mineral bone disease Flashcards
What are the mechanisms that potentiate hyperparathyroidism in CKD?
- Phosphate retention
- Hypocalcemia
- Decreased production of 1,25-dihydroxyvitaminD3 -> also leads to hypocalcemia
Monitoring parameters for CKD-MBD
Calcium and Phosphorous, iPTH, and 25-OH Vitamin D
Corrected calcium equation
measured calcium + 0.8(4 - albumin)
CKD Stage 3 Monitoring Parameters
Calcium and Phos: Q6-12 months
iPTH: Q12 months
25-OH Vitamin D: at baseline
CKD Stage 4 Monitoring Parameters
Calcium and Phos: Q3-6 months
iPTH: Q3-12 months
CKD Stage 5 Monitoring Parameters
Calcium and Phos: Q1-3 months
iPTH: Q3-6 months
what are some consequences of CKD-MBD?
- CV Disease
- Bone Disease
- Calciphylaxis (CUA)
CUA = calcific uremic arteriolopathy ~ extravascular calcification
types of renal osteodystrophy (2)
- adynamic bone osteomalacia
- ostetis fibrosa
adynamic bone osteomalacia vs. ostetis fibrosa
adynamic bone osteomalacia = over-treated hyperparathyroidism -> low bone turnover
ostetis fibrosa = under-treated hyperparathyroidism -> high bone turnover
goals of treatment of CKD-MBD (4)
- prevent consequences of cardiovascular and extravascular calcification
- prevent the development of secondary hyperparathyroidism and renal osteodystrophy
- maintain critical biochemical parameters (Ca, Phos, and iPTH) within target ranges
- Prevent mortality (NONE decrease mortality)
General Approach to Pharmacologic Treatment of CKD-MBD
First line: Phosphate binders
Second line: Activated Vitamin D (or calcimimetic)
Third line: Calcimimetic (or activated vitamin D - whichever one you didn’t choose for 2)
how do phosphate binders help treat CKD-MBD?
they help prevent the initial pathologic mechanism of phosphate retention by binding phosphate in the diet and preventing absorption!
Phosphate Pyramid
Dark sodas (lots of phosphate)
Egg white, fruits and veggies, protein-free products (less phosphate)
If corrected calcium is LOW, what phosphate binder do you use…?
Calcium based binder:
Less Ca2+ More $ = Calcium acetate (PhosLo)
More Ca2+ Less $ = Calcium carbonate
Calcium based binder effects
increases serum Ca2+ and decreases serum phosphate concentration
Calcium acetate
Calcium based phosphate binder
PhosLo
25% elemental Ca2+
Less Ca2+ and More $
Rx only
2x phosphate binding capacity vs. carbonate
Calcium carbonate
Calcium based phosphate binder
40% elemental Ca2+
-> MORE risk of hypercalcemia
More Ca2+ and Less $
OTC
*requires acidic pH for phosphate binding
If corrected calcium is NORMAL-HIGH, what phosphate binder do you use…?
Non-Calcium based binder
First line: Sevelamer
Lanthanum carbonate (chewable)
Ferric citrate (iron deficiency anemia)
Sucroferric oxyhydroxide (lowers pill burden)
Sevelamer dosing
based on serum phospahte (higher = more drug)
5.5-7.5 mg/dL: 800 mg PO TID
7.5-9 mg/dL: 1200-1600 mg PO TID
> 9 mg/dL: 1600 mg PO TID
Sevelamer
Non-calcium based phosphate binder
Renvela
1st line!
also helps to decrease LDL and increase HDL
Sevelamer DDIs
take other meds 1 hour before or 3 hours after taking sevelamer
adverse effects of Sevelamer
Gi upset, DIARRHEA
Lanthanum carbonate
Non-calcium based phosphate binder
Fosrenol
Chewable!
counseling point for Lanthanum carbonate
tablet MUST be chewed
adverse effects of Lanthanum carbonate
GI upset, lanthanum accumulation
Lanthanum carbonate DDIs
take other meds 1 hour before and 3 hours after taking Lanthanum carbonate (not as many DDIs as Sevelamer)
Ferric citrate
Non-calcium based phosphate binder
Auryxia
IDA -> iron supplement AND phosphate binder
dosing of Ferric citrate
420 mg ferric iron 92 tabs) PO TID
adverse effects of Ferric citrate
GI, diarrhea, iron overload, stool discoloration
Sucroferric oxyhydroxide
Non-calcium based phosphate binder
Velphoro
lowers pill burden
VERY potent phosphate binder and ALSO CHEWABLE
dosing of sucroferric oxyhydroxide
500 mg iron PO TID MUST be chewed
adverse effects of sucroferric oxyhydroxide
GI upset, diarrhea
what is an advantage of sucroferric oxyhydroxide?
