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description
Learning Objectives: • Describe the physiology of PTH and mineral metabolism in
patients with CKD • Discuss the available therapies for the disorders of PTH and
mineral metabolism in patients with CKD• Apply this information to the clinical management of patients
with CKD
PTH and Mineral Disorders in Patients With CKD: A Practical Case-Based
Approach for Renal Dietitians
Patient Case
• 53-year-old male with history of stage 5 CKD 2º ADPKD recently started on hemodialysis after failed renal transplant
• History of deceased donor renal transplant, 11/95
• Previously on hemodialysis, 6/95–11/95
• History of CVD, s/p CABG x 3 in 02/04
• History HTN; history basal cell carcinoma
• Social history: works as car mechanic; no history of alcohol, tobacco; married 21 years; 1 daughter, age 19
• Family history ADPKD on maternal side
Patient Case (cont)
• Presents with mild itching, bone pain• No history of fractures• Medications:
– Calcium acetate: 667 mg 3 tab tid– B-complex with C: 1 tab qd– Atorvastatin: 20 mg qd– Metoprolol: 50 mg bid– Prednisone: 2.5 mg qd
• Laboratory values:– Phosphorus: 8.0 mg/dl– Corrected calcium: 8.3 mg/dl– Intact PTH: 670 pg/ml– Ca x P: 66.4
• Concentration in blood/plasma is tightly regulated by PTH and vitamin D
• Calcium ions serve a variety of functions– Signal transduction: 1st and 2nd messengers
– Nerve and muscle function
– Major component of bone
• Serum calcium does not reflect total body calcium content
Overview of Calcium Physiology
Regulation of Plasma Calcium
PTglands
CaSR
Adapted from E Nemeth.
PTH
bone
PO4 reabsorption
Ca reabsorptionkidney
PTglands
CaSR
PO4 resorption
Ca resorption
Low plasma Ca2+
plasma Ca2+
intestine
1,25-dihydroxy-vitamin D3 PO4 absorption
Ca absorption
LiverLiver
KidneyKidney
SkinSkin
Pre-vitamin D
Vitamin D
7-dehydrocholesterol
25-OH calcidiol
1-hydroxylase
1,25 (OH)2 D
calcitriolmost potent metabolite
Low PO4
Low CaHigh PTH+
- High PO4
High CaLow PTH
Vitamin D Metabolism
DietDiet
Adapted from WG Goodman.
Principal Biological Effects of Vitamin D
• Increases absorption of Ca and P
• Maintains bone mineralization and turnover
• Indirectly reduces synthesis of calcitriol
• Reduces synthesis of PTH
Acute and Chronic Regulation of PTH Output
PROCESS TIME FRAME FACTORS
PTH secretion minutes Ca2+/CaSR
Gene expression
Transcription
mRNA stability
hours, days
Vit D / VDR VDRE
Ca2+ CaRE
low Ca (↑ half-life)
low PO4 (↓ half-life)
Tissue hyperplasiaweeks,
months, years
Ca2+/CaSR PO4
• Normal PO4 levels in plasma: 2.5–4.5 mg/dL1
• Total body PO4 content: 500–700 g1 (85% in bone)
• Dietary Reference Intake2: 700 mg
• Typical US dietary intake2: 1200 mg
• GI absorption Mainly passive, through Na/Pi transporter Fractional absorption 60–70% Enhanced by vitamin D
• Kidney is major regulator3 Mediated by brush border Na/Pi transporter PTH – increases excretion Vitamin D – decreases excretion
1. Merck Manual. 2006;Sec 2:Ch 12. 2. Food & Nutrition Board, Institute of Medicine. Washington D.C.: National Academy
Press; 1997:146-189. 3. Takeda E, et al. Adv Enzyme Regul. 2000;40:285-302.
