gene expression 69
Conclusions 70
References 71
6 Abnormal parathyroid gland function in CKD 77
Ewa Lewin and Mariano Rodriguez
Introduction 77
Regulation of PTH gene transcription in CKD 77
Regulation of PTH release in CKD 78
Phosphate and abnormal PTH synthesis and secretion in CKD 87
Vitamin D and abnormal PTH synthesis and secretion in CKD 89
Abnormal PTH synthesis and secretion due to other factors 90
Post-transcriptional modulation of PTH synthesis in CKD 92
Changes in the intracellular and peripheral metabolism of
PTH in CKD 93
Hyperplasia of parathyroid glands in CKD 94
Parathyroid function and VDR polymorphisms 97
Control of increased parathyroid mass 97
Parathyroid tissue apoptosis and necrosis 100
Summary 101
References 101
7 PTHrP physiology and pathophysiology, and the
PTH/PTHrP receptor 109
David Goltzman
Introduction 109
Characteristics of the PTHrP gene 109
Regulation of PTHrP production 110
Processing and degradation of PTHrP 111
CONTENTS vii
Physiological actions of PTHrP 111
Mechanisms of action of PTHrP 114
PTH/PTHrP receptor expression in renal osteodystrophy 118
Summary 119
References 119
8 Vitamin D metabolism and action in CKD 125
Ishir Bhan, Kevin J. Martin, and Ravi Thadhani
Introduction 125
25-Hydroxyvitamin D deficiency in CKD 125
Calcitriol production in CKD 126
The vitamin D receptor 128
Effects of declining 1,25-dihydroxyvitamin D on mineral
metabolism 128
Non-traditional actions of vitamin D 129
Cardiac effects of calcitriol 129
Vitamin D and the immune system 130
Additional effects of vitamin D 131
Vitamin D and survival in CKD 131
Summary 132
References 132
9 Growth factors and cytokines in renal bone disease 137
Esther A. González and Kevin J. Martin
Introduction 137
The cells of bone 137
Bone remodeling 139
Effects of uremia on skeletal biology 141
References 143
10 Bone histomorphometry in renal osteodystrophy 145
Arnold J. Felsenfeld and Armando Torres
Historical perspective of renal osteodystrophy 145
Pathology of different forms of renal osteodystrophy 146
TMV classification by KDIGO 156
Measurement of PTH and indications for bone biopsy 157
The spectrum of renal osteodystrophy 161
Osteitis fibrosa and mixed disease 164
Osteomalacia 164
Adynamic bone 166
Conclusions 168
References 168
viii CONTENTS
11 Biochemical markers of bone metabolism in CKD 173
Pablo Ureña, Klaus Olgaard, and Kevin J. Martin
Introduction 173
Calcium 174
Phosphate 177
Parathyroid hormone 178
Circulating markers of bone formation 181
Circulating markers of bone resorption 188
C-terminal cross-link telopeptides 189
Bone sialoprotein 192
Galactosyl hydroxylysine 192
Summary 193
References 193
12 Imaging of the skeleton and the joints in CKD 199
Yaakov H. Applbaum
Introduction 199
Renal osteodystrophy 199
Joint complications 210
Other skeletal complications 212
Summary 215
References 216
13 Non-invasive assessment of vascular calcification and arterial
stiffness 217
Paolo Raggi and Gérard M. London
Introduction 217
Plane roentgenography 218
Ultrasonography 219
Echocardiography 220
Computed tomography techniques 222
Measurement of arterial stiffness 226
Clinical relevance of arterial stiffness in chronic kidney disease 230
Conclusions 230
References 231
14 Osteopenia in uremia 235
Ezequiel Bellorin-Font, Judith Adams, and John Cunningham
Introduction 235
Definition of osteoporosis and osteopenia 235
Diagnosis of osteoporosis and bone densitometry 236
Other bone densitometry techniques 239
Other research methods 240
CONTENTS ix
Definition of osteoporosis and osteopenia in CKD 241
Prevalence and risk factors of osteoporosis and fractures in uremic
patients 242
Pathogenesis and bone histology of osteoporosis in uremic
patients 243
Treatment and prevention of osteoporosis and fractures in uremic
patients 244
Specific therapies 246
Conclusions 248
References 248
15 Acidosis and renal bone disease 253
David A. Bushinsky
Clinical relevance 253
Acute acidosis 254
Chronic acidosis 256
Overview of the response of bone to acid 261
References 262
16 Dialysis-associated amyloidosis 267
T. Bardin
Pathophysiology 267
Epidemiology 268
Clinical features of dialysis-associated amyloidosis 269
Amyloid arthropathy 270
Destructive arthropathies 271
Pathological fractures of bone 274
Management of amyloid carpal tunnel syndrome and arthropathy
in dialysis patients 276
References 278
17 Pathogenesis of vascular calcification: experimental studies 283
Rukshana C. Shroff and Catherine M. Shanahan
Introduction 283
Calcification occurs at distinct sites in CKD patients 284
Vascular smooth muscle cell phenotypic change in response
to injury 284
Physiological versus pathological calcification: similarities between bone
ossification and ectopic calcification— in vivo evidence 286
Model systems to study vascular calcification 288
The role of mineral imbalance in ectopic calcification—clinical and
experimental studies 290
Summary 298
References 300