IPC Kidney: CKD Mineral Bone Disorder (Week 3)

mineral bone disease is a result of...

secondary hyperparathyroidism (increased PTH)

what are the 2 primary stimuli of PTH release in CKD?

phosphate retention (primary elim in kidneys), decreased 1,25-OH vitamin D (calcitrol)

calcium sensing proteins in the ___ sense serum calcium levels

parathyroid glands

in response to slight declines in serum calcium, the parathyroid glands secrete ___. this stimulates the activity of ___ enzyme in the kidney, resulting in increased production of ___.

PTH, 1-hydroxylase, calcitrol

___ activates the vitamin-D dependent transport system in the ___, increasing the absorption of dietary ___ and ___.

calcitrol, small intestine, calcium phosphorus

___ and ___ act on the skeleton to increase the ___ of calcium and phosphate into circulation.

calcitrol, PTH, mobilization

in the kidneys, calcitrol and PTH increase...

calcium reabsorption and phosphorus excretion

in CKD, secondary hyperparathyroidism develops due to... resulting in...

phosphate retention and reduced renal production of active vitamin D, hyperphosphatemia and hypocalcemia

in CKD secondary hyperparathyroidism, the resulting hyperphosphatemia inhibits the ___, so that production of active ___ by the kidney is reduced.

1-alpha-hydroxylase, 1,25 dihydroxy vitamin D3

in CKD secondary hyperparathyroidism, the ___ is the most important factor regulating PTH secretion

serum ionized calcium

in CKD secondary hyperparathyroidism,the effects of calcium on parathyroid cells are mediated by....

a membrane bound calcium sensing receptor

in CKD secondary hyperparathyroidism, calcimimetic agents such as ___ increase the sensitivity of the CaR to ___, thereby ....

calcitrol, extracellular calcium, inhibiting the release of PTH and lowering PTH levels within a few hours of administration

in CKD secondary hyperparathyroidism, ___ modulates ___ production by binding to the cytoplasmic vitamin D receptor

vitamin D, PTH

what is the clinical presentation of CKD-MBD?

usually asymptomatic, identified through routine lab testing

consequences of CKD-MBD may be seen in...

more severe or uncontrolled disease

what is the corrected calcium formula?

measured calcium + 0.8(4-albumin)

for CKD stage 3: how often should calcium/phospphorus, iPTH, and 25-OH vitamin D be monitored for CKD-MBD?

every 6-12 months, every 12 months, at baseline

for CKD stage 4: how often should calcium/phospphorus, iPTH, and 25-OH vitamin D be monitored for CKD-MBD?

every 3-6 months, every 3-12 months, -

for CKD stage 5: how often should calcium/phospphorus, iPTH, and 25-OH vitamin D be monitored for CKD-MBD?

every 1-3 months, every 3-6 months, -

for CKD-MBD monitoring, ___ should be checked concurrent with calcium

albumin

bone-specific alkaline phosphatase reflects...

biosynthetic activity of osteoblasts (bone formation)

what are the 3 consequences of CKD-MBD?

CV disease, bone disease, calciphylaxis (CUA-- calcific uremic arteriolopathy ~ extravascular calcification)

what are the consequences of secondary hyperparathyroidism?

ESA resistance, left ventricular hypertrophy, parathyroid hyperplasia, myocardial fibrosis, immune dysfunction, lipid metabolism (hypertriglyceridemia), renal osteodystrophy

what are the 3 types of renal osteodystrophy, that can occur as a consequence of secondary hyperparathyroidism?

ostetitis fibrosa, adynamic bone disease, osteomalacia

what are the goals of treatment for CKD-MBD?

1. prevent consequences of CV and extravascular calcification

2. prevent the development of secondary hyperparathyroidism and renal osteodystrophy

3. maintain critical biochemical properties within target ranges (calcium, phosphate, iPTH)

4. prevent mortality

what is the general approach to pharmacologic tx of CKD-MBD?

1st control serum phosphorus, 2nd control iPTH (either activated vitamin D or calcimimeric or combo)

for CKD-MBD, if serum calcium is normal-high use a ___ binder

non-calcium based phosphate

for CKD-MBD, if serum calcium is low use a ___ binder

calcium based phosphate

for CKD-MBD, what is the 1st line non-calcium based phosphate binder?

sevelamer carbonate

for CKD-MBD, which non-calcium based phosphate binder is chewable?

lanthanum carbonate

for CKD-MBD, which non-calcium based phosphate binder is used for IDA?

ferric citrate

for CKD-MBD, which non-calcium based phosphate binder increases pill burden?

sucroferric oxyhydroxide

for CKD-MBD, what are the 4 non-calcium based phosphate binders?

sevelamer carbonate, lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide

for CKD-MBD, what are the 2 calcium based phosphate binders?

calcium acetate, calcium carbonate

for CKD-MBD, which calcium based phosphate binder has less calcium but costs more money?

calcium acetate

for CKD-MBD, which calcium based phosphate binder is less expensive but has more calcium?

calcium carbonate

what is the brand name of tenapanor?

xphozah

what is the indication of tenapanor?

add on therapy to lower serum phosphorus in dialysis-dependent CKD, in pts with inadequate response to phosphate binders OR pts intolerant of phosphate binders

what are contraindications of tenapanor?

mechanical GI obstruction, age < 6 years old

what is the dose of tenapanor?

