Alexandra Bruel1,2, Justine Bacchetta1,3, Tiphanie Ginhoux4, Christelle Rodier-Bonifas5, Anne-Laure Sellier-Leclerc1, Bérengère Fromy6, Pierre Cochat1,3,6, Dominique Sigaudo-Roussel6, Laurence Dubourg7,8,9,10. 1. Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hospices Civils de Lyon, Lyon, France. 2. Service de Pédiatrie, Hôpital Mère et Enfants, Centre hospitalo-universitaire de Nantes, Nantes, France. 3. Université Claude Bernard Lyon 1, Lyon, France. 4. EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Lyon, France. 5. Service d'ophtalmologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 6. Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRS, University Claude Bernard Lyon 1, Villeurbanne, France. 7. Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hospices Civils de Lyon, Lyon, France. laurence.dubourg@chu-lyon.fr. 8. Université Claude Bernard Lyon 1, Lyon, France. laurence.dubourg@chu-lyon.fr. 9. Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRS, University Claude Bernard Lyon 1, Villeurbanne, France. laurence.dubourg@chu-lyon.fr. 10. Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Lyon, France. laurence.dubourg@chu-lyon.fr.
Abstract
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an orphan inborn error of oxalate metabolism leading to hyperoxaluria, progressive renal failure, oxalate deposition, and increased cardiovascular complications. As endothelial dysfunction and arterial stiffness are early markers of cardiovascular risk, we investigated early endothelial and vascular dysfunction in young PH1 patients either under conservative treatment (PH1-Cons) or after combined kidney liver transplantation (PH1-T) in comparison to healthy controls (Cont-H) and patients with a past of renal transplantation (Cont-T). METHODS: Skin microