Targeting Calcineurin Inhibitor-Induced Arterial Hypertension in Liver Transplanted Children Using Hydrochlorothiazide.
J Pediatr Pharmacol Ther
; 27(5): 428-435, 2022.
Article
en En
| MEDLINE
| ID: mdl-35845561
ABSTRACT
OBJECTIVE:
Arterial hypertension (AH) is the most common toxic effect of calcineurin inhibitor (CNI)-based immunosuppression in children after liver transplantation (LT). Activation of the renal sodium chloride cotransporter (NCC) by CNIs has been described as a major cause of CNI-induced AH. Thiazides, for example, hydrochlorothiazide (HCTZ), can selectively block the NCC and may ameliorate CNI-induced AH after pediatric LT.METHODS:
From 2005 thru 2015 we conducted a retrospective, single-center analysis of blood pressure in 2 pediatric cohorts (each n = 33) with or without HCTZ in their first year after LT. All patients received CNI-based immunosuppression. According to AAP guidelines, AH was defined as stage 1 and stage 2. Cohort 1 received an HCTZ-containing regimen to target the CNI-induced effect on the NCC, leading to AH. Cohort 2 received standard antihypertensive therapy without HCTZ.RESULTS:
In children who have undergone LT and been treated with CNI, AH overall was observed less frequently in cohort 1 vs cohort 2 (31% vs 44%; ns). Moreover, severe AH (stage 2) was significantly lower in cohort 1 vs 2 (1% vs 18%; p < 0.001). Multivariate analysis revealed HCTZ as the only significant factor with a protective effect on occurrence of severe stage 2 AH. While monitoring safety and tolerability, mild asymptomatic hypokalemia was the only adverse effect observed more frequently in cohort 1 vs 2 (27% vs 3%; p = 0.013).CONCLUSIONS:
Targeting NCC by HCTZ significantly improved control of severe CNI-induced AH and was well tolerated in children who underwent LT. This effect may reduce the risk of long-term end-organ damage and improve quality of life.
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Banco de datos:
MEDLINE
Tipo de estudio:
Guideline
Idioma:
En
Año:
2022
Tipo del documento:
Article