30mg PO BID before morning/evening meals

what is the major drug interaction with tenapanor?

sodium polystyrene sulfonate, separate admin by 3 hours

for CKD-MBD, if serum calcium is normal to high use ___ to lower PTH

calcimimetic

for CKD-MBD, if serum calcium is normal to low use ___ to lower PTH

activated vitamin D and analogs

which calcimimetic is PO?

cincalcet

which calcimimetic is IV?

etelcalcetide

which activated vitamin D is endogenous?

calcitrol

which activated vitamin D/analogs have less increase in calcium and phosporus?

paricalcitol, doxercalciferol

what is the brand name of sevelamer carbonate?

renvela

what is the brand name of lanthanum carbonate?

fosrenol

what is the brand name of ferric citrate?

auryxia

what is the brand name of sucroferric oxyhydroxide?

velphoro

what is the brand name of calcium acetate?

phoslo

what is the brand name of cinacalcet?

sensipar

what is the brand name of etelcalcitide?

parsabiv

what is the brand name of calcitrol?

rocaltrol

what is the brand name of paricalcitrol?

zemplar

what is the brand name of doxercalciferol?

hectorol

for secondary hyperparathyroidism, goals of therapy are indicated for CKD stages ___

3-5D

what is the corrected calcium goal for secondary hyperparathyroidism in CKD 3-5D?

serum calcium 8.5-10.2 mg/dL, avoid hypercalcemia

what is the phosphorus goal for secondary hyperparathyroidism in CKD 3-5D?

towards the normal range 2.7-4.6 mg/dL OR 3.5-5.5 per older KDOQI guidelines

what is the ca x phos goal for secondary hyperparathyroidism in CKD 3-5D?

<55 (not recommended to use ca x phos per updated guidelines)

what is the iPTH goal for secondary hyperparathyroidism in CKD 3-5D?

<2-9x the upper limit for normal assay, 150-600 pg/ml

when gfr ___, use of phosphate binders with dietary restrictions is necessary

30 ml/min

what is the MOA of phosphate binders?

limit phosphate absorption in GI tract by binding with dietary phosphate

what is the number 1 counseling point for phosphate binders?

administer with meals to maximize effect

limit elemental calcium from phosphate binders intake to ___

<1500 mg/day

prior to initiation of phosphate binders, must assess ___ and ___

calcium, phosphate (hypercalcemia = non-calcium based)

for calcium based phosphate binders, avoid calcium ___ and ___ salts

citrate, chloride (ONLY use acetate or carbonate)

what are some ADRs of calcium based phosphate binders?

abdominal discomfort, nephrolithiasis, calciphylaxis

what is calciphylaxis? what drug class is it associated with?

systemic calcification occurs in coronary arteries/skin/organs, calcium based phosphate binders

calciphylaxis from calcium based phosphate binders is at highest risk if...

ca x phos > 55

what is the dosing of calcium carbonate?

1250 mg PO TID with meals

what is the dosing of calcium acetate?

1334 mg PO TID with meals

1250mg of calcium carbonate = ____mg elemental Ca

500

1334mg of calcium acetate = ___mg elemental Ca

334

calcium carbonate vs acetate: which is OTC, which is Rx?

carbonate: OTC, acetate: Rx

calcium carbonate vs acetate: not all forms meet USP dissolution and disintegration requirements

carbonate

calcium carbonate vs acetate: liquid formulation available (phoslyra)

acetate

calcium carbonate vs acetate: requires acidic pH for phosphate binding

carbonate

calcium carbonate vs acetate: 2x more phosphate binding capacity

acetate

which drugs interact with calcium based phosphate binders? what happens?

fluoroquinolones, levothyroxine (synthroid), iron, prevents absorption

how far apart should you administer calcium based phosphate binders and fluoroquinolones/levothyroxine/iron?

~2 hours

sevelamer carbonate has limited impact on ___, may improve ___

acid/base balance, metabolic acidosis

sevelamer HCL is generally ___ and worsens ___

not used, metabolic acidosis

which non-calcium based phosphate binder is second-line? third-line?

lanthanum carbonate, aluminum hydroxide

aluminum hydroxide is good for ___ since it is ___. it is NOT good for ___ use bc it can cause...

acute, potent, chronic, dementia/worsen osteomalacia

if serum phosphate is 5.5-7.5 mg/dL, what is the dose of sevelamer?

800mg PO TID

if serum phosphate is 7.5-9 mg/dL, what is the dose of sevelamer?

1600mg PO TID

if serum phosphate is >9 mg/dL, what is the dose of sevelamer?

1600mg PO TID

what are some ADRs of sevelamer?

gi upset, diarrhea, feeling full, loss of appetite

other drugs should be taken ____ before or ___ after sevelamer due to...

1 hour, 3 hours, gelatinous film it leaves in the gut

sevelamer also ___ LDL and ___ HDL

decreases, increses

besides tablet, what is the other dosage form of sevelamer available?

powder for oral suspension

what is the initial dose of lanthanum carbonate?

500mg PO TID

what is an important counseling point for lanthanum carbonate?

MUST be chewed

what are some ADRs of lanthanum carbonate?

gi upset, lanthanum accumulation (relatively benign)

other medication should be taken ___ before and ___ after lanthanum carbonate

1 hour, 3 hours

which has more DDIs: sevelamer or lanthanum?

sevelamer

which phosphate binders are iron based?

ferric citrate, sucroferric oxyhydroxide

what is the dose for ferric citrate?

420mg PO TID