Phosphorus Metabolism
Phosphorus Homeostasis
1200 mg
500 mg
130 mg700 mg
(< 1%)
(85%)
(15%)
Soft tissues
PlasmaBone
Kidney
Intestine
700 mg
Adapted from: Goodman WG. Med Clin North Am. 2005;89:631-647.
Physiology Summary
• PTH and vitamin D are central regulators of plasma Ca
• Calcium regulates serum PTH through the parathyroid CaSR
• PTH production is controlled at several levels:
• Kidney is crucial for calcitriol synthesis and phosphate secretion
• Calcitriol increases serum calcium through increased intestinal absorption
Calcium Vitamin D
Secretion
mRNA level
Hyperplasia
Secondary HPT Pathophysiology:Overview
• CKD disrupts calcium homeostasis High PTH Low calcitriol Reduced intestinal calcium absorption Low serum calcium at low GFR High serum phosphorus at low GFR
• Excess PTH synthesis and secretion Inhibition of PTH transcription is deficient Hyperplasia and parathyroid gland enlargement
contribute to elevated serum PTH
Serum Analytes Vary With Stage of Kidney Disease
Craver L, et al. Nephrol Dial Transpl. 2007;22:1171-1176..
50
40
30
20
10
0 CKD1 CKD2 CKD3 CKD4 CKD5
N = 15 87 221 156 43
1,25
-(O
H) 2
D (
pg
/mL
)
i PT
H (
pg
/mL
)
CKD1 CKD2 CKD3 CKD4 CKD5
N = 174 341 856 354 111
0
200
100
**
**
*
**
*P < 0.05
LLN ULN
LLN
Serum Analytes Vary With Stage of Kidney Disease (cont)
CKD1 CKD2 CKD3 CKD4 CKD5
N = 174 341 856 354 111
9.7
9.6
9.5
9.4
9.3
9.2
9.1
9.0
8.9
Ser
um
Cal
ciu
m (
mg
/dL
)
CKD1 CKD2 CKD3 CKD4 CKD5
N = 174 341 856 354 111
Ser
um
Ph
osp
hat
e (m
g/d
L)
5.5
5.0
4.5
4.0
3.5
3.0
*
*P < 0.05
*
*
All calcium values within normal range
ULN
Craver L, et al. Nephrol Dial Transpl. 2007;22:1171-1176.
Pathophysiology of sHPT in CKD
↓ 1,25(OH)2D3↑ P
Adapted from Skorecki K, et al. Harrison’s Principles of Internal Medicine. 15th ed. 2001:1551-1562.
↑ PTH
↓ Ca2+
1
1.5
2
0.9
All-
Cau
se D
eath
Haz
ard
Rat
io
Serum iPTH (pg/mL)
KDOQI recommended
range: 150-300 pg/mL
Risk of Death by Quarterly Varying iPTH
< 10
0
100-
200
200-
300
300-
400
400-
500
500-
600
600-
700
700
Time-dependent Case-Mix and MICS model
Kalantar-Zadeh K, et al. Kidney Int. 2006;70:771-780.
Corrected Serum Calcium (mg/dL)
< 8.0 8.0 to8.5
8.5 to9.0
9.0 to9.5
9.5 to10.0
10.0 to10.5
10.5 to11
11.00.7
2
3
1
All-
Cau
se D
eath
Haz
ard
Rat
io
8.0 to0.7
2
3
1
0.7
2
3
1
0.7
1.5
2
3
1
Risk of Death by Quarterly Varying Albumin-Adjusted Calcium
KDOQI recommended
range 8.4-9.5 mg/dL
Time-dependent Case-Mix and MICS model
Kalantar-Zadeh K, et al. Kidney Int. 2006;70:771-780.
