mineral metabolism in esrd - institute of kidney...

Mineral Metabolism in ESRDMineral Metabolism in ESRD

Dr. Gordon WongDr. Gordon WongThe Credit Valley Hospital The Credit Valley Hospital May 12, 2007May 12, 2007

THE GOOD, THE BAD AND THE

As Kidney Function Declines, As Kidney Function Declines, Secondary HPT DevelopsSecondary HPT Develops

0

5.5

11

18

22

100+

90–9

980

–89

70–7

960

–69

50–5

940

–49

30–3

920

–29

10–1

9

CrCl (mL/min)

pmol

/L0.5

0.75

1.0

1.25

1.5

100+

90–9

980

–89

70–7

960

–69

50–5

940

–49

30–3

920

–29

10–1

9

CrCl (mL/min)

mm

ol/L

Ionized Calcium

Martinez I et al. Martinez I et al. Am J Kidney Am J Kidney DisDis 1997;29:4961997;29:496--502.502.

iPTH

*

**

*p<0.05, compared to CrCl ≥ 50 mL/min

Phosphorus

CaP

PTH

1,25-OH Vit D3

Renal insufficiency:Renal insufficiency:

P excretion

Ca absorptionPO4 absorption

PathophysiologyPathophysiology of Secondary HPT in CKDof Secondary HPT in CKD

Ca2+

PO43-

KidneyDisease

PTH

SystemicToxicity

BoneDisease

PTH

Vit. D

Adapted from Skorecki K et al. In: Harrison’s Principles of Internal Medicine. 15th ed. 2002:1551-1562.

Renal Bone Disease: Histology Peritoneal Dialysis Renal Bone Disease: Histology Peritoneal Dialysis

PatientsPatients (n=142: (n=142: CanadaCanada))

HyperparathyroidismHyperparathyroidismHIGH TURNOVERHIGH TURNOVER

AdynamicAdynamicLOW TURNOVERLOW TURNOVER

OsteomalaciaOsteomalaciaMixedMixed

hyperparathyroidismhyperparathyroidismosteomalaciaosteomalacia

NormalNormal

60%

5%4%

31%

Sherrard DJ et al; Kidney Int 1993;43:436

Renal Bone Disease: Histology Hemodialysis Renal Bone Disease: Histology Hemodialysis

PatientsPatients (n=117:(n=117:CanadaCanada))

HyperparathyroidismHyperparathyroidismHIGH TURNOVERHIGH TURNOVER

AdynamicAdynamicLOW TURNOVERLOW TURNOVER

OsteomalaciaOsteomalaciaMixedMixed

hyperparathyroidismhyperparathyroidismosteomalaciaosteomalacia

NormalNormal

36%

3%11%

50%

Sherrard DJ et al; Kidney Int 1993;43:436

PTH

CalciumPhosphorus

Deposition into Tissues

Calcification

High Bone Turnover

PTH

CalciumPhosphorus

Low Bone Turnover

Possible Effect of Bone Turnover on Extraskeletal Calcification

Slide courtesy of Dr. K. Martin

Vascular CalcificationVascular Calcification

Passive ProcessPassive ProcessAltered mineral metabolism due Altered mineral metabolism due to CRFto CRFA component of generalized soft A component of generalized soft tissue and visceral calcificationtissue and visceral calcificationMedial wall calcificationMedial wall calcificationAmorphous deposition of Amorphous deposition of calcium and phosphoruscalcium and phosphorusCalcium oxalateCalcium oxalate

Active / Regulated ProcessActive / Regulated ProcessRegulated or modulated by Regulated or modulated by genetic factorsgenetic factorsProteins involved in bone and Proteins involved in bone and mineral metabolism are mineral metabolism are expressed in calcified vascular expressed in calcified vascular lesionslesionsBoth Both intimalintimal and medial wall and medial wall calcificationcalcificationOsteocalcinOsteocalcin, matrix GLA protein, , matrix GLA protein, PTHrPPTHrPHydroxyapatiteHydroxyapatiteVSMC may assume VSMC may assume characteristics of characteristics of osteoblastosteoblast--like like cells cells in vitroin vitro

Ketteler, Kidney International (2006) 70, S5–S9.

