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

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Presentation transcript:

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

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

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

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

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, % 10-8 1,25D3 60 40 20 1011 1010 109 108 107 106 Holliday S, JASN 11:1857, 2000 Concentration, M

Serum Calcium and Phosphorus in Placebo and Paricalcitol Treated Patients 11 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

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 Not all ABD! CaD = 1,75 M CaD = 1,25 M 1 Year!

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