Chronic Kidney Disease - Bone and Mineral Disease Flashcards
Dr. Covert
What change in minerals stimulates the Parathyroid Gland?
-Hypocalcemia: low Ca
-Hyperphosphatemia: high phosphorus
-> produces more Parathyroid hormone (PTH)
What are the effects of parathyroid hormones (PTH)?
-increase Ca absorption in the small intestine (since PTH was stimulated by Hypocalcemia)
-Bone breakdown releases Ca into the system: activates Osteoclasts, reactive Osteoblasts
-in the kidney: reduce Phos reabsorption (since PTH was activated by high Phosphorus), increase Ca reabsorption (since Ca is low), Vitamin D activation (inactive Vitamin D converted into active Vitamin D -> active Vitamin D works in the small intestine to increase Ca absorption)
How does the bone activate the parathyroid cell cycle?
- High calcitriol (activated Vitamin D)
- High phosphorus
–> The bones secrets FGF-23 to activate the parathyroid gland
-> Kidney: Vitamin D activation (more calcitriol), more Ca reabsorption -> They bind to the parathyroid gland and cause deactivation of the PTH cycle - NEGATIVE FEEDBACK
What are the effects on the PTH cycle in CKD patients?
the kidney should lower Phosphorus -> it cant -> Hypophosphatemic
the kidney should increase Ca -> it can’t -> ???
the kidney should activate Vitamin D -> it cant -> low in Vitamin D
Consequences of activation of PTH cycle in CKD patients
Stimulation of the PTH cycle without turning it OFF
-FGF-23 receptors are less sensitive
-Calcitriol receptors are less sensitive
-Calcium receptors are less sensitive
Diseases caused by Hyperparathyroidism
-too much Stimulation of Osteoclasts
Osteopenia (low bone density)
Osteoporosis -> risk for fracture
-Hypercalcemia/Hyperphosphatemia
Ca and Phosphours tend to bind together and clump in the blood -> Calciphylaxis
Symptoms of Calciphylaxis
-Calcific uremic arteriolopathy (CUA)
-Microvascular calcification: Ischemia, Infarction, Infection
-common in CKD patients
Drug target to correct the PTH cycle
-lower phosphorus
-resensitize the Ca receptors (turn OFF signal)
-using Vitamin D analogs (early CKD patients)
Phosphate binders
-bind dietary Phosphate -> too lower phosphate to decrease the activating signal to the bone
-has to be taken with food
-Non-calcium-containing phosphate binders are preferred! bc we also want to lower Ca
-patients might only afford to buy the calcium-containing phosphate binder (like TUMS)
Non-calcium-containing Phosphate binder
-all are prescription-only
-Sevelamer (Renvela)
-Lanthanum (Fosrenol)
-AlOH (Amphojel) - most potent (caution eliminated by the kidney: Aluminia toxicity)
-Ferric citrate (auryxia) -contain iron
-Sucroferric oxyhydroxide (Velphoro) - contain iron
-> CKD patients might also suffer from anemia -> so extra benefit for these patients
Why are Non-calcium-contain Ph binders preferred?
because we want to prevent an increase in Ca
-it will desensitize the Ca receptor -> making it less effective in turning OFF the PTH cycle
Vitamin D analogues
Nutrintional form: not activated -> not preffered bc CKD patients can’t activate the Vitamin D preform
-Ergocalciferol, Cholecalciferol
Activated form:
Clictriol, Paricalcitol, Doxercalciferol
Why are Vitamin D analogs not preferred anymore?
because in the long-term active Vitamin D will increase the reabsorption of Calcium -> which will desensitize the Ca receptors
When are Vitamin D analogs considered?
In patients with early CKD and hypocalcemia
bc they can still convert inactive into active Vitamin D) and need more calcium
Calcimimetics
-Cinacalcet (Sensipar)
-increases the sensitivity of calcium-sensing receptors on the parathyroid gland
-> so it can recognize high levels of calcium to turn OFF the PTH cycle
net effect:
lower Ca, bc Ca reabsorption will be downregulated
lower PTH