+

+ + PO4

CBfa1BMP2

ALP

Osteocalcin

Osteonectin

Leptin

Collagen IFibronectin

LDLox

TNF-α

Dexamethasone

Klotho-/-

PTH 7-84

++++

+

++

++

+

+

Vit D3Ca

+Oncostatin

-

Osteoprotegerin

MGPOsteopontin

BMP7Collagen IV

Fetuin

PTHrP PTH 1-34

-- -

-- -

-

-

Inductors (+) and Inhibitors (-) of Vascular Calcifications

pyrophosphate

+

Molecular Mechanisms of Vascular CalcificationMolecular Mechanisms of Vascular CalcificationFour TheoriesFour Theories

Speer MY & Giachelli M. Cardiovascular Pathology 2004;13:63-70.

Vascular Calcification

1. Loss of Inhibition• MGP• OPN• Fetuin-A/α2-HS glycoprotein• Pyrophosphate• Others

2. Induction of Bone Formation• Vascular

osteoblast/chromdrocyte-like cells

3. Circulating nucleational complexes

4. Cell Death

HyperphosphatemiaHypercalcemia

Ca X Pi

Ca/Pi loadedMatrix vesicles

Apoptoticbodies

BisphosphonatesOPGRemodeling bone

•Pi•Lipids•Inflammatory Cytokines•Others

Vascular Calcification is a Regulated ProcessVascular Calcification is a Regulated Process

Adapted from Derici U et al. Semin Dial 2006;19:60–68

Mechanisms of transdifferentiation of vascular smooth muscle cells by uraemic conditions (in vivo and in vitro):

VSMC with osteoblastic phenotypeHydroxyapatite

Calcification activators

Osteoblastic differentiation

Calcificationinhibitors

Apoptosis of vascular smooth muscle cells

(VSMC)

Mineral imbalance

Calcifying cells

Nucleation by hydroxyapatite vesicles

Identifying those at riskIdentifying those at risk

Association Between Serum Phosphorus and AllAssociation Between Serum Phosphorus and All--Cause and Cardiac MortalityCause and Cardiac Mortality

1.67

1.09 1.021.17 1.24

1.551.46

1.241.211.351.29

1.151.071.13

1.00

1.32

0.96

1.151.13

1.59

0.88

00.2

0.40.60.8

11.21.4

1.61.8

<0.8 0.8-1.0 1.0-1.1 1.1-1.3 1.3-1.5 1.5-1.6 1.6-1.8 1.8-2.0 2.0-2.1 2.1-2.3 >=2.3

Serum Phosphorus (mmol/l)

Rel

ativ

e R

isk

of M

orta

lity All Cause Mortality Cardiac Mortality

p<0.

0001

p=0.

11

p=0.

03

p=0.

30

p=0.

85

p=0.

08

p=0.

32

p=0.

11

p<0.

01

p<0.

0001

p=0.

01

p=0.

55

p=0.

35

p=0.

78

p=0.

31

p=0.

17

p=0.

06

p=0.

04

p<0.

01

p<0.

01

DOPPS I data (1996-2000). Model stratified by country, corrected for facility clustering, and adjusted for age, race, gender, years with ESRD, BMI, 14 summary comorbid conditions, dialysate calcium, serum albumin, iPTH, albumin-corrected calcium, vitamin D use, phosphate binder use, and prior parathyroidectomy. n= 14,298.

Ref

eren

ce

**

** *

*

**

(314) (384) (705) (1055) (1478) (1678)(1620) (1601) (1359) (1104) (3000)n =

0.66

1.040.97 1.03

1.11 1.15 1.17

0.58

0.94 0.97

1.14 1.14 1.12

1.361.29

1.22

1.00

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

<=1.9 1.9-2.1 2.1-2.2 2.2-2.4 2.4-2.5 2.5-2.6 2.6-2.7 2.7-2.8 >=2.8

Albumin Corrected Calcium (mmol/l)

Rel

ativ

e R

isk

of M

orta

lity

All-Cause Mortality Cardiac Mortality

Association Between AlbuminAssociation Between Albumin--Corrected Calcium Corrected Calcium and Alland All--Cause and Cardiac MortalityCause and Cardiac Mortality

DOPPS I data (1996-2000). Model stratified by country, corrected for facility clustering, and adjusted for age, race, gender, years with ESRD, BMI, 14 summary comorbid conditions, dialysate calcium, serum iPTH, phosphorus, albumin, vitamin D use, phosphate binder use, and prior parathyroidectomy. n= 12,114.

p<0.

0001

p<0.

01

p=0.

63p=

0.64

p=0.

59

p=0.

