Autosomal-dominant polycystic kidney disease: tolvaptan use in adolescents and young adults with rapid progression.
Adolescent
Antidiuretic Hormone Receptor Antagonists
/ pharmacology
Disease Progression
Female
Glomerular Filtration Rate
/ drug effects
Humans
Kidney
/ drug effects
Liver
/ drug effects
Male
Polycystic Kidney, Autosomal Dominant
/ genetics
Prospective Studies
Risk
Tolvaptan
/ pharmacology
Treatment Outcome
Young Adult
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
17
12
2019
accepted:
09
04
2020
revised:
07
04
2020
pubmed:
12
5
2020
medline:
15
1
2022
entrez:
12
5
2020
Statut:
ppublish
Résumé
The phase 3 Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO 3:4) clinical trial demonstrated the beneficial effect of tolvaptan on kidney growth and function in subjects aged 18-50 years over a 3-year period. However, it did not specifically assess the use of tolvaptan in adolescents and young adults (AYAs) with ADPKD. A post hoc analysis of the TEMPO 3:4 trials was performed for patients aged 18-24 years. The primary outcome was the annual rate of change in total kidney volume (TKV). The secondary outcome was to evaluate long-term safety of tolvaptan using Hy's law of hepatotoxicity. A total of 51 patients in the 18-24 age group were analyzed (tolvaptan: 29, placebo: 22). The tolvaptan group had a lower mean percentage of TKV growth per year compared to the placebo group (3.9% vs. 6.5%, P = 0.0491). For secondary outcomes, 63 patients in the AYA subgroup were evaluated. In both the AYA and adult groups, none of the patients met the criteria for Hy's law of hepatotoxicity. This post hoc analysis suggests that tolvaptan, with appropriate patient selection and management, can provide effective and acceptably safe treatment in AYAs with ADPKD. Tolvaptan slows the increase in total kidney volume in patients aged 18-24 years with ADPKD. Tolvaptan posed no risk of potential liver injury measured via Hy's law of hepatotoxicity in the AYA stratum. This study suggests that tolvaptan has beneficial outcomes in AYAs. This post hoc analysis suggests the need for additional studies with a larger pediatric patient population. The impact is significant as tolvaptan had not been specifically examined in the AYA patient population previously.
Sections du résumé
BACKGROUND
The phase 3 Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO 3:4) clinical trial demonstrated the beneficial effect of tolvaptan on kidney growth and function in subjects aged 18-50 years over a 3-year period. However, it did not specifically assess the use of tolvaptan in adolescents and young adults (AYAs) with ADPKD.
METHODS
A post hoc analysis of the TEMPO 3:4 trials was performed for patients aged 18-24 years. The primary outcome was the annual rate of change in total kidney volume (TKV). The secondary outcome was to evaluate long-term safety of tolvaptan using Hy's law of hepatotoxicity.
RESULTS
A total of 51 patients in the 18-24 age group were analyzed (tolvaptan: 29, placebo: 22). The tolvaptan group had a lower mean percentage of TKV growth per year compared to the placebo group (3.9% vs. 6.5%, P = 0.0491). For secondary outcomes, 63 patients in the AYA subgroup were evaluated. In both the AYA and adult groups, none of the patients met the criteria for Hy's law of hepatotoxicity.
CONCLUSIONS
This post hoc analysis suggests that tolvaptan, with appropriate patient selection and management, can provide effective and acceptably safe treatment in AYAs with ADPKD.
IMPACT
Tolvaptan slows the increase in total kidney volume in patients aged 18-24 years with ADPKD. Tolvaptan posed no risk of potential liver injury measured via Hy's law of hepatotoxicity in the AYA stratum. This study suggests that tolvaptan has beneficial outcomes in AYAs. This post hoc analysis suggests the need for additional studies with a larger pediatric patient population. The impact is significant as tolvaptan had not been specifically examined in the AYA patient population previously.
Identifiants
pubmed: 32392574
doi: 10.1038/s41390-020-0942-2
pii: 10.1038/s41390-020-0942-2
doi:
Substances chimiques
Antidiuretic Hormone Receptor Antagonists
0
Tolvaptan
21G72T1950
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
894-899Références
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