Risk of Death by Quarterly Varying Phosphorus
0.7
2
3
4
1
Serum Phosphorus (mg/dL)
2
3
4
1
2
3
4
1
2
3
4
1
< 3.0 3.0 to3.99
4.0 to4.99
5.0 to5.99
6.0 to6.99
7.0 to7.99
8.0 to8.99
9.0
KDOQI recommended
range: 3.5-5.5 mg/dL
All-
Cau
se D
eath
Haz
ard
Rat
io
Kalantar-Zadeh K, et al. Kidney Int. 2006;70:771-780.
Time-dependent Case-Mix and MICS model
Clinical Consequences of Mineral Dysregulation
• Renal osteodystrophy
• Hyperphosphatemia
• Cardiovascular calcification
• Extraskeletal calcification
• Endocrine disturbances
• Neurobehavioral changes
• Compromised immune system
• Altered erythropoiesis
Forms of Vascular Calcification
London GM et al. Curr Opin Nephrol Hypertens. 2005;14:525–531.
Arterial Calcification
Intimal Calcification
Atherosclerosis
Stenosis, occlusions
Infarction, ischemia
Medial Calcification
Arteriosclerosis
Stiffening
Systolic and pulse pressures, early return of wave reflections
Altered coronary perfusion, left-ventricular
hypertrophy
Risk Factors for Soft Tissue Calcification
• Hyperphosphatemia
• Increased Ca x P product
• Excessive calcium load
• Secondary hyperparathyroidism
• Local tissue injury
• Rise in tissue pH
• Decreased levels of calcification inhibitors
• Systolic hypertension (average 1 year systolic bp 160 mm Hg vs 120)
• Adipose tissue (calcific uremic arteriolopathy)
Vascular Calcification in ESRD
Intimal CalcificationAtherosclerosis
Medial CalcificationArteriosclerosis
Available at: http://library.med.utah.edu/WebPath/CVHTML/CV007.html. Accessed May 2007.
Impact of Arterial Calcification in Stable Hemodialysis Patients with ESRD
London GM, et al. Nephrol Dial Transplant. 2003;18:1731.
Car
dio
vasc
ula
r S
urv
ival
2 = 34.9; P < 0.0001
0 25 50 75 1000.00
0.75
0.50
0.25
1.00
Time (months)
NCP < 0.01
P < 0.001
AMC
AIC
2 = 44.3; P < 0.00001
0 25 50 75 1000.00
0.75
0.50
0.25
1.00A
ll-C
ause
S
urv
ival
NC
P < 0.001
P < 0.01
AMC
AIC
0
0.25
0.5
0.75
1
0 20 40 60 80
Follow-up (months)
Probability of Survival
0 Arteries Calcified
1 Artery Calcified
2 Arteries Calcified
3 Arteries Calcified
4 Arteries Calcified
N = 110 stable dialysis patients with ESRD
P < 0.0001 comparison among groups
Blacher J, et al. Hypertension. 2001;38:938-942.
Probability of Survival Decreases With Increasing Arterial Calcification
Valvular Calcification and Mortality
† P < 0.0005 vs no valvular calcification
0
0.2
0.4
0.6
0.8
1.0
0 6 12 18 24 30 36
Ove
rall
Su
rviv
al
Both Mitral and Aortic (n = 14)
Either Mitral or Aortic (n = 48)
Neither (n = 130)
Follow-Up Time (months)
†
Wang A, et al. J Am Soc Nephrol. 2003;14:159-168.
CAC Is Associated With Increased Mortality
Block GA, et al. Kidney Int. 2007;71:438-441.
0 6 12 18
CAC = 0CAC1 – 400CAC 400
240.00
0.25
0.50
0.75
1.00
30 36 42 48 54 60 66
P = 0.002
Months
Su
rviv
al D
istr
ibu
tio
n F
un
ctio
n
Calcification in Vascular Smooth Muscle Cells
Osteo/Chondrocytic VSMC
Death Signal VSMC Damage“Uremic Milieu”
Apoptotic Bodies
Matrix Vesicles
+ MGP / BMP7+ fetuin-A+ PPi
- MGP/ BMP2- fetuin-A- PPi/+ALK+ Ca/P
ClearanceCalcification
PhagocytosisDelayed or Impaired
Phagocytosis
Elastin
Shanahan CM. Curr Opin Nephrol Hypertens. 2005;14:361–367.