71

p=0.

66

p=0.

16

p=0.

07

p=0.

22

p=0.

07

p=0.

35

p=0.

13

p=0.

06

p=0.

05

p=0.

12

Ref

eren

ce

**

*

(639) (1024) (2437) (2804) (1857) (1643) (912) (436) (362)n =

0.941.00 1.01 0.98

1.161.27 1.23

0.95

1.19 1.141.28

1.62 1.621.49

1.00

0.0

0.5

1.0

1.5

2.0

< 40.0 40.0 - 44.9 45.0 - 49.9 50.0 - 54.9 55.0 - 59.9 60.0 - 64.9 65.0 - 69.9 70.0 +

Rel

ativ

e R

isk

of M

orta

lity

All Cause Mortality Cardiovascular Mortality

Association Between CalciumAssociation Between Calcium-- Phosphorus Phosphorus Product and AllProduct and All--Cause and Cardiac MortalityCause and Cardiac Mortality

Calcium-Phosphorus Product (mg2/dl2)

DOPPS I data (1996-2000). Model stratified by country, corrected for facility clustering, and adjusted for age, race, gender, years with ESRD, BMI, 14 summary comorbid conditions, dialysate calcium, serum iPTH, albumin, vitamin D use, phosphate binder use, and prior parathyroidectomy. n=13,940.

(3637) (1710) (1634) (1663) (1368) (1109) (860) (1959)n =

p=0.

27

p=0.

93

Ref

eren

ce

p=0.

79

p=0.

07

p=0.

001

p<0.

001

p=0.

90

p=0.

57

p=0.

08

p=0.

03

p<0.

001

p<0.

001

p<0.

001

p=0.

19

*

*

*

*

*

*

Association Between Intact PTH (Association Between Intact PTH (iPTHiPTH) ) and Alland All--Cause and Cardiac MortalityCause and Cardiac Mortality

iPTH (pmol/l)

DOPPS I data (1996-2000). Model stratified by country, corrected for facility clustering, and adjusted for age, race, gender, years with ESRD, BMI, 14 summary comorbid conditions, dialysate calcium, serum albumin, phosphorus, albumin-corrected calcium, vitamin D use, phosphate binder use, and prior parathyroidectomy. n=8,638.

p=0.

52

p=0.

90

p=0.

22

p=0.

95

p=0.

63

p=0.

35

p=0.

80

p=0.

22

p=0.

80

p=0.

41

p=0.

07

p=0.

01

p=0.

03

p=0.

28

(2845) (1061) (2021) (535) (370) (215) (557)(1034)n =

Ref

eren

ce

Young et al.; Kidney Int; In press

1.04 1.09 1.040.97 0.97

1.28 1.24

1.01 1.011.12

0.83

1.16

1.64

1.19

1.00

0.00.20.40.60.81.01.21.41.61.8

< 11 11-16.5 16.5-33 33-50 50-66 66-82.5 82.5-99 > 99

Rel

ativ

e R

isk

of M

orta

lity

All Cause Mortality Cardiovascular Mortality

KDOQI KDOQI vsvs CSN Target RangesCSN Target Ranges

10 10 –– 505016.5 16.5 –– 3333150 150 –– 300300iPTHiPTH

2.05 2.05 –– 2.542.542.10 2.10 –– 2.372.378.4 8.4 –– 9.59.5CalciumCalcium

0.81 0.81 –– 1.421.421.13 1.13 –– 1.781.783.5 3.5 –– 5.55.5PhosphatePhosphate

SI units SI units ((mmolmmol/L)/L)

SI units SI units ((mmolmmol/L)/L)

Conventional units Conventional units (mg/(mg/dLdL))

CSN 2006CSN 2006KDOQIKDOQI

CSN targets might lead to worse Canadian performance compared to KDOQI.

