CKD - MBD Flashcards
CKD - MBD - pathophysiology
1) kidney impairment
- reduce P excretion = hyperphosphatemia
- P bind to Ca so high P = low Ca = hypocalcaemia
- reduce production of 1-alpha-hydroxylase required to convert inactive to active Vit D = Vit D deficiency
- Vit D required for Ca absorption: Vit D deficiency = hypocalcaemia
2) hyperphosphatemia + hypocalcemia + Vit D deficiency = Secondary hyperparathyroidism (SHPT)
- stimulate parathyroid gland to secrete/produce PTH = bone disease/CVS problem
CKD - MBD - benefit of Vit D
increase P and Ca reabsorption
CKD - MBD - Vit D reference values
- adequate: > 30
- insufficient: 16-30
- mild deficiency: 5-15
- severe deficiency: < 5
CKD - MBD - Type of Vit D
1) Vit D2: Ergocalciferol
- require activation by liver/kidney
- plant sources
- additional methyl group, C double bond btwn C22 & C23
- lower bioactivity
- Rx-strength 50k IU
2) Vit D3: Cholecalciferol
- already active form
- form in skin from UV radiation, oily food (oily fish), UV radiation 7 (dehydrocholesterol fromlanoline)
- no bioactivity
- 200-1000 IU
3) fat soluble, X need daily supplement
CKD - MBD - Clinical consequences - bone disease
1) high bone turnover disease (High PTH)
- Osteitis Fibrosa Cystica
. higher osteoblast activity = increase bone formation & reabsorption = brittle bone/fracture
2) low bone turnover disease (low PTH)
- osteomalacia, adynamic bone disease
- overtreatment of SHPT
. decreased mineralisation cuz lesser Ca deposited
. higher extracellular Ca = vascular calcification
CKD - MBD - clinical consequences - presentation
1) renal osteodystrophy
2) Calcification
3) calciphylaxis
4) Coronary Uremic Arteriolopathy (CUA)
- prolonged uncontrolled SHPT, high P, Ca
- extraskeletal calcification, Ca deposited in artery = vascular thrombosis = ischaemia, skin necrosis/ulceration
5) vascular calcification
- metastatic calcification of extremities, soft tissue, coronary artery, myocardium, mithral/aortic valve
CKD - MBD - goals of therapy
1) maintain normal lvls of:
- Ca: 2.1-2.6 mmol/L (corrected if albumin < 40, corrected Ca = measured Ca + (0.02 + (40-albumin))
- P: 0.7 - 1.5 mmol/L
- PTH: G3/4/5 (1.6 - 7.2), G5D (2-9X ULN of essay)
2) prevent/reduce parathyroid gland hyperplasia
3) maintain normal skeletal function
4) prevent extraskeletal/vascular calficiation
5) reduce CVS morbidity & mortality
6) improve long term outcome
CKD - MBD - manage Hyperphosphatemia - Diet
- intake goal: 800-1000mg/day
- sources: beer/ale, chocolate drinks, dark cola, milk tea, milk, cheese, ice cream, carp, oyster, crayfish, organ meat, sardine (animal based more absorbed than plant based) nut, seed, caramel, oat/bran/wheat, dried bean, pea
CKD - MBD - manage Hyperphosphatemia - Phosphorus binder - Ca salt
. Ca salt
. combine w P to form insoluble calcium phosphate & excreted
. types of preparation
1) Ca carbonate
- 40% elemental Ca
- 500mg TDS w meals
- SE: hypercalcemia, C, N/V, loss appetite, urolithiasis
2) Ca Acetate
- 25% elemental Ca
- 1-2 tabs TDS w meals
- SE: hypercalcemia, C, N/V, loss of appetite
. limitations
- potential DI: bind w drugs, lower F
- potential hypercalcemia (monitor before initiate)
. advantages: cheap
CKD - MBD - manage Hyperphosphatemia - Phosphate binder - non Ca salt - Sevelamer
- non absorbable polymer (hydrogel) that inhibit phosphate absorption
- Sevelamer carbonate (Renvela) 800mg - 1600mg TDS w meals
- SE: C, D, N/V, flatulence, indigestion, metabolic acidosis
