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
4.00UREMIC
0N 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
peci
fic B
indi
ng
(fm
o l/ m
g pr
o te i
n )
Slatopolsky AJKD 1995
10-11
Concentration, M
0
20
40
60
80
100
120
Area
Res
orbe
d, %
108
1,25
D 3
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
Weeks1 2 3 4 5 6 7 8 9 10 11 12
Seru
m C
alci
um o
r Pho
spho
rus m
g/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