Number of Mineral Metabolism Target Number of Mineral Metabolism Target Levels Achieved, by CountryLevels Achieved, by Country

Patients (%) within targets

Country

DOPPS II data (2002-04), among prevalent cross-section of patients with reported values for all four measures, n=4687

# TargetsAchieved

4

3

2

1

022 12 13 19 15 12 16 21 22 25 17

2424 19

28 28 23 2225 27 28

24

2835 40

28 29 32 2833 32 30

30

22 21 22 20 22 26 2817 23

8 7 7 7 6 718 14

4 4 2 35

0

20

40

60

80

100

Australia-New

Zealand

BelgiumCanadaFranceGermany Italy Japan Spain Sweden UK US

Projected Number of PatientProjected Number of Patient--years Saved for all Hemodialysis years Saved for all Hemodialysis Patients Who Attained the Best Targets According to the Patients Who Attained the Best Targets According to the Guidelines Practiced in Canada: Projected for the Next 5 Guidelines Practiced in Canada: Projected for the Next 5

years (2006years (2006--2010)2010)

13,49213,4923,43,4

((15.7%15.7%))4,3574,357((5.1%5.1%))

8,3028,302((9.6%9.6%))

920920((1.1%1.1%))

1,0261,026((1.2%1.2%))

1,5961,596((1.9%1.9%))

401401((0.5%0.5%))

--Patient years Patient years gained if 100% gained if 100% within targets (% within targets (% of total years)of total years)55

99,63799,63790,50190,50194,44694,44687,06487,06487,17187,17187,74087,74086,54586,54586,14486,144Patient years Patient years (total)(total)

0.1010.1010.1520.1520.1290.1290.1740.1740.1730.1730.1700.1700.1770.1770.1800.180Annual death rate Annual death rate (per patient year)(per patient year)

TotalTotal11(sum of 1(sum of 1--6)6)

66Facility Facility cathetecatheter ≤r ≤10%10%

55AlbumAlbum

in in ≥≥40 40 g/Lg/L

44CalciumCalcium2.22.2--2.6 2.6 mmol/Lmmol/L

33POPO44

0.80.8--1.8 1.8

mmol/Lmmol/L

22HbHb≥≥110 110 g/Lg/L

11Kt/VKt/V≥≥1.21.2

CurreCurrent nt

statiststatisticsics

MeasureMeasure

Nephrology News and Issues (NN&I) (21:5:69-85, 2007).

TreatmentTreatment

Treatment overview:Treatment overview:

dietary POdietary PO44 restrictionrestrictionPOPO44 removal via dialysisremoval via dialysisPOPO44 bindersbindersvitamin D supplementationvitamin D supplementationcalcimimeticscalcimimetics

Treatment:Treatment:

dietary protein intake of 1 dietary protein intake of 1 -- 1.2 g/kg/day 1.2 g/kg/day results in a P load of ~ 1 g/day or ~ 7 g/wk results in a P load of ~ 1 g/day or ~ 7 g/wk of which 60% is actually absorbed ~ 4 g/wkof which 60% is actually absorbed ~ 4 g/wkHD will remove ~ 3 g/wkHD will remove ~ 3 g/wkPD will remove ~ 2 g/wkPD will remove ~ 2 g/wkPOPO44 binders are critical in managementbinders are critical in management

Treatment: phosphate bindersTreatment: phosphate binders

costcostlimited efficacylimited efficacy

nonnon--Ca, nonCa, non--AlAleffect on effect on dyslipidemiadyslipidemiareduced vascular reduced vascular calcificationcalcification

sevelamersevelamer((RenagelRenagel))

Build up ?significanceBuild up ?significancenonnon--Ca, nonCa, non--AlAlpotetncypotetncy

lanthanum lanthanum carbonatecarbonate((FosrenolFosrenol))

DisadvantagesDisadvantagesAdvantagesAdvantages

Al related toxicityAl related toxicityefficacyefficacyAlOHAlOH

hypercalcemiahypercalcemiacalcification riskcalcification risk

costcostCaCOCaCO33

SevelamerSevelamer

SevelamerSevelamer: effect on coronary : effect on coronary calcificationcalcification

129 pts new to 129 pts new to hemodialysishemodialysissevelamer vs sevelamer vs Ca containing P binderCa containing P binderEBCT baseline, 6 months, 12 months, EBCT baseline, 6 months, 12 months, 18 months18 months*** at baseline 37% of *** at baseline 37% of sevelamer sevelamer treated pts had no detectable coronary treated pts had no detectable coronary lesions lesions vs vs 31% in Ca group (no 31% in Ca group (no comment as to statistical significance)comment as to statistical significance)

Block, Kidney International, Vol. 68 (2005), pp. 1815–1824

Block G, Kidney International (2007) 71, 438–441.

