24 - CKD 3 Bone Disease Flashcards
Pathophysiology
CKD - Mineral & Bone Disease
w/ progressive CKD, imbalance occurs with:
PHOS / Calcium / VIT D
VV
Secondary HypoThyroidism
&
↑FGF-23 / Bone Disease / Soft Tissue Calcification
ParaThyroid Gland
CKD - Mineral & Bone Disease
3 Receptors;
Vitamin D + FGF-23
Ca-Sensing Receptor = CaSR
main regulator of PTH
PTH = Maintains Calcium Levels
Acts on:
Kidney / Intestine / Bone
Directly Stimulated by:
HypoCalcemia, PTH –> CaSR on PTGland
PTH Action on
KIDNEY
HypoCalcemia –> PTH release –> CaSR receptors on PTGland
- *Kidney:**
- *↑ Renal Absorption of Ca**
↑Renal EXCRETION of Phos
↑Synthesis of Calcitriol
PTH Action on
INTESTINE
HypoCalcemia –> PTH release –> CaSR receptors on PTGland
indirectly:
↑Absorption of BOTH
Ca & P
in small intestine
PTH Action on
BONE
HypoCalcemia –> PTH release –> CaSR receptors on PTGland
↑OsteoClasts
breakdown bone –> MORE Calcium
_↓OsteoBlasts_
inhibit “building” = bone formation
Secondary HyperParathyroidism
Causes an INCREASE in PTH due to WHAT?
↑PTH due to:
_↓serum Ca_ & ↓production of Calcitriol
indirectly ↑Phos
Progressive & starts @ GFR < 60 (CKD)
VVV
leads to HYPERplasia of Parathyroid Gland
lose sensitivity to:
CaSR & VDR
possible adenomatous transformation of the gland
–> HYPERcalcemia in some patients
- *Reduction in GFR**
- Nephron LOSS*
has WHAT EFFECTS on
PTH
Phosphorus
Calcium
Calcitriol
↑PTH & ↑PHOS
↓CALCIUM*** & ↓***Calcitriol
FGF-23
What Increases its production?
What is its function?
↑Phosphate & ↑Calcitriol [1,25(OH)2D]
leads to release of–> ↑FGF-23
FGF-23 –> feedback loop ↓Calcitriol
by supressing 1-a-hydroxylase @ proximal tubule
FGF-23 regulates:
Phosphate & Vitamin D homeostasis
&
INHIBITS PTH PRODUCTION
Consequences of HYPERParaThyroidism
- *#1 = CARDIOVASCULAR ISSUES**
- Artery calcification –> ↑*Atherosclerotic load–> ↑MI risk
Vascular Calcification
Osteoporosis
Anemia / Itching
Parathyroidectomy
hungry bone syndrome / recurrence of HYPERparathyroidism
Types of Bone Disease
&
How are they Classified?
Dependent on the :
Degree of Abnormal bone turnover & imparied mineralization of the extracellular matrix
Osteitis Fibrosa Cystica
Adynamic Bone Disease
MIXED Uremic Bone Disease
Osteomalacia
Which type of BONE DISEASE?
Occurs when PTH is constantly ELEVATED
Woven Appearance
caused by increased # of osteoid
Accelerated formation & resorption of bone due to:
INCREASED # & activity of
OsteoClasts/Blasts+Marrow Fibrosis
- *OSTEITIS FIBROSA CYSTICA**
- *iPTH > 300**
WOVEN
Constant PTH elevation
INCREASED:
OsteoClasts + OsteoBlasts + OSTEOID + Marrow Fibrosis
Which type of BONE DISEASE?