Vascular Calcification, Cardiovascular Complications, and CKD
• Vascular Calcification Associated With: – Accelerated risk of stroke, amputation, MI– Left ventricular hypertrophy– Poor coronary artery perfusion– Increased pulse wave velocity– Increased pulse pressure
• Contributory Factors:– Deranged bone and mineral metabolism– Decreased levels of inhibitors of calcification such as fetuin-A– Stimulation of osteogenic pathways in endothelial cells by
uremic “toxins” – Impaired endothelial repair mechanisms
Adapted from Lederer E and Ouseph R. Am J Kidney Dis. 2007;49:162-171.Block GA, et al. Kidney Int. 2007;71(5):438-441.
Serum PTH 150–300 pg/mLSerum Ca (albumin-corrected) 8.4–9.5 mg/dL
Serum P 3.5–5.5 mg/dLCa x P Product < 55 mg2/dL2
National Kidney Foundation. Am J Kidney Dis. 2002;39(Suppl 1):S1-S266.
KDOQI™ Goals for Stage 5 CKD
KDOQI guidelines recommend that Ca2+ and P should be monitored monthly and PTH quarterly after stabilization.
Patient Case Review/Update
• Medications: – Calcium acetate: 667 mg 3 tab tid– B-complex with C: 1 tab qd– Atorvastatin: 20 mg qd– Metoprolol: 50 mg bid– Prednisone: 2.5 mg qd
• Laboratory values:– Phosphorus: 8.0 mg/dl– Corrected calcium: 8.3 mg/dl– Intact PTH: 670 pg/ml– Ca x P: 66.4
Nutrition Guidelines
• Limit dietary phosphorus to 800-1000 mg/d with consideration for protein needs, ie, as low as possible while allowing for a recommended level of protein intake
• Limit elemental calcium from calcium-based binders to ≤ 1500 mg/d
• Limit total (dietary and medication) elemental calcium to ≤ 2000 mg/d
• Avoid calcium fortified foods as directed
• Moderate application of cardiovascular dietary recommendations, not to the detriment of nutrition status
National Kidney Foundation. Am J Kidney Dis. 2002;39(Suppl 1):S1-S266.
Lifestyle Guidelines
• Exercise training
• Identify and address psychological issues (eg, depression)
• No smoking (help prevent CVD?)
Patient Case Review/Update
• Patient started on sevelamer HCl 800 mg 2 tablets tid with meals, Ca acetate discontinued to reduce vascular calcification risk
• Repeat labs after 2 weeks:
– Phosphorus: 6.5 mg/dl
– Corrected calcium: 8.3 mg/dl
– Ca x P: 54
• Diet reviewed; sevelamer increased to 3 tablets with meals, 2 tablets with snacks
Intervention Result
CaCa
PO4PO4
PTHPTH
Phosphate Binders
(Ca-based)
Therapeutic Interventions forManaging Secondary HPT
Adapted from Goodman WG. Nephrol Dial Transplant. 2003;18(suppl 3):iii2-iii8.
Managing Mineral Balance: Phosphate Binders
Sevelamer label: http://www.renagel.com/docs/renagel_pi.pdfBlock GA, et al. Kidney Int. 2007;71(5):438-441.
