Transcript Slide 1

Uncontrolled secondary
hyperparathyroidism in a
haemodialysis patient
Jordi Bover, MD, PhD
Fundació Puigvert
Barcelona, Spain
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Objectives
● The systemic manifestations of chronic kidney diseasemineral bone disorder (CKD-MBD)
● The treatment of uncontrolled secondary
hyperparathyroidism in CKD
CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral and bone disorder
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Chronic kidney disease-mineral and
bone disorder
● Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a
systemic disorder of mineral and bone metabolism due to CKD
manifested by either one or more of the following:
● Abnormalities of calcium, phosphorus, PTH, or vitamin D
metabolism
● Abnormalities in bone turnover, mineralisation, volume, linear
growth, or strength
● Vascular or soft tissue calcification
● Several biochemical abnormalities of CKD-MBD are associated with
reduced survival in dialysis patients
● Calcium, phosphate, PTH, Ca x P, alkaline phosphatase, FGF-23
● Combinations of high-low PTH, calcium and phosphate
● Time on target
Ca x P: calcium/phosphate product; CKD: chronic kidney disease; CKD-MBD: chronic-kidney disease-mineral and bone disorder;
FGF-23: fibroblast growth factor-23; PTH: parathyroid hormone
KDIGO CKD-MBD Work Group. Kidney Int. 2009 [Supp113]:S1–130
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Secondary hyperparathyroidism in CKD
● Secondary hyperparathyroidism is a common complication of
impaired renal function
●
●
●
Secondary hyperparathyroidism is associated with clinical complications
involving the bones and other tissues
Bone disease (renal osteodystrophy) is present in at least 70% of CKD patients
starting dialysis, although different patterns have been observed over time
Increased PTH is also associated with several “uraemic” conditions
● Treatment in secondary hyperparathyroidism aims to manage levels
of calcium, phosphate and PTH
●
●
Conventional therapy includes dietary reduction of phosphate intake, the use of
phosphate binders, hydroxylated vitamin D sterols or the synthetic vitamin D
analogue paricalcitol, and modification of the dialysis regimen
Calcimimetics increase the sensitivity of calcium-sensing receptors to
extracellular calcium ions, thereby inhibiting the release and synthesis of PTH
● Can be used as part of a therapeutic regimen including phosphate binders
and/or vitamin D sterols, as appropriate
CKD: chronic kidney disease; PTH: parathyroid hormone
National Institute for Health and Clinical Excellence. January 2007
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Patient presentation
• A 72-year-old female patient
— CKD stage 5D since 2007
— Uncontrolled secondary hyperparathyroidism
• Current therapy
— Paricalcitol: 10 g/haemodialysis
— Sevelamer: 4800 mg/day
• Haemodialysis treatment (early morning shift)
— Kt/V ≈ 1.4
— Dialysate calcium: 3 mEq/L
CKD: chronic kidney disease
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Multiple choice question 1
According to the KDIGO 2009 guidelines and the KDOQI US
Commentary on the 2009 KDIGO Clinical Practice Guidelines, which of
the following is an important laboratory parameter for monitoring
secondary hyperparathyroidism in patients with CKD stage 5D?
A.
B.
C.
D.
E.
Corrected serum calcium
Serum phosphorus
Alkaline phosphatase
Intact parathyroid hormone
All of the above
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Laboratory values for key secondary
hyperparathyroidism parameters
Parameter
Value
KDOQI
2003 Goals
KDIGO
2009
Range
Corrected calcium (mg/dL)
10.1
8.4-9.5
N
Phosphate (mg/dL)
5.6
3.5-5.5
“towards” N
Calcium/phosphate product
(mg2/dL2)
56.6
<55
iPTH (pg/mL)
820
150-300
-
>2-<9 ULN
iPTH: intact parathyroid hormone; KDOQI: Kidney Disease Outcomes Quality Initiative. KDIGO: Kidney Disease: Improving
Global Outcomes; N: normal; ULN: upper limit of normal
National Kidney Foundation. Am J Kidney Dis. 2003;42(suppl 3):S1-S201; KDIGO CKD-MBD Work Group. Kidney Int. 2009
[Supp113]:S1–130
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Additional laboratory values
Parameter
Value
Alkaline phosphatase (U/L)
160
Calcidiol (25-OH-vitamin D)* (ng/mL)
28
Calcitriol
N/A
Albumin (g/L)
41
Bicarbonate (mEq/L)
20
*With native vitamin D supplementation
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Multiple choice question 2
Which of the following statements is NOT correct regarding vascular
calcification according to the 2009 KDIGO guidelines on CKD-MBD?