HIGH CALCIUM & *low PTH levels (<150)*
Occurs from the:
- Supression of PTH* via
- *Phos Binders / Vit D treatment / Calcimimetics**
low turnover bone state
normal or reduced Osteoid thickness
no mineralization defect
low Osteoclasts & osteoblasts
ADYNAMIC BONE DISEASE
- low everything*, except for Calcium
- PTH / osteioid / osteoclasts+blasts*
Treatment:
_D/C or *reduce* dose of
Vitamin D or Calcimimetic_
since it is caued by the supression of PTH by:
phos binders / vit D / calcimemetics
EXTRAskeletal Presentation
of CKD - Bone Disease
occurs from
HIGH CA & PHOS
Medical OVERsupression of PTH by VIT D
inefficient incoportation of Ca -> bone
leading to vascular calcification
HEART
leads to widened pulse pressure / increased AFTERLOAD & LVH
SKIN –> CALCIPHYLAXIS
MusculoSkeletal Presentation
of CKD - Bone Disease
FRACTURES
hip fracture, highest incidence in stage 5
Tendon Rupture** + **Bone Pain
Calcification of VESSELS
frequent in stage 5, only INCREASES the longer on dialysis
large effects on:
blood vessels / heart valves / SKIN
Mineral & Bone Disease Goals
Stage 5
is where Phos + Calcium levels CHANGE
HYPERPhosphatemia
CKD - Mineral & Bone Disease
↑Phos -> ↑PTH & ↓Calcitriol Synthesis
Most Phos comes from FOOD, dialysis is unable to remove it
Need:
*LOW phos Diet* + PHOS BINDER
Symptoms:
Pruritis, Rash / Bone+Joint Paint / Muscle Cramps + Tetany
HIGH Phosphorus leads to what?
indirectly-> ↑PTH Production
&
↓Inhibits CALCITRIOL synthesis
PHOSPHORUS BINDERS
Important Counseling Advice
- dependent on DIETARY phos control:*
- *800-1000 mg/day**
try and AVOID:
_Calcium Based products_
due to HYPERcalcemia
- *TAKE WITH FOOD**
- do NOT take if NOT eating*
Seperate from certain Meds
Antibiotics / LEVOthyroxine
Caution in patients with:
Bowel Obstruction / Ileus-Fecal Impaction / Hypomotility Disorders
Calcium Carbonate
OTC Phosphorus Binder
Try not to use CALCIUM BASED products, due to hypercalcemia, ExtraSkeletal Calcification
1-2 Tabs
WITH EACH MEAL
Max 7 Tabs of TUMS
Calcium Acetate
PRESCRIPTION Phosphorus Binder
- Try not to use CALCIUM BASED products*, due to hypercalcemia
- ExtraSkeletal Calcification*
- *GREATER PHOS BINDING** > Ca Carbonate
- but is RX only*
2 caps w/ each meal
Sevelamer Carbomate/HCL
RENVELA / RENAGEL
- *Phosphorus Binder**
- *PREFERRED -> does NOT induce ACIDOSIS**
Tabs or Packets
_SEPERATE FROM:
Mycopehnolate / Cyclosporine / Tacrolimus_
- CONSTIPATION*
- nausea / vomiting / diarrhea / dyspepsia*
Lanthanum Carbonate
Phos Binder
Chewable or Powder
Must be taken WITH or AFTER meals
ab pain / NV
Sucroferric Oxyhydroxide
Velphoro
Phos Binder
- *Chewable Tabs**
- minimal Fe absorption*
- DARKENING OF STOOLS*
- diarrhea / constipation / NV*
SEPERATE FROM VITAMIN D
Ferric Citrate
Auryxia
Phos Binder
INCREASES TSAT
do NOT use in IRON OVERLOAD
DARKENING OF STOOLS
diarrhea / constipation / NV
What Drugs do we need to seperate from
Phos Binders?
