3. Introduction
• CKD-MBD describes:
• Abnormal changes in calcium, phosphate, parathyroid hormone (PTH) and
vitamin D metabolism
• the various forms of bone disease that may develop alone or in combination
in CKD
• the vascular consequences that accompany it
• This expanded focus has been driven by observational studies
suggesting that CKD-MBD (and its treatment) may impact on
cardiovascular morbidity and mortality
• Renal osteodystrophy is reserved to describe the bone pathologies
associated with CKD
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4. KDIGO definition of CKD-MBD and renal
osteodystrophy
Definition of CKD-MBD
A systemic disorder of mineral and bone metabolism due to CKD, manifested by either one or a combination
of the following:
• Abnormalities of calcium, phosphate, PTH or vitamin D metabolism
• Abnormalities of bone turnover, mineralization, volume, linear growth or strength
• Vascular or other soft tissue calcification
Definition of renal osteodystrophy
• Renal osteodystrophy is an alteration of bone morphology in patients with CKD
• It is one measure of the skeletal component of the systemic disorder
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5. Epidemiology
• In a study done in India in patients with CKD, the prevalence of
hypocalcemia, hyperphosphatemia, hyperparathyroidism and
hypovitaminosis D was 64.2%, 81.1%, 49.5% and 89.5% respectively
• In the same study cardiac valvular calcification was seen in 22.1% of
patients who had echocardiography, mostly involving the mitral valve
• In Enugu, the prevalence of CKD-MBD in pre-dialysis patients were 70%
hyperphosphatemia, 85% hyperparathyroidism and 100% low levels of
25(OH) D
• In a study done among CKD patients on hemodialysis in AKTH, it was found
that 58% had CKD-MBD, 39.5% hyperphosphatemia, 46% hypocalcemia,
31% HPTBD and 27% ABD and none of the patient had normal 25(OH) D
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6. Pathophysiology
• With normal renal function, concentrations of PO4 and Ca2+ are
maintained through interaction between PTH, 1,25(OH)2D (calcitriol),
fibroblast growth factor-23 (FGF-23)
• And their principal targets i.e. bone, kidney, the GI tract, and
parathyroid glands
• However, in the setting of CKD with GFR below 60ml/min/1.73m2
(stage 3-5D CKD), there is decreased urinary phosphate excretion
with resultant hyperphosphatemia
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7. Pathophysiology
• In CKD 3-5D, there is also decreasing renal mass and synthetic
function
• Phosphate accumulation
• Increased production of fibroblast growth factor 23 (FGF-23) and
other phosphotonins in response to phosphate accumulation
• FGF-23 increases urinary PO4 excretion, potently suppress 1alpha
hydroxylase, leading to decreased production of 1,25(OH)2D
• Decreased klotho expression, leading to further increased levels of
FGF-23
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8. Pathophysiology
• Decreased level of 1,25(OH)2D leads to decreased absorption and
reabsorption of calcium from the gut and kidneys respectively
• This leads to hypocalcemia and its effects on the parathyroid glands
• The decreased level of 1,25(OH)2D stimulates parathyroid glands
• The hyperphosphatemia, hypocalcemia, increased level of FGF-23,
decreased 1,25(OH)2D stimulates the parathyroid glands resulting in
increased parathyroid hormone secretion, leading to secondary
hyperparathyroidism
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9. Pathophysiology
• Longstanding secondary hyperparathyroidism ultimately leads to
hyperplasia of the glands with autonomous or tertiary
hyperparathyroidism
• Secondary hyperparathyroidism enhances urinary phosphate
excretion, and raise serum calcium level
• Secondary hyperparathyroidism leads to hyperparathyroid bone
disease (High turn over disease) characterized by increased
osteoclastic activity, cyst formation and bone marrow fibrosis (osteitis
fibrosa cystica)
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10. Pathophysiology
• Adynamic bone disease describes a state in which both bone
formation and resorption are depressed and the skeleton becomes
inert
• Bone turnover is reduced, usually where there is over-treatment
withactive vitamin D, low PTH (after surgical
parathyroidectomy), accumulation of aluminium used as a
phosphate binder
• There may be hypercalcemia, particularly if calcium intake is high
(excess calcium cannot be laid down in bone); the serum alkaline
phosphatase is normal and the PTH is low
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11. Pathophysiology
• Deficiency of 1,25-(OH)2 D and hypocalcaemia can also result in
impaired mineralization of osteoid, thus osteomalacia
• Osteoporosis is commonly found in CKD, often after
transplantation and the use of corticosteroids
• Longstanding hyperparathyroidism causes increased bone density
(osteosclerosis), seen particularly in the spine, where alternating
bands of sclerotic and porotic bone give rise to a characteristic
‘rugger jersey’ appearance on lateral X-ray
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12. Pathophysiology
• Vascular calcification
• Appears intimately linked to the aberrant mineral and bone
metabolism of CKD as well as to its treatment
• May explain the association between increased PO4, CaxP and PTH,
and adverse cardiovascular events
• The arterial calcification maybe intimal or medial (monckeberg
