XV Riunione del GdS DDialisi Peritoneale
Bari, 19-20 Febbraio 2010
Question Time 2:
In DP più vantaggi con la vitamina D
o i VDRAs?
Sandro Mazzaferro
Cattedra di Nefrologia
I Facoltà Medicina e Chirurgia
“Sapienza” Università di Roma
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
CH3
H3C
H3C
CH3
OH
CH3
OH
CH3
+
Induzione
VDR
Intestino
CH2
+
HO
Ca e P
da Osso
OH
1-a, 25-dihydroxyvitamin D3
Calcitriol
CH3
_
_
HO
OH
19-nor-1-a, 25-dihydroxyvitamin D2
Paricalcitol
The Effects of 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2
on Ionized Calcium in Uremic Rats
6.00
Ionized Calcium (mg/dL)
* = p<0.02
5.50
*
5.00
4.50
4.00
N
0
2
UREMIC
4
8
1.25-(OH)2D3
8
25
75
ng
19-nor-1,25(OH)2D2
Slatopolsky AJKD 1995
Specific Binding
2D3
3H-1,25-(OH)
Effects of 1,25D-(OH)2D3 and 19-Nor-1,25-(OH)2D2
on Intestinal 1,25-(OH)2D3–VDR Binding in Uremic
Rats
200
*p<0.01 vs Uremic+1,25D-6ng
150
100
*
*
*
50
0
Uremic
Normal
Slatopolsky AJKD 1995
0
2
6
1,25-(OH)2D3
25
100 ng
19-nor-1,25-(OH)2D2
Dose-dependent Effects of 1,25D3 and 19-norD2 on
Osteoclastic Resorption: Area Resorbed
120
1,25D3
Area Resorbed, % 108 1,25D3
100
19-norD2
80
60
40
20
0
10-11
Holliday S, JASN 11:1857, 2000
10-10
10-9
10-8
Concentration, M
10-7
10-6
Dose-dependent Effects of 1,25D3 and 19-norD2
on Osteoclastic Resorption: Number of Pits
120
Number of Pits, % 10-8 1,25D3
1,25D3
100
19-norD2
80
60
40
20
0
1011
1010
Holliday S, JASN 11:1857, 2000
109
108
Concentration, M
107
106
Serum Calcium and Phosphorus in Placebo and
Paricalcitol Treated Patients
Placebo
Paricalcitol
11
Serum Calcium or Phosphorus mg/dl
10
Calcium
9
8
7
6
Phosphorus
5
4
3
2
1
0
1
2
3
4
5
6
7
8
9
10
11
12
Weeks
Martin et al. JASN 9: 1427, 1998
Lund et al Am J Neph, 2010
Intestinal 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
1 Year!
PTH
TCa
OC
Mg
Ca++
P