- *Antibiotics**
- *Tetracyclines + Fluoroquinolones**
Levothyroxine
For Sevelamer:
Mycophenolate / Cyclosporine / Tacrolimus
for Sucroferric Oxyhydroxide:
PO Vit D
Aluminum for Phos Binding
not used often:
Only in in EMERGENT situations
or
P > 7mg/dL
Al-OH or Al-Carbonate
Use no longer than < 4 weeks, due to toxicities:
bone / bone marrow / CNS
iPTH
- *Directly Measures Parathyroid Gland FXN**
- Indirectly Measures* Bone Remodeling
- NOT ACCURATE ASSAY*
- *–> better to LOOK AT TRENDS** rather than individual result
iPTH > 300 = possible Osteitis Fibrosa Cystica
iPTH <150 = possible adynamic bone disease
Vitamin D & Vitamin D Analogues
(Calcitriol)
For:
CKD - Mineral & Bone Disease
KDOQI: Only use if:
- *Ca <9.5** — P <5.5
- still used in practice though*
Vitamin D –> supresses PTH
Increases:
- *Gut Absorption of PHOSPHORUS**
- *AND CALCIUM**
caution with HYPERphosphorus
Comparible Doses of
Calcitriol / Viamin D Analogs
“Alphabetical Order - 1 - 2 - 4”
Calcitriol - 1 mcg
MOST HYPER-Ca & HYPER-Phos
DoxerCalciferol - 2 mcg
Pro-drug, less HYPERcalcemic, PO is MORE HYPERcalcemic vs IV
- *Paricalcitol -** 4 mcg
- least hypercalcemic & hyperphosphatemic*
Cinacalcet = Sensipar
30/60/90 mg tablets
Taken with food & WHOLE
adjust dose in 4 weeks
USES
reduce PTH
by ↑CaSR sensitivity on PT Gland
- *Ca needs to be > 8.4mg/dL**
- may cause HypoCalcemia*
Uses:
- *PTH is NOT controlled by VitD Analogs**
- *HYPERcalcemia** / Calciphylaxis
ensure med is held 12 hours b4 PTH lab draw
can have FALSELY low PTH levels
Cinacalcet = Sensipar
ADR / Precautions / Drug Interactions
TAKEN WHOLE & WITH FOOD
Vomiting / Diarrhea / Nausea
Precaution:
SEIZURES –> associated with low Calcium
DI:
- *Strong Inhibitor of CYP2D6
- partially metabolized by 3A4***
Etecalcetide = Parsabiv
MoA / Uses
Binds to CaSR
and enhances its activation by extracellular calcium
ONLY FOR HEMODIALYSIS PATIENTS
IV formulation –> need to restart to 5mg/ML if missed dose
Calcium should be >8.4 b4 starting
check q4weeks
Etelcalcetide
ADR / Concerns
only for HEMODIALYSIS patients
IV, store in FRIDGE
ADR:
- HypoCalcemia* –> Worsening heart Failure
- possible IMMUNOGENECITY –> AB formation*
Better GI Tolerance > Cinacalcet
Switching From Cinacalcet –> D/C for 7 days pror
Inactive Vitamin D
Serum 25(OH)D goal level > 30 ng/mL
not for Adjusting PTH
role mainly for preventing:
cancer / diabetes / Autoimmune dzs / CV dzs / infxns
Treatments:
Ergocalciferol 50k units qweek - q2week - qmonth
Cholecalciferol 1k-5k QD
- *Calcifediol = Rayaldee** 30mcg pq qHS
- drug interactions with CYP3A & THIAZIDE diuretics*
Mineral & Bone Disease Goals
KDOQI - CKD Stage 3 & 4
Both the SAME for Phos & Ca (normal ranges)
Phos = 2.7 - 4.6
Corrected Ca = 8.4 - 10.2
Ca x P = —-
CKD 3 iPTH = 35 - 70
CKD 4 iPTH = 70 - 110
Mineral & Bone Disease Goals
KDOQI - CKD Stage 5
Phos = 3.5 -5.5
Corrected Ca = 8.4 - 9.5
Ca x P = < 55
iPTH = 150 - 300
Mineral & Bone Disease Goals
KDIGO 2017
CKD G5D
iPTH
2-9x Upper Limit
~150 - 600
Phos: lower towards normal range
Ca = AVOID HYPERcalcemia