Serum Phosphate
SevelamerCalcium
Mortality
Ph
os
ph
oru
s C
ha
ng
e
Study Week
0 2 6 10 14 18 22 26 30 34 38 42 46 52
-5
-4
-
3
-2
-1
0
1
2
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42 48 54 60 66
P = 0.016
Su
rviv
al
Fra
cti
on
SevelamerCalcium
Months
Use of Phosphate Binders
• Ca-based binder should not be used if patient has hypercalcemia or PTH < 150 pg/mL
• Non-Ca-based binder preferred if vascular or soft-tissue calcification is appreciable
1st line 2nd line 3rd line
Stage 3/4 Dietary P restriction Ca-based binder
Stage 5
Dietary P restriction,
Ca-based
or
other binder
Ca-based
and
other binder
Al-OH up to 4 wks
National Kidney Foundation. Am J Kidney Dis. 2002;39(Suppl 1):S1-S266.
Phosphate Binders: Summary
Cannata-Andia JB. Dial Trans. 2002;17(Suppl 11):16–19; Ritz EJ. J Nephrol. 2005;18;221-228. Goodman WG. Neph Dial Trans. 2003;18(Suppl 3):iii2-iii8; Block GA, et al. Kidney Int. 2007; 71(5):438-441.
Binder Advantages Disadvantages
Aluminum-containing Effective
Tissue accumulation;
Bone disease, encephalopathy, anemia
Calcium-containing
Effective;
Widely used
Hyper-Ca, calcification risk;
High pill burden
Sevelamer
Less vascular calcification than Ca-containing binders; lower
mortality?
Reduction of TC & LDL
High pill burden
(moderate potency);
Cost; Tolerability
Lanthanum carbonate
Good potency;
Minimal absorption;
Not Hyper-Ca; Low pill burden
Cost; Taste fatigue; Unknown long term impact; Tolerability
Magnesium carbonate Potential to minimize Ca load Hyper-Mg; no long term
studies
Patient Case Update
• At 1 month, labs are checked
– Phosphorus: 5.5 mg/dL
– Corrected calcium: 8.3 mg/dL
– Ca x P: 46
– Intact PTH: 601 pg/mL
– 25-hydroxy vitamin D: 18 ng/mL
• Started on Vitamin D
– Ergocalciferol: 50,000 IU/month
– Active analog
Intervention Result
CaCa
PO4PO4
PTHPTHVitamin D
analog
Therapeutic Interventions forManaging Secondary HPT
Adapted from Goodman WG. Nephrol Dial Transplant. 2003;18(suppl 3):iii2-iii8.
Vitamin D Repletion in Stage 3 & 4 with Ergocalciferol: KDOQITM Recommendation
Serum 25(OH)D
(ng/mL)
Vitamin D Status Dose (IU) Route Duration
(months) Comment
< 5 Severe deficiency
50,000/wk X 12 wks; then
monthlypo
6
Assay 25(OH)D after 6 months
500,000 once im
Assure pt adherence;
assay 25(OH)D at 6 months
5-15 Mild deficiency
50,000/wk X 4 wks, then
monthlypo 6 Assay 25(OH)D
after 6 months
16-30 Insufficiency 50,000/mo po 6
National Kidney Foundation. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.
Sprague SM, et al. Kidney Int. 2003;63:1483-1490.
Vitamin D Analogs Suppress PTH
Time (weeks)
PT
H (
pg
/mL
)
0
100
200
300
400
500
600
700
800
900
1000
Paricalcitol (n = 130)
Calcitriol (n = 133)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Vitamin D (n = 37,173)
No Vitamin D (n = 13,864)
Teng M, et al. J Am Soc Nephrol. 2005;16:1115-1125.
*P < 0.001
8
15
CVMortality
*
*
14
29
0
10
20
30
40
50
2-YearMortality
Mo
rtal
ity
per
100
Pat
ien
t-Y
ears
Infectious Cause Mortality
13*
Vitamin D Use Is Associated With Decreased Mortality in Incident HD Patients
Which Vitamin D Do We Use and Why?
