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Reduced VDR activation in CKD

ESPERIENZA CLINICA SULL'USO DEL PARACALCITOLO ORALE NEI PAZIENTI CON IRC STADIO 3-5 IN TERAPIA CONSERVATIVA S. Di Stante, H. Kulurianu , F. Manenti , M. Marani , M. Martello, M. Di Luca UOC Nefrologia e Dialisi AO Ospedali Riuniti Marche Nord P.O Ospedaliero “S. Salvatore” Pesaro.

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Reduced VDR activation in CKD

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  1. ESPERIENZA CLINICA SULL'USO DEL PARACALCITOLO ORALE NEI PAZIENTI CON IRC STADIO 3-5 IN TERAPIA CONSERVATIVA S. Di Stante, H. Kulurianu, F. Manenti, M. Marani, M. Martello, M. Di Luca UOC Nefrologia e Dialisi AO Ospedali Riuniti Marche Nord P.O Ospedaliero “S. Salvatore” Pesaro

  2. Reduced VDR activation in CKD • Progressive • loss of renal 1-alfa hydroxylase with the reductions in functional • renal mass. • Reduction of the amount of filtered 25(OH)D • Defective renal 25(OH)D uptake by reduced renal megalin content • Defective uptake of 25(OH) D by monocytes–macrophages. • Inhibition of remnant 1-alfa hydroxylase activity by elevations in serum levels of: • uremic toxins, • PTH fragments • FGF-23 Dusso A. et al .Vitamin D in chronic kidney disease. Best Practice & Res Clin Endocrinology & Metabolism 25 (2011) 647–655

  3. 80 % 20 %

  4. Effect of vitamin D supplementation on PTH levels in CKD 2-4 stages among RCT 264 pts examined in RCT Baseline 25(OH)D levels ranged from 8.5 to 24.5 ng/ml. Significant increase in serum 25(OH)D was associated with significant decline in PTH levels. RCTs showed a net decrease of 31 pg/ml in PTH levels . No significant increase in hypercalcemia and hyperphosphatemia Kandula P et al. Clin J Am Soc Nephrol 2011;6:50-62

  5. Paricalcitol decrease iPTH levels with a trend towards hypercalcemia , although not statistically significant, and no hyperphosphatemia PTH target Ca target P target

  6. Aimof the study Analisi retrospettiva della nostra esperienza con Paracalcitolo orale per 12 mesi in 34 pazienti con IRC stadio 3-5, IPTH secondario, deficit/carenza di 25OHD, calcemia e fosforemia nei limiti di normalità, non precedentemente trattati con vitamina D nativa e/o attiva, né chelanti del fosforo. * valori espressi come mediana

  7. p=0.002 iPTH Popolazione in toto p=0.01 800 p<0.01 600 iPTH (pg/ml) 400 200 Valori espressi come mediana e range interquartile 0 NS T0 T3 T6 T9 T12

  8. Calcio - Fosforo Popolazione in toto NS Valori espressi come media

  9. Paracalcitolo vs Parametri MBD Confronto stadi CKD

  10. Pazienti a target Tutti i parametri MBD P<0.05

  11. # * * p<0.02 T0 vs T12 e T3 vs T12 # p<0.02 T0 vs T12 iPTH e Vit D PCT PTH 25OH Vit D $ @ @ $ ° ° p<0.05 T0 vs T12 @ p<0.02 $ p=0.01

  12. Calcio - Fosforo NS @# @ p<0.02 T0 vs T9 # p=0.02 T3 vs T9 Valori espressi come media

  13. Conclusioni • I risultati dello studio confermano l’efficacia del PCT nel controllo del iPTH in pazienti in terapia conservativa negli stadi 3-5 della IRC senza incidenza di ipercalcemia e iperfosforemia. • La correzione del deficit di 25OHD ha consentito di ottenere il controllo del iPTH a parità di dose di PCT nei due gruppi di pazienti con diverso grado di Iperparatiroidismo.

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