CKD-Mineral Bone Disease Flashcards
CKD-MBD is a systemic disorder of bone metabolism from CKD manifesting as either one or combination of:
(3: biochemical, bone, extraskelatal)
- Biochemical laboratory abnormalities
- Ca, phos, PTH, Vit D - Bone disease (renal osteodystrophy)
- Abnormal bone turnover, mineralisation, volume, reduced strength, reduced linear growth - Calcification of extraskeletal tissues (vasculature and soft tissues)
Renal osteodystrophy is _____
Bone pathology is based on __ classification
Alteration of bone morphology in patient with CKD
TMV classification - turnover, mineralisation, volume
- Turnover: low / normal / high
- Mineralisation: normal / abnormal
- Volume: low / normal / high
Factors contributing to secondary hyperparathyroidism and high turnover bone diseases
- Hyperphosphataemia - diminished kidney excretion
- Hypocalcaemia
- Impaired kidney production of calcitriol (active 1,25 vit D)
- Alteration in control of PTH gene transcription
- Skeletal resistance to calcaemmic action of PTH
- Fibroblastic growth factor (FGF23)
__ is the high turnover bone lesion associated with moderate to severe __.
Clinical features (2)
PTH levels
Radiologic features
Histologic features
Osteitis fibrosa cystica - caused by hyperparathyroidism
Features: non-specific bone pain, proximal myopathy
PTH levels: elevated 350 - 500 pg/mL
Radiologic Features
1. Subperiosteal resorption
2. Brown tumour
2. Salt and pepper appearance of skull (mottled and granular)
Histologic Features
- Increased turnover: increased bone resorption and formation with increased osteoclasts and osteoblasts
- Abnormal mineralisation - increase of woven bone, marrow fibrosis, osteoid deposition
- Increased volume
Treatment of hyperparathyroidism and CKD-MBD
A. Phosphorous control
1. Dietary restriction (1g protein = 10-12mg phosphate)
2. Phosphate binders taken immediate before/during/after meals
A. Calcium-based phosphate binders: calcium carbonate and calcium acetate*
B. Non-calcium based: sevelamer, lanthanum, sucroferric oxyhydroxide
3. Adequate dialysis
B. Prevention of hypocalcaemia
4. Oral calcium supplement
5. Correct vitamin D deficiency
6. Dialysis (added calcium)
C. Suppression of PTH production
7. Vitamin D receptor activators (activated Vit D - alfacalcidol, calcitriol)
8. Calcimimetics (cinacalcet, elecalcetide)
9. Surgical parathyroidectomy +/- deltoid implantation
Low turnover bone disease is also known as __ or __
- Low or absent bone formation (low osteoblast and osteoclast activity)
- Defect in mineralisation, endosteal fibrosis.
- Reduced osteoid formation
Causes of low turnover bone disease (6)
PTH levels are __ (range), with __ calcium
Adynamic bone disease, osteomalacia
Causes
1. Aluminum toxicity
2. Vitamin D deficiency
3. Hyperphosphataemia
4. Metabolic acidosis
5. Elevated cytokines (IL-1, TNF)
6. Low estrogen and testosterone levels
7. Uraemic toxins
PTH low (< 100-200 pg/mL), with high calcium (hypercalcaemia)
(Occasionally PTH mildly elevated ue to bone resistance to PTH)
Mixed bone disease is caused by: (4)
- Histologic description
Cause
1. Hyperparathyroidism
2. Aluminum toxicity
3. Uraemia
4. Unknown
Histology
1. Increased remodeling, resorption and osteoid formation
2. With areas of low bone formation
What are the expected biochemical changes of the different histological classifications of MBD?
What is calciphylaxis (calcific uraemic arteriolopathy)?
What are the incidence?
What are the major risk factors?
What is the prognosis?
Life threatening vasculopathy of skin and subcutaneous tissues
Systemic medial calcification of arterioles causing ischaemia and subcutaneous necrosis
Incidence
- Mostly occurs in ESRF (4% in dialysis, <1% CKD)
- But also rarely seen in patients with normal kidney function and calcium/phosphate metabolism
Risk Factors
1. Caucasian
2. Female
3. Comorbids: DM, obesity, CKD, liver disease
4. Malignancy
5. Hypercoagulable states - prot C/S def, APLS
6. Malnutrition
7. Hypercalcaemia, hyperphosphataemia
8. Medication: vit D analogues, calcium containing phosphate binders, steroids, warfarin, iron
9. Long term dialysis
Prognosis
High mortality: 1-year survival 45%, 5-year survival 35%
Most patients die from complicationso f woundi nfection
Hyperphosphataemia is an independent risk factor for: (3)
- Secondary hyperparathyroidism
- Renal osteodystrophy
- Vascular calcification
What are the difference in elemental calcium between available calcium salts?
Which calcium salt binds phosphate better?
What is the downside of using calcium based phosphate binder?
Elemental calcium percentage
Calcium gluconate - 9%
Calcium lactate - 13%
Calcium acetate - 25%
Calcium carbonate 40%
Calcium acetate binds to phosphate better than calcium carbonate or calcium lactate
Calcium based phosphate binders increase calcium level in the body, increase risk of calcification and calciphylaxis
Sevelamer is __ that bind phosphate through ion exchange. It also acts as __ and __.
Sevelamer hydrochloride formulation may cause __
It is able to bind phosphate __
Non-absorbable cationic polymer
Cholesterol binding resin, binds fat soluble vitamins
Metabolic acidosis
Phosphate binding: 80mg/g
Lanthanum carbonate is taken __ to bind dietary phosphate from being absorbed in __
It has profound side effect: (4)
With meal
Intestines
Side Effects:
1. Gastrointestinal upset
2. Myalgia and muscular cramps
3. Peripheral oedema
4. Accumulates in the bone
Sucroferric oxyhydroxide is an __ that binds with __ in __, and is eliminated __
Side effects: (2), occurs early treatment and resolves over time
Contraindications to sucroferric oxyhydroxide (5)
Iron based phosphate binder
Binds with phosphate in intestines
Eliminated in the faeces
Side effects
1. Diarrhoea
2. Discoloured faeces
Contraindications
1. Haemochromatosis
2. Other iron accumulation disorder
3. Recent peritonitis in last 2 months, or 3 episodes in a year
4. Gastro or hepatic disorder (ALT or AST > 3x ULN)
5. Major gastrointestinal surgery
Dialysis prescription modification to improve hyperphosphataemia
Peritoneal dialysis
1. High transporter: increase therapy volume, increase cycles
2. Others: longer dwells or increase PD duration
3. APD: add on day dwell, or mid-day exchange, or convert to CAPD
4. Increase convective clearance by increasing UF
Measure ratio of dialysate phosphate to plasma phosphate
- Ideal ratio: 0.6
Haemodialysis
1. Optimise vascular access and Qb
2. Check for recirculation
3. Use high flux dialyser
4. Increase frequency of sessions
5. Change to haemodiafiltration (HDF)
