Transcript hyperparathyroidism in chronic kidney disease

Hyperparathyroidism in
Chronic Kidney Disease
醫五 李政霆
Three major possible targets
regulate parathyroid gland function
• G-protein-coupled calcium-sensing
receptor (CaSR)
• Vitamin D receptor (VDR)
• Putative extracellular phosphate sensor
Kidney failure
1. Decreased renal excretion of phosphate
and diminished renal hydroxylation of 25hydroxyvitamin D to calcitriol (1,25dihydroxyvitamin D).
2. Disrupts systemic calcium and
phosphate homeostasis and affects the
bone, gut, and parathyroid glands.
Hypocalcemia and the calciumsensing receptor
1. CaSR: Which is highly expressed in the
parathyroid glands
2. The fall in serum calcium concentration
with renal failure, as sensed by the
CaSR, is a potent stimulus to the release
of PTH
Decreased vitamin D levels
1. Vitamin D stimulates intestinal phosphate
absorption
2. Decrease in active vitamin D production
may be viewed as an adaptive response
to minimize hyperphosphatemia
Hyperphosphatemia
1. A novel phosphaturic factor, FGF23, may
be regulated by phosphate and vitamin D
2. Lowers the levels of ionized calcium,
interferes production of 1,25dihydroxyvitamin D, resulting in
increased PTH levels
Renal osteodystrophy
1. Osteitis fibrosa cystica
(a) Increased bone turnover activity
(b) Bone pain and increased risk of fracture
2. Adynamic bone disease
(a) Decreased bone turnover activity
(b) Excess suppression of parathyroid gland
therapies, particularly Ca-containing
phosphate binders and vitamin D analogues
Calciphylaxis
eMedicine
Calciphylaxis
eMedicine
Figure 1. The factors involved in the pathogenesis of secondary hyperparathyroidism
Martin, K. J. et al. J Am Soc Nephrol 2007;18:875-885
Copyright ©2007 American Society of Nephrology
K/DOQI Recommendation
Plasma PTH
Serum Ca
Serum P
Ca*P
Stage3 35 to 70
pg/mL
8.4 to 10.4 2.7 to 4.6 <55
mg/dL
mg/dL
mg2/dL2
Stage4 70 to 110
pg/mL
8.4 to 10.4 2.7 to 4.6 <55
mg/dL
mg/dL
mg2/dL2
Stage5 150 to 300 8.4 to 9.5
pg/mL
mg/dL
3.5 to 5.5 <55
mg/dL
mg2/dL2
Management of secondary HPT in
dialysis patients
• Phosphate binders (calcium or noncalcium containing binders)
• Vitamin D analogues
• Calcium supplementation and/or a
calcimimetic
Stepped strategy
• Normalizing serum phosphate levels
• Limiting excessive calcium loading
• Using a calcimimetic in patients with
elevated PTH levels
• Avoiding high dose active vitamin D
analog administration and reducing
vitamin D analog dose in patients with
suppressed PTH levels
Step 1
• Measure serum calcium, albumin,
phosphate, 25(OH) vitamin D and intact
PTH levels
Step2
• Treating hyperphosphatemia without
causing hypercalcemia
＊ Hyperphosphatemia is associated with:
a. Increased mortality in ESRD
b. Phosphate is the principal factor
leading to calcification
Step 2
(I) P <5.5 mg/dL and Ca <9.5 mg/dL：
1.Calcium-based phosphate binders, either
calcium carbonate or calcium acetate
should be started
2.Keeping daily elemental calcium intake
from binders to less than 1500 mg, and
total elemental calcium from diet and
binders to less than 2000 mg.
Step 2
(II) P <5.5 mg/dL and Ca >9.5 mg/dL ：
No phosphate binder is necessary.
(III) P >5.5 mg/dL and Ca >9.5 mg/dL ：
A non-calcium containing phosphate binder
should be used
Step 2
(IV) P >5.5 mg/dL and Ca <9.5 mg/dL ：
1. Calcium-based phosphate binder used
2. Adding a non-calcium containing
phosphate binder if phosphate remains
above 5.5 mg/dL
Step 3
•
Decide whether phosphate binder
therapy is sufficient or whether a
calcimimetic or vitamin D analogue
should be added ：
1. If PTH<300 pg/mL，no additional
therapy needed
2. If PTH>300 pg/mL with binder therapy，
the choice is either cinacalcet or vitamin
D analogues
Step 3
• If the calcium and phosphate levels are
both toward the upper limit：
starting cinacalcet
• If the calcium level is near or below the
lower limit and the phosphate is well within
the normal range：
Vitamin D should be used
• Cinacalcet：
Suppressing serum PTH levels without
raising the Ca x P product
• Vitamin Danalogues:
Induce hyperphosphatemia,
hypercalcemia and promote vascular
calcification at high doses
• P >5.5 mg/dL and Ca >8.4 mg/dL
P <5.5 mg/dL and Ca >9.5 mg/dL
Use Cinacalcet
• P <5.5 mg/dL and Ca <9.5 mg/dL
Use vitamin D analogue
Step 4
• Adjust the doses of phosphate binders,
active vitamin D, and cinacalcet to attempt
to attain K/DOQI target values