Chronic kidney disease Flashcards
Vitamin D activation
1) diet
2) activated in liver to calcidiol
3) converted in kidney to calcitriol
FGF-23
expressed in osteocytes
acts on FGF receptors with co-factor Klotho - tissue expression of Klotho determines tissue specificity of FGF-23
main site of action: kidneys
increase phosphate excretion
inhibits kidney activation of calcidiol –> triol
PTH effects
bone: increase calcium (need calcitriol) and phosphate resorption
kidney: increase Ca resorption, increase phosphate excretion increase calcitriol activation
Intestine: indirect effect through increased calcitriol
Calcitriol effects
Bone: increase calcium and phosphate resorption
Kidney: increase ca and phos resorption
intestine: increase Ca and phos absorption
FGF-23 effects
increase phosphate excretion
reduce calcitriol activation
intestine: indirect effect through reduced calcitriol activation
Modulators of PTH
stim: reduced serum Ca, increased serum phosphate
inhib: increased serum Ca and calcitriol
Modulators of Calcitriol
stim: increased PTH, reduced serum phosphate
inhib: increased FGF-23, increased serum phosphate
FGF-23 modulators
increased calcitriol, increased phosphate load
Consequences of hyperparathyroidism
increase calcitriol –> more intestinal absorption of PO4
increase PO4 resorption at bone
increase PO4 excretion at kidney (PTH effect on excretion overrides inhibition by calcitriol)
net effect = hypophosphatemia
CKD effect on minerals
hyper-PTHism
hypocalcemia
hyperphosphatemia
low calcitriol
increased PTH resistance to calcemic effect
- high Ca no longer able to suppress PTH release
- Ca set point changed, need higher level of Ca to suppress PTH release
Diffusion modulators
responsible for most solute clearance
1) concentration gradient
2) molecular weight of solute
3) resistance of membrane
Convection - dialysis
ultrafiltration
1) water pushed/pulled through membrane
- hydrostatic ultrafiltration: based on transmembrane pressure
- ultrafiltration coefficient (KUf): amount of fluid transferred across membrane/hr/mmHg gradient
- osmotic ultrafiltration: water diffuses down its concentration gradient - will drag solutes wiht it (transient)
2) solvent drag: solutes that pass easily through membrane are dragged along with water
loss of total mass of solutes but not change in plasma concentration
Clearance
volume plasma cleared of indicator per unit time K = Cu x Q / Cb Cu = concentration in urine Cb = concentration in blood Q = urine flow
Phosphate binders
dietary first - difficult
1) Ca-based: tums, first line, reduce in hypercalcemia
2) Sevelamer, Lanthanum, Magnesium (non-calcium): alternative when hypercalcemic, use when concern over adynamic bone disease, metastatic/vascular calcification
3) Al-based binders: only short courses, not first line (Al toxicity)
Ca supplementation
Ca-based binders
Calcitriol supplementation:useful when phosphate is controlled, avoid if PTH is suppressed
need to avoid hypercalcemia - prefer low-normal Ca
Hormonal replacements for CKD
Ergocalciferol - early CKD, treat vit D deficiency
Calcitriol - when evidence of elevated PTH, avoid with hypercalcemia/phosphatemia, reduce dose when PTH is within target range
Calcimimetics
increase ca-sensing receptors in PT gland
useful when treatment limited by hypercalcemia, hyperphosphatemia
useful for refractory hyper-PTH in patients on dialysis
expensive
Hemodialysis
bloodflow & dialysate flow opposite
blood flow rate almost linear relationship w/ clearance
Net clearance = diffusive + convective transport
Hemodialysis -pros
quick
relieve uremia
works for most blood vessels
Hemodialysis - cons
4-8 h, 3x/wk meds, diets, fluid restriction need needle access travel sepsis, hypotension