• Calcitriol (Calcijex®, Rocaltrol®) active vitamin D
– Increased calcium and phosphorus absorption
– Increased serum levels
– Loses effectiveness with high serum P
• Paricalcitol (Zemplar®) active vitamin D analog
– Less calcemic
• Doxercalciferol (Hectorol®)
– Less calcemic
Recommended Vitamin D Dosing
PTH Ca P Ca x P Calcitriol Paricalcitol Doxercalciferol
300 – 600 < 9.5 < 5.5 < 55 IV 0.5 – 1.5
Oral same
2.5 – 5.0 mcg IV 2 mcg
Oral 5 mcg
600 – 1000 < 9.5 < 5.5 < 55 IV 1.0-3.0
Oral 1-4
6.0 – 10 mcg IV 2 – 4 mcg
Oral 5 – 10 mcg
> 1000 < 10 < 5.5 < 55 IV 3.0-5.0
Oral 3-7
10 – 15 mcg IV 4 – 8 mcg
Oral 10 - 20 mcg
• Serum Ca > 10.2 : stop all D, minimize Ca load• Ca = 9.5-10.2: change to non Ca-containing binder• Ca < 9.5: continue D or modify with P algorithm • P > 6.0: stop vitamin D• P = 5.5–6.0: increase binders, decrease Vitamin D• P < 5.5: continue or modify using Ca or PTH algorithm
National Kidney Foundation. Am J Kidney Dis. 2002;39(Suppl 1):S1-S266.
• Laboratory data in one month:– Phosphorus: 6.1 mg/dl
– Calcium: 9.3 mg/dl
– Ca x P product: 57
– Intact PTH: 489 pg/ml
• Patient started on cinacalcet HCl 30 mg qd
Patient Case Update
Intervention Result
CaCa
PO4PO4
PTHPTHCalcimimetic
Therapeutic Interventions forManaging Secondary HPT
Adapted from Goodman WG. Nephrol Dial Transplant. 2003;18(suppl 3):iii2-iii8.
Targeting PTH Secretion With Cinacalcet
Control
Ser
um
PT
H (
% o
f m
axim
um
)
80
60
40
20
100
0 1.5
0
0.5 1.0 2.0
Extracellular Calcium (mM)
Cinacalcet
Cinacalcet Increases Calcium
Sensitivity
[Ca2+]ER [Cai2+]
CaSR
PTH
PTH
PTH
Cinacalcet
Adapted from Goodman WG, et al. Kidney Int. 1996;50:1834-1844.
Cinacalcet is Associated with a Reduction of PTH
Block GA, et al. New Engl J Med. 2004;350:1516-1525.
P < 0.001
Placebo
Cinacalcet
Dose titration Efficacy assessment
Week
PT
H le
ve
l (p
g/m
l)
800
700
600
500
400
300
200
100
00 2 4 6 8 10 12 14 16 18 20 22 24 26
~50
% r
edu
ctio
n
Cinacalcet Enables Patients to Achieve the KDOQI™ Targets
Adapted from Moe SM, et al. Kidney Int. 2005;67:760-771.
Me
dia
n i
PT
H (
pg
/mL
)
KDOQI™ Target
0
100
200
300
400
500
600
700
Week
Cinacalcet HCIPlacebo
n = 471n = 663
n = 366n = 473
B 2 4 6 8 12 14 16 18 20 22 24 2610
iPTH
Weekn = 471n = 663
n = 368n = 471
B 2 4 6 8 12 14 16 18 20 22 24 2610
Me
dia
n S
eru
m C
a (
mg
/dL
)
8.2
8.4
8.8
9.0
9.2
9.6
9.8
10.2
8.6
9.4
10.0
KDOQI™ Target
Serum Calcium
n = 410n = 547
n = 412n = 555
Weekn = 471n = 662
n = 363n = 466
B 2 4 6 8 12 14 16 18 20 22 24 2610
Me
dia
n C
a x
P (
mg
2/d
L2)
40
45
50
55
60
65Ca x P
KDOQI™ Target
n = 408n = 545
n = 363n = 466
Weekn = 471n = 663
B 2 4 6 8 12 14 16 18 20 22 24 26104.6
4.8
5.0
5.2
5.4
5.6
5.8
6.0
6.2
6.4
Me
dia
n S
eru
m P
(m
g/d
L) Serum Phosphorus
KDOQI™ Target
n = 409n = 547
Moe SM, et al. Nephrol Dial Transplant. 2005;20:2186-2193.