A.
B.
C.
D.
Vascular calcification is exceedingly more prevalent, more severe,
and follows an accelerated course in the CKD population compared
with that in the normal population.
A lateral abdominal radiograph can not be used as an alternative to
computed tomography-based imaging to detect the presence or
absence of vascular calcification.
Patients with CKD stages 3-5D with known vascular calcification
should be considered at highest cardiovascular risk.
It is reasonable to use information on vascular/valvular calcification to
individualise treatment of CKD-MBD.
CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral and bone disorder;
KDIGO: Kidney Disease: Improving Global Outcomes
KDIGO CKD-MBD Work Group. Kidney Int. 2009 [Supp113]:S1–130
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Radiographic evaluation
• Radiographic studies showed evidence of vascular
calcifications in the arms (cubital and radial), hands and
pelvis, as well as in a lateral lumbar spine
Reprinted with permission from Dr. Bover
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Additional diagnostic evaluation
• Sestamibi scanning
— Radionuclide uptake in
the parathyroid gland
• DEXA bone densitometry
— Normal lumbar spine
— Femoral
osteopenia/osteoporosis
DEXA: dual-energy x-ray absorptiometry
Reprinted with permission from Dr. Bover
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Multiple choice question 3
According to the KDIGO guidelines, which of the following can be used
to lower PTH in patients with CKD stage 5D:
A.
B.
C.
D.
E.
Calcitriol
Vitamin D analogues
Calcimimetics
Combination of calcimimetics and calcitriol/vitamin D analogues
All of the above
CKD: chronic kidney disease; KDIGO: Kidney Disease: Improving Global Outcomes; PTH: parathyroid hormone
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Cinacalcet treatment: Titration and
monitoring
• Titration phase
— Week 1
•
•
•
•
Cinacalcet 30 mg/day added after lunch (main meal after HD)
Day 7: Calcium 9.8 mg/dL, Phosphorus 5.3 mg/dL
Day 14: Calcium 9.7 mg/dL, Phosphorus 5.4 mg/dL
Day 30: iPTH 450 pg/mL; Calcium 9.8 and Phosphorus 5.3 mg/dL
— Week 5
• Cinacalcet ↑ to 60 mg/day + paricalcitol ↓ to 5 μg/HD
• Day 7: Calcium 9.1 mg/dL, phosphorus 4.9 mg/dL
• Day 30: iPTH 310 pg/mL
• Maintenance phase
— Alternate regimen of cinacalcet 60/30 mg/day
— Eventually sevelamer dose was decreased
HD: haemodialysis; iPTH: intact parathyroid hormone
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Key learning points
• Combination of several treatments acting on different pathways may
become the best approach to the complex CKD-MBD
• Calcimimetics are an important option for patients with CKD-MBD
and uncontrolled secondary hyperparathyroidism
— Help control several biochemical markers, such as serum calcium, phosphate,
Ca x P, in addition to iPTH. Recently it has been described that calcimimetics
may decrease FGF-23 levels (related with mortality)
— Allow some patients to decrease the need for high-dose vitamin D derivatives
and phosphate binders
— Provide room for vitamin D derivatives in patients prone to hypercalcaemia or
hyperphosphataemia
— May increase the safe therapeutic window in patients with vascular calcification
— May be used in patients without severe secondary hyperparathyroidism
(specially if they have high serum and phosphorus values)
Ca x P: calcium/phosphate product; CKD-MBD: chronic kidney disease-mineral and bone disorder; FGF-23: fibroblast growth factor23; iPTH: intact parathyroid hormone
National Institute for Health and Clinical Excellence. January 2007
© Springer Healthcare, a part of Springer Science+Business Media; 2010.
Conclusion
• In this 72-year-old calcified patient with stage 5D CKD and
uncontrolled secondary hyperparathyroidism, treatment with
cinacalcet normalised several biochemical abnormalities associated
with CKD-MBD
• Calcimimetics represent a new class of drugs that control the
biochemical abnormalities of patients with secondary
hyperparathyroidism in dialysis
— Unique mechanism of action targets the biochemical
profile of CKD-MBD patients differently than other
available drugs
• While awaiting results of new clinical studies and economical
implications, calcimimetics provide an excellent therapeutic window
for combination therapy
CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral and bone disorder
© Springer Healthcare, a part of Springer Science+Business Media; 2010.