DCOR(Dialysis Clinical DCOR(Dialysis Clinical OutcomesRevisitedOutcomesRevisited):):

2100 HD pts2100 HD ptsopen label open label sevelamer vs sevelamer vs Ca based bindersCa based bindersf/u 45 monthsf/u 45 monthsprimary endpoint: all cause mortalityprimary endpoint: all cause mortality

Suki W, et al. Renal Week 2005; November 8-13, 2005; Philadelphia, PA. Abstract TH-PO745.

Suki W, et al. Renal Week 2005; November 8-13, 2005; Philadelphia, PA. Abstract TH-PO745.

16.1516.1515.0215.02Mortality incidence Mortality incidence rate (per 100 rate (per 100 patientpatient--years)years)

274 (27) 274 (27)

Calcium Calcium bindersbinders

0.91 (0.770.91 (0.77––1.08)1.08)

Relative risk Relative risk (95%)(95%)

265 (26) 265 (26) SevelamerSevelamer

Deaths, n (%)Deaths, n (%)End point End point

DCOR: Primary end point (all-cause mortality)

Lanthanum CarbonateLanthanum Carbonate

Lanthanum carbonateLanthanum carbonate is a high affinity phosphate is a high affinity phosphate binder binder in vivoin vivo

Adapted from: Damment SJP, Webster I. Poster presented at ASN 2003Hutchison A. Nephrol Dial Transplant 2004;19 Suppl 1:i19–24

Time on treatment (weeks)

Urin

e ph

osph

orus

exc

retio

n(m

mol

/24

h)

0

0.3

0.4

0.5

0.6

0.8

–3 –2 –1 0 1 2 6

0.1

0.2

3 4 5

0.7 5/6th nephrectomized rat model

Vehicle

CaCO3

AIOH3

Lanthanum carbonate

Sevelamer HCL

Adverse events versus standard therapyAdverse events versus standard therapyPercentage of patients with adverse eventPercentage of patients with adverse eventAdverse eventAdverse event

19192121Chest painChest pain

24242323DyspnoeaDyspnoea

20202121MyalgiaMyalgia

20202121DizzinessDizziness

21212121Dialysis graft occlusionDialysis graft occlusion

20201616Oedema, peripheralOedema, peripheral

20202020CoughingCoughing

24242424DiarrhoeaDiarrhoea

21212222HeadacheHeadache

24242525Dialysis graft Dialysis graft complicationcomplication

22222727VomitingVomiting

29293737NauseaNausea

Standard therapy Standard therapy (adjusted rates) (adjusted rates)

((nn = 677)= 677)

FosrenolFosrenol®®((nn = 682)= 682)

Finn WF et al. Clin Nephrol 2006;65:191–202

Contrasting metabolismContrasting metabolism

Faecal excretion Faecal excretion

Kidneys not involved in excretion

no increased risk for deposition in ESRD

Biliary elimination

Negligible biliary elimination

GI absorption.0.01-0.1%

Al-contaminated dialysate

ESRD: urinary excretion blocked

increased risk for deposition

GI absorption<0.002%

p.o.p.o.

lanthanumlanthanum

carbonate

carbonateMarginal lanthanum

intake through breathing and food

p.o.

aluminium

hydroxideSignificant aluminium

intake through breathing and food

GI absorption of Al increased by citrate, PTH, uremic state, ...

GI absorption of La not increased by citrate.P binding not influenced by pH

LanthanumAluminium

Adapted from: Behets GJ et al. Curr Opin Nephrol Hypertens 2004;13:403–9Persy VP et al. Semin Dial 2006;19:195–9

Altmann, Kidney International (2007) 71, 252–259.

Vitamin DVitamin D

Vitamin D Deficiency is Prevalent Vitamin D Deficiency is Prevalent in CKD Patientsin CKD Patients

14

42

42

2

Normal Vitamin D (> 30 ng/mL)Vitamin D Insufficiency (16-30 ng/mL)Mild Vitamin D Deficiency (5-15 ng/mL)Severe Vitamin D Deficiency (<5 ng/mL)

3

17

66

14

Gonzales EA et al. Am J Nephrol 2004;24:503-510.

N=43 patients with SCr 1 and 5 mg/dL (calculated GFR 11-111 ml/min)

N=103 patients undergoing chronic HD

Percent of Patients

Percent of Patients

Shoji, Nephrol Dial Transplant (2004) 19: 179–184

Teng, N Engl J Med 2003;349:446-56.

Teng, N Engl J Med 2003;349:446-56.

calcitriol

paricalcitol

Teng, N Engl J Med 2003;349:446-56.

paricalcitol

calcitriol

Tentori, KI 2006, 70, 1858–1865.