- advantages: no Ca/Al tox, lipid lowering effect, reduce mortality, pleotropic effect
- disadvantages: pill burden, large pill to swallow
CKD - MBD - manage Hyperphosphatemia - Phosphate binder - non Ca salt - Lanthanum
- patient w hypercalcemia & cannot tolerate Sevelamer/can’t swallow large tablet
- form high insoluble lanthanum P complex, inhibit dietary P absorption
- 500, 1000 mg chewable tablets TDS w meals
- SE: abdominal pain, D, V
CKD - MBD - manage Hyperphosphatemia - Phosphate binder - non Ca salt - Al based
- not first line, only for severe hyperphosphatemia > 2.2 mmol/L not controlled by other binders
- bind w phosphorus in gut
- Al hydroxide 600mg tablet/mixture
- SE: GI (C, D, GI obstruction), Phosphate depletion (weakness, mental status change), Al tox (dementia, encephalopathy, worsen anemia, osteomalacia, adynamic bone disease (esp concurrent citrate salt use), avoid long term use > 4 wk)
CKD - MBD - manage Hyperphosphatemia - Phosphate binder - non Ca salt- Sucroferric oxyhydroxide (Velphoro)
- 500mg TDS w meal, increase to 1g based on response
- contains elemental Fe but minimal Fe absorption
- as effective as Sevelamer but lower pill count
- SE: GI (N, V, black stool)
CKD - MBD - manage Hyperphosphatemia - non phosphate binder/diet
increase dialysis removal of P
CKD - MBD - manage Vit D deficiency - indication
- late stage CKD
- PTH persistently high/continue to rise
CKD - MBD - manage Vit D deficiency - other than calcitriol and alfacalcidol
. Caltrate+D: 600mg Ca, 400 unit Vit D3
. Lynae: 120mg Ca, 1000 unit Vit D3
. Cholecalciferol drops: 15k Vit D3/drop
CKD - MBD - manage Vit D deficiency - Calcitriol
- hydroxylated at 1, 25 position by kidney & liver respectively, fully active form of Vit D3
- MOA: non-selective increase GI absorption of Ca, suppress PTH secretion & synthesis
- dosage form: oral (pre-dialysis/PD), IV (HD)
- oral dosing regime: start 0.25mcg 3x/wk, titrate according to patient response
- IV dose: 1mcg 1-3x/wk
- limitation: increase GI absorption of Ca/P = hyperphosphatemia & hypercalcemia (dose-limiting SE)
- advantage: not affected by renal/hepatic impairment since already active
CKD - MBD - manage Vit D deficiency - Alfacalcidol
- hydroxylated at 1-alpha position by kidney), synthetic Vit D metabolite, need activation by 25-hydroxylase in liver
- PO/IV
- 1-4 mcg 3x/wk or daily
- limitation: high Ca/P, require hepatic func for conversion
CKD - MBD - manage hypercalcemia - calceium sensing receptor (CaSR)
- CaSR principal regulator of PTH secretion located on surface of chief cell in parathyroid gland that detect change in serum Ca
CKD - MBD - manage hypercalcemia - Cincalcet
- MOA: bind to and increase sensitivity of CaSR to extracellular Ca = reduce PTH & Ca conc
- initial 25mg PO daily, up titrate by 25mg every 3 wk, max 100mg daily
- SE: N/V, D, hypocalcemia (seizure, tetany, muscle cramp)
- monitor: Ca (drops during initiation, adjust/titrate: every wk, maintenance: every 2 wk), PTH (initiation/titrate 2x/month, stable 1x/month)
- DI: substrate of CYP, inhibit CYP2D6
CKD - MBD - manage hypercalcemia - Etelcalcetide (IV)
- MOA: bind to and activate CaSR = PTH reduction &? suppression
- initiate (HD): 2.5-5mg IV 2x/wk, titrate 2.5/5mg increment every 4 wk, max 15mg 3x/wk
- monitor Ca & PTH
- initiate etlcalcitide 7 day after last cinacalcet dose + ensure Ca normal range
- SE: N/V, D, hypocalcemia
- DI: none since no 1st pass
CKD - MBD - last line management
parathyroidectomy: surgical removal of parathyroid gland