calcinosis)
• In addition, cardiac valvular and other soft tissue calcification is a
frequent finding in advanced CKD
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16. Secondary hyperparathyroidism/hyperparathyroid
bone disease/osteitis fibrosa cystica
• Usually asymptomatic
• Clinical sequelae occur late, including bone pain, arthralgia, and muscle
weakness
• Pruritus due to cutaneous calcium phosphate deposition
• Bony deformity e.g. resorption of terminal phalanges
• Increased fracture risk
• Brown tumour
• Marrow fibrosis contributes to anemia and poor ESA response
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18. Adynamic bone disease
• Usually asymptomatic
• Adynamic bone buffers calcium poorly; increased Ca2+ is common,
particularly if oral calcium intake is significant
• Increased risk of soft tissue and vascular calcification
• Aluminium-related low turnover bone disease is often painful, with an
increased risk of spontaneous fracture
• Tumoral calcinosis
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19. Osteomalacia
• This refers to a defect in mineralization
• Uncommon as an isolated finding
• Generally related to a deficiency of 1,25(OH)2 D, but aluminium
intoxication and acidosis are also important risk factors
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20. Hyperparathyroid bone
disease
Adynamic bone disease Osteomalacia
Calcium Variable Often increased Normal or increased
phosphate Increased ++ Normal or increased + Normal or increased +
PTH High Low or normal Usually low or normal
ALP Raised Normal Normal
Bone biopsy findings Increased osteoblast &
osteoclast activity, fibrosis
Decreased osteoblast &
osteoclast activity, thin
osteoid
Decreased osteoblast &
osteoclast, widened
osteoid
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21. Calciphylaxis
• Calciphylaxis also known as calcific uremic arteriolopathy, this
is a rare but serious life-threatening complication in CKD patients
• It presents as painful skin patches, plaques and ulcers, with non-
healing eschars panniculitis and dermal necrosis
• Mortality in patients with calciphylaxis is almost always due to sepsis
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23. KDIGO recommendations for frequency of
biochemical testing in CKD
CKD stage calcium phosphate PTH ALP calcidiol
3 Every 6-
12months
Every 6-
12months
Baseline Baseline Baseline
4 Every 3-6months Every 3-6months Every 6-
12months
Every 6-
12months
Baseline
5 and 5D Every 1-3months Every 1-3months Every 3-6months Every 3-6months Baseline
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24. Treatment
• Goals of treatment:
• Keep serum Ca2+ and PO4 within the normal range
• Keep bone turnover and strength as near normal as possible
• Keep serum PTH appropriate to these objectives
• Prevent the development of parathyroid hyperplasia
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25. Treatment
• Measures to decrease serum PO4 :
• Dietary PO4 restriction
• meat, eggs, milk, cola, beer, yoghurt
• Oral phosphate binders (prevent absorption)
• Taken with meal
• Calcium based phosphate binders
• Aluminium based phosphate binders
• Non-calcium, non-Aluminium binders
• Removal through adequate dialysis
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26. Treatment
• Measures to suppress PTH synthesis and secretion:
• Calcitriol/vitamin D analogues (e.g. alfacalcidol, paricalcitol, doxercalciferol)
• Calcimimetic agents
• Small molecules that bind to the parathyroid CaR and mimic the effect of increased
extracellular Ca2+
• Type I e.g. calcium
• Type II e.g. cinacalcet
• Measures to normalize serum Ca2+:
• Appropriate calcium intake ± supplementation (including calcium-containing
binders)
• Appropriate vitamin D treatment
• Appropriate dialysate concentration
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27. Treatment
• Parathyroidectomy
• indication
• Partial or total
• Pre-operative considerations
• Isotopic scanning
• Laryngoscopy
• Prevention of hungry bone syndrome
• Post operative considerations
• Hemorrhage
• Hypocalcemia
• Radiological ablation
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28. NKF-KDOQI therapeutic targets
CKD stage GFR(ml/min) PTH (pg/mL) Calcium
(mmol/L)
Phosphate(m
mol/L)
3 30-59 35-70 Normal 0.87-1.48
4 15-29 70-110 Normal 0.87-1.48
5 and 5D <15 or dialysis 150-300 2.1-2.37 1.13-1.78
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29. Conclusion
• CKD-MBD is invariably present beyond stage 3 CKD, and its
management represents a significant clinical challenge with no single
therapeutic intervention that fits all, hence customized management
to individual patients is necessary
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30. References
• Larry J et al. Harrison’s Principle of Internal Medicine. 20th edition
2018:2115-7
• Kumar P, Clark M. Clinical Medicine. 9th edition 2017:1953-59
• Simon S et al. Oxford Handbook of Nephrology and Hypertension. 2nd
edition 2014:232-48
• Brian W et al. Davidson’s Principles and Practice of Medicine. 22nd edition
2014: 486-88
• Alhaji Abdu et al. Prevalence and Pattern of CKD-MBD among hemodialysis
patients in Kano. Annals of African Medicine. 2019;18(4): 191-5
• JU Okoye et al. Prevalence of CKD-MBD in pre-dialysis patients using
biochemical markers in Enugu.African Journals Online. 2015;15(3)
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