reduced vdr activation in ckd
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/1.jpg)
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
![Page 2: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/2.jpg)
Reduced VDR activation in CKD
•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.
Progressiveloss of renal 1-alfa hydroxylase with the reductions in functionalrenal mass.
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
![Page 3: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/3.jpg)
20 % 80 %
![Page 4: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/4.jpg)
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
![Page 5: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/5.jpg)
Paricalcitol decrease iPTH levels with a trend towards hypercalcemia , although not statistically significant, and no hyperphosphatemia
PTH target
Ca target
P target
![Page 6: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/6.jpg)
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.
Parametri Tot Vit D 20-30 Vit D < 20 p
N. pazienti 34 17 17 NS
Sesso (M/F) 22/12 13/4 9/8 NS
Età (anni ± DS) 71.1±16.3 66.1± 18.7 76 ± 12.1 NS
GFR (ml/min ± DS) Stadio 3 36.7 ± 6.8 36 ± 5.3 37.5 ± 8.7 NS
Stadio 4 24 ± 6.5 24 ± 6 23.8 ± 7.4 NS
Stadio 5 10.5 ± 1.3 11 ± 1.4 10 ± 1.4 NS
iPTH (pg/ml)* 196.5 183.5 306.5 0.01
Ca (mg/dl ± DS) 9.2 ± 0.3 9.2 ± 0 9.2 ± 0.4 NS
P (mg/dl ± DS) 3.8 ± 1 3.7 ± 1.1 3.9 ± 0.9 NS
25-OHD (ng/ml ± DS) 20.7 ± 12 25.6 ± 9.9 16.7 ± 6.7
ALP (UI/l ± DS) 84.7 ± 28 94.2 ± 27.4 76.8 ± 23.4 NS
PCR 0.4 ± 0.3 0.7 ± 0 0.3 ± 0.2 NS
Paracalcitolo (mcg/sett ± DS) 6.2 ± 2.9 6.3 ± 2.7 6 ± 3.2 NS
Vit D (UI/sett ± DS) - - 4933 ± 896 -
* valori espressi come mediana
![Page 7: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/7.jpg)
Valori espressi come mediana e range interquartile
Popolazione in toto
iPT
H (
pg/m
l)
T12T9T6T3T0
800
400
200
0
p<0.01
p=0.002
p=0.01
600
NS
![Page 8: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/8.jpg)
Valori espressi come media
Popolazione in toto
NS
![Page 9: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/9.jpg)
Confronto stadi CKDStadio 3
6,3 6,65,9 5,5
6,4
0
50
100
150
200
250
T0 T3 T6 T9 T12
Tempo (mesi)
iPT
H (
pg
/ml)
0
2
4
6
8
10
12
14
16
18
20
PC
T (
mcg
/sett
), C
a e
P (
mg
/dl)
PCT PTH Ca P
Stadio 4
6,1 5,8 6,15,4 5,4
0
50
100
150
200
250
T0 T3 T6 T9 T12
Tempo (mesi)
iPT
H (
pg
/ml)
0
2
4
6
8
10
12
14
16
18
20
PC
T (
mcg
/sett
), C
a e
P (
mg
/dl)
Stadio 5
6,0 6,06,8
4,33,3
0
50
100
150
200
250
300
350
400
450
500
T0 T3 T6 T9 T12
Tempo (mesi)
iPT
H (
pg
/ml)
0
2
4
6
8
10
12
14
16
18
20
PC
T (
mcg
/sett
), C
a e
P (
mg
/dl)
![Page 10: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/10.jpg)
Tutti i parametri MBD
P<0.05
![Page 11: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/11.jpg)
°
° p<0.05 T0 vs T12
PTH 25OH
PCT Vit D
@
*
* p<0.02 T0 vs T12 e T3 vs T12
# p<0.02 T0 vs T12
#@
@ p<0.02
$ p=0.01
$
$
![Page 12: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/12.jpg)
Valori espressi come media
@ p<0.02 T0 vs T9
# p=0.02 T3 vs T9
@ #
NS
![Page 13: Reduced VDR activation in CKD](https://reader036.vdocuments.mx/reader036/viewer/2022081516/56813121550346895d9792c9/html5/thumbnails/13.jpg)
• 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.