lower pill burden
(non-inferior to sevelamer carbonate)
if corrected serum calcium AFTER phosphate binding is at a stable dose is NORMAL-LOW…
activated vitamin D and analogs
endogenous:
calcitriol (rocaltrol)
less increase in Ca/PO4:
paricalcitol
doxercalciferol (hectorol)
(less hypercalcemia and hyperphosphatemia)
if corrected serum calcium AFTER phosphate binding is at a stable dose is NORMAL-HIGH…
Calcimimetic (dec. serum Ca)
PO: cinacalcet (sensipar)
IV: etelcalcitide (parsabiv)
KDIGO 2017 Guidelines for serum calcium, serum phosphate, and iPTH
goal serum calcium: avoid hypercalcemia; asymptomatic hypocalcemia is ok
goal serum phosphate: towards the normal range (3.5-5.5 mg/dL)
goal iPTH: 2-9x ULN (~ 150-600 pg/mL)
Phosphorous Balance and Hemodialysis
to achieve neutral phosphate balance, binders must remove 257 mg/day
most important counseling point for phospahte binders?
TAKE WITH FOOD!
what are some adverse effects of calcium based phosphate binders?
- abdominal discomfort, nephrolithiasis
- “Stones, Bones, and Abdominal Groans”
- Calciphylaxis - systemic calcification
Calcium Based Phosphate Binders DDIs
Fluroquinolones
Levothyroxine (Synthroid)
Iron
separate administration ~ 2 hours
Non-Calcium Based Phosphate Binders
First line: Sevelamer carbonate
*HCl not used due to worsening metabolic acidosis
Second line: Lanthanum carbonate (Fosrenol)
Third line: Aluminum hydroxide (Amphojel)
what is a disadvantage of Sevelamer and Lanthanum carbonate?
they are both expensive!
Aluminum based binders
LAST LINE
aluminum hydroxide (amphojel)
very effective phosphate binding
adverse effects of aluminum hydroxide
GI upset, CNS toxicity (dialysis encephalopathy), microcytic anemia
risk of aluminuk toxicity
-> inc. serum aluminum leads to aluminum deposition and toxicity (osteomalacia, microcytic anemia, neurologic sequelae) also ESA resistance
Goals of therapy for Phosphate Binders
Corrected calcium: 8.5-10.2 mg/dL (avoid hypercalcemia; asymptomatic hypocalcemia is ok)
Normal serum phosphorous towards the normal range: 2.7-4.6 mg/dL (or 3.5-5.5 for some)
Clinical Pearls for Phosphate Binders
- adherence is critical
- counsel to TAKE WITH FOOD
- combo of calcium AND non-calcium binders can be used
when should vitamin D/calcitriol be used in a CKD-MBD patient?
- elevated iPTH despite calcium and phosphate at goal
- persistent hypocalcemia with hyperparathyroidism
when should vitamin D/calcitriol NOT be used in a CKD-MBD patient?
hypercalcemia and/or hyperphosphatemia
(use calcimimetics and optimize phosphate binders first!!!)
what is the target therapy with vitamin D/calcitriol agents in ESRD?
iPTH maintained 2-9x ULN (~150-600 pg/mL)
prevent hypercalcemia
what is recommended in CKD and ESRD if vitamin D deficiency?
serum 25-hydroxycholecalciferol < 30 ng/mL
ergocalciferol (vitamin D2)
cholecalciferol (vitamin D3)
inactive forms of Vitamin D
ergocalciferol and cholecalciferol
vitamin D2 and D3
- poor conversion to active form (calciferol) in ESRD
- available OTC
- inexpensive
calcifediol (rayaldee)
prohormone of active form of vitamin D
approved for CKD stages 3 and 4 (NOT ESKD; no dialysis or CKD 5)
initiation requirements for calcifediol
serum calcium must be < 9.8 mg/mL and phosphorous </= 5.5 mg/dL
side effects of calcifediol
hypercalcemia and hyperphosphatemia
cinacalcet MOA
calcimimetic -> sensitizes parathyroid gland
adverse effects of cinacalcet
GI - N/V very common
hypocalcemia - paresthesias, myalgia, cramping, tetany
monitor Ca for 1 week then monthly
QT prolongation (due to hypocalcemia)
etelcalcetide (parsabiv)
IV calcimimetic dosed at HD
less GI side effects
hypocalcemia
QT prolongation
General Treatment Algorithm
Treat to targets of:
- towards normal phosphate range
- avoiding hypercalcemia; asymptomatic hypocalcemia is ok
USE CORRECTED CALCIUM!!
- iPTH ~ 150-600 pg/mL
Start with Phosphate Binders
- initial choice based on serum calcium (CORRECTED)
Add active Vitamin D or calcimimetic based on trends of Ca, Phos, and iPTH
- active vitamin D if Ca LOW, Phos at target, iPTH HIGH
- calcimimetic if Ca HIGH, Phos at target, iPTH HIGH
