1. In DP più vantaggi con la vitamina D o i VDRAs?
XV Riunione del GdS DDialisi Peritoneale
Bari, 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

2. 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

3. Bushinsky CJASN 2010

4. Structures of Calcitriol and Paricalcitol
CH3
H3C
CH3
H3C
CH3 OH OH
CH3
CH3
Induzione
VDR
Intestino _ +
CH2
Ca e P
da Osso _ + HO OH HO OH
1-a, 25-dihydroxyvitamin D3
19-nor-1-a, 25-dihydroxyvitamin D2
Calcitriol
Paricalcitol

5. The Effects of 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 on Ionized Calcium in Uremic Rats
6.00
* = p<0.02
5.50 *
5.00
Ionized Calcium (mg/dL)
4.50
4.00
UREMIC N 2 4 8 8 25 75 ng
1.25-(OH)2D3
19-nor-1,25(OH)2D2
Slatopolsky AJKD 1995

6. Effects of 1,25D-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on Intestinal 1,25-(OH)2D3–VDR Binding in Uremic Rats
*p<0.01 vs Uremic+1,25D-6ng
(fmol/mg protein)
3H-1,25-(OH)2D3 Specific Binding * * *
Uremic 2 6 25
100 ng
Normal
1,25-(OH)2D3
19-nor-1,25-(OH)2D2
Slatopolsky AJKD 1995

7. Dose-dependent Effects of 1,25D3 and 19-norD2 on Osteoclastic Resorption: Area Resorbed
120
1,25D3
100
19-norD2 80
Area Resorbed, % 108 1,25D3 60 40 20
10-11
10-10
10-9
10-8
10-7
10-6
Concentration, M
Holliday S, JASN 11:1857, 2000

8. Dose-dependent Effects of 1,25D3 and 19-norD2 on Osteoclastic Resorption: Number of Pits
120
1,25D3
100
19-norD2 80
Number of Pits, % ,25D3 60 40 20
1011
1010
109
108
107
106
Holliday S, JASN 11:1857, 2000
Concentration, M

9. Serum Calcium and Phosphorus in Placebo and Paricalcitol Treated Patients11 10
Calcium 9 8 7 6
Phosphorus
Serum Calcium or Phosphorus mg/dl 5 4 3 2 1 1 2 3 4 5 6 7 8 9 10 11 12
Weeks
Martin et al. JASN 9: 1427, 1998

12. 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

13. 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.

14. Sanchez NDT 2004 Low vs standard CaD in PD
Not all ABD!
CaD = 1,75 M
CaD = 1,25 M
1 Year!

15. PTH
TCa OC
No change!!
Ca++ Mg P