Cinacalcet Reduction of iPTH for 3 Years
Placebo n = 17
Cinacalcet n = 16
Cinacalcet Is Associated With Improved Outcomes
Cunningham J, et al. Kidney Int. 2005;68:1793-1800.
CV Hospitalization
FracturesPTX
Mortality
Week
Eve
nt-
Fre
e P
rob
abil
ity
0 4 8 12 16 20 24 28 32 36 40 44 48 52
0.75
0.95
1.00
Standard - 4.1 events / 100 pt yrs
Cinacalcet - 0.3 events / 100 pt yrs
0.90
0.85
0.80 Eve
nt-
Fre
e P
rob
abil
ity
Week 0 4 8 12 16 20 24 28 32 36 40 44 48 52
0.75
0.95
1.00
Standard - 6.9 events / 100 pt yrs
Cinacalcet - 3.2 events / 100 pt yrs
0.90
0.85
0.80
P = 0.04
Week
Eve
nt-
Fre
e P
rob
abil
ity
0 4 8 12 16 20 24 28 32 36 40 44 48 52
0.75
0.95
1.00
Standard – 19.7 events / 100 pt yrsCinacalcet – 15.0 events / 100 pt yrs
0.90
0.85
0.80
Week
Eve
nt-
Fre
e P
rob
abil
ity
0 4 8 12 16 20 24 28 32 36 40 44 48 52
0.75
0.95
1.00
Standard – 7.4 deaths / 100 pt yrs
Cinacalcet – 5.2 deaths / 100 pt yrs
0.90
0.85
0.80
P = NS
P = 0.009
P = 0.005
Diet/nutrition, Phosphate Binders, Vitamin D
CaCa
PO4PO4
PTHPTH
Diet/nutrition, Ca-based P-binders Vitamin D
Calcimimetics, Vitamin D
Therapeutic Interventions forManaging Secondary HPT
Adapted from Goodman WG. Nephrol Dial Transplant. 2003;18(suppl 3):iii2-iii8.
• Lab values checked at 1 week:– Phosphorus: 5.4 mg/dL
– Corrected calcium: 8.7 mg/dL
• Patient complains of mild nausea
• Advised to take cinacalcet with evening meal
• No other changes made at this time
Patient Case Update
• Labs rechecked at 1 month– Phosphorus: 5.4 mg/dL
– Corrected calcium: 8.7 mg/dL
– Intact PTH: 290 pg/ml
– Ca x P product: 47
• Nausea resolved
• No further changes warranted at present
Patient Case Update (cont)
Developing a Treatment Algorithm
• Promote patient safety and incorporate strategies for the fewest side effects
• Be consistent with current, valid research and update regularly as new information is available
• Reflect team consensus and consider facility needs or limitations
• Provide a schedule for changes (dose, meds, route of admin)• Provide logical, easy steps• Allow for therapy response time before making additional
changes • Minimize paperwork• Include mechanism to inform patient and team of progress• Define limits and provide mechanism to return management
to MD if treatment outside parameters is needed• Identify outcome measures and provide tracking mechanisms
Therapeutic Options for Secondary HPT: Conclusions
• New phosphate binders offer options for phosphorus reduction without increasing serum calcium
• Vitamin D analogs lower PTH and increase bone mineralization, but also raise calcium and phosphorus
• Cinacalcet can be used to lower PTH despite elevations in calcium and/or phosphorus
• Dialysis is a critical tool for managing ESRD
• Parathyroidectomy can be useful for lowering PTH when pharmacologic intervention fails