Sandro MazzaferroCattedra di Nefrologia

I Facoltà Medicina e Chirurgia“Sapienza” Università di Roma

XV Riunione del GdS DDialisi PeritonealeBari, 19-20 Febbraio 2010

Question Time 2:

In DP più vantaggi con la vitamina D o i VDRAs?

Why active Vitamin D therapy in PD

• To suppress PTH:– But serum Ca Increases (also Ca balance) – But serum P Increases (also P balance)

• To improve morbidity/mortality:– Linked to SH (bone disease/fractures and toxicity)– Linked to CV effects of CKD-MBD

Bushinsky CJASN 2010

Structures of Calcitriol and Paricalcitol

HO OH OH

CH3

CH2

H3COH

CH3

CH3 H3COH

CH3

CH3

HO

Calcitriol19-nor-1-a, 25-dihydroxyvitamin D21-a, 25-dihydroxyvitamin D3

Paricalcitol

InduzioneVDR

Intestino

Ca e P da Osso

+

+

_

_

6.00

5.50

5.00

4.50

4.00

UREMIC0N 2 4 8 8 25 75 ng

Ioni

zed

Calc

ium

(mg/

dL)

* = p<0.02

1.25-(OH)2D3 19-nor-1,25(OH)2D2

*

The Effects of 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 on Ionized Calcium in Uremic Rats

Slatopolsky AJKD 1995

Effects of 1,25D-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on Intestinal 1,25-(OH)2D3–VDR Binding in Uremic Rats

0

50

100

150

200

NormalUremic

0 2 6 25 100 ng1,25-(OH)2D3 19-nor-1,25-(OH)2D2

*p<0.01 vs Uremic+1,25D-6ng

* * *

3 H-1

,25-

(OH

) 2D3 S

pec

ific

Bin

din

g

(fm

ol/m

g p

rote

i n)

Slatopolsky AJKD 1995

10-11

Concentration, M

0

20

40

60

80

100

120

Area

Res

orbe

d, %

108

1,25

D3

1,25D3

19-norD2

Dose-dependent Effects of 1,25D3 and 19-norD2 on Osteoclastic Resorption: Area Resorbed

10-10 10-9 10-8 10-7 10-6

Holliday S, JASN 11:1857, 2000

1011

Concentration, M

0

20

40

60

80

100

120

Num

ber o

f Pits

, % 1

0-8 1

,25D

3

1,25D3

19-norD2

Dose-dependent Effects of 1,25D3 and 19-norD2

on Osteoclastic Resorption: Number of Pits

1010 109 108 107 106

Holliday S, JASN 11:1857, 2000

Serum Calcium and Phosphorus in Placebo and Paricalcitol Treated Patients

Weeks

1 2 3 4 5 6 7 8 9 10 11 12

Seru

m C

alci

um o

r Pho

spho

rus

mg/

dl

0

1

2

3

4

5

6

7

8

9

10

11

ParicalcitolPlacebo

Calcium

Phosphorus

Martin et al. JASN 9: 1427, 1998

Lund et al Am J Neph, 2010Intestinal Ca Absorption in HD: comparison between Calcitriol and

Paricalcitol

22 HD pts; PTH>200pg/ml

Calcitriol i.v.; 2ug/HDx6

Paricalcitol i.v.; 6 ug/HDx6

Potential advantages of Paricalcitol vs Calcitriol

• PTH suppression with:– Lower calcemic effect;– Lower phosphate effect;– Better survival

To date no RCT is available to clearly demonstrate the last statement.

Sanchez NDT 2004 Low vs standard CaD in PD

Not all ABD!

CaD = 1,75 M

CaD = 1,25 M

1 Year!

PTH

OC

Mg

No chan

ge!!

P

Ca++

TCa