No vitamin D vs. Any vitamin D

Tentori, KI 2006, 70, 1858–1865.

CinacalcetCinacalcet

Red

uctio

n Fr

om B

asel

ine

(%)

0

10

20

30

40

50 US/Can Phase 3 EU/Aus Phase 3 US/Can/Aus Phase 3

38%

13%

48%

17%

40%

13%

7%6%10%

8% 7%7%

iPTH Ca x P PCa iPTH Ca x P PCa iPTH Ca x P PCa

Sensipar™ Product Monograph

SensiparSensipar™ Consistently Improved All ™ Consistently Improved All Secondary HPT Endpoints in Phase III TrialsSecondary HPT Endpoints in Phase III Trials

*TARGETS: iPTH 150 - 300 pg/mL (16.5 - 33 pmol/L), Ca x P < 55 mg2/dL2 (< 4.5 mmol2/L2), Ca 8.4–9.5 mg/dL (2.1-2.4 mmol/L), P 3.5–5.5 mg/dL (1.1-1.8 mmol/L)

Clinical Outcomes with Clinical Outcomes with CinacalcetCinacalcet::

Combined analysis of safety dataCombined analysis of safety dataParathyroidectomyParathyroidectomy, fracture, hospitalisations and , fracture, hospitalisations and mortalitymortality

Methods:Methods:Database: 1184 patients (697 Database: 1184 patients (697 cinacalcetcinacalcet, 487 control), 487 control)4 similarly designed randomised, double4 similarly designed randomised, double--blind, blind, placeboplacebo--controlled clinical trialscontrolled clinical trialsCinacalcetCinacalcet or placebo administered to patients or placebo administered to patients receiving standard care (phosphate binders and receiving standard care (phosphate binders and vitamin D) for SHPT vitamin D) for SHPT Relative risk assessment with followRelative risk assessment with follow--up times from 6 up times from 6 to 12 monthsto 12 months

Adapted from Cunningham J et al. Kidney Int 2005

Reduction in the Risk of Reduction in the Risk of ParathyroidectomyParathyroidectomy with with

CinacalcetCinacalcet

* Refers to the risk that an event does not occur Adapted from Cunningham J et al. Kidney Int 2005

Standard therapyStandard therapy + cinacalcet

Week

Even

t-fre

e Pr

obab

ility

*

0 4 8 12 16 20 24 28 32 36 40 44 48 52

0.90

0.95

1.00

93% RRR

p < 0.009

0.3 (cinacalcet) vs. 4.1 (control) parathyroidectomies per 100 patient years (p < 0.01)

Reduced Risk of Fracture with Reduced Risk of Fracture with CinacalcetCinacalcet


Week

Even

t-fre

e Pr

obab

ility

*

0.90

0.95

1.00

4 8 12 16 20 24 28 32 36 40 44 48 520


54% RRR

p < 0.04

Patients treated with cinacalcet had a significant reduction in fracture rate compared to control - 3.2 vs. 6.9 fractures per 100 patient years (p < 0.05)

Reduced CV Reduced CV HospitalizationHospitalizationRates with Rates with CinacalcetCinacalcet


Week

Even

t-fre

e Pr

obab

ility

*

0.75

0.80

0.85

0.90

0.95

1.00

0 4 8 12 16 20 24 28 32 36 40 44 48 52

39% RRR

p < 0.005


Patients treated with cinacalcet had a significant reduction in CV hospitalization rates compared to control – 15.0 vs. 19.7 hospitalizations per 100 patient years (p < 0.01)

Reduction

Slight Reduction

No effect

Increase

iPTHiPTH

Non CaNon Ca--based based POPO44 bindersbinders

CaCa--basedbasedPOPO44 bindersbinders

CinacalcetCinacalcet HClHCl

Vitamin DVitamin D

Ca Ca xx PPCaCaPPAgentAgent

Effects of Drug Therapies on Effects of Drug Therapies on Bone/Mineral ParametersBone/Mineral Parameters

Summary:Summary:

CVD is the major cause of mortality in CVD is the major cause of mortality in ESRDESRD

vascular calcification is largely attributable vascular calcification is largely attributable to disordered mineral metabolismto disordered mineral metabolism

therapeutic strategies are evolvingtherapeutic strategies are evolving

THE GOOD, THE BAD AND THE UGLY

mineral metabolism in esrd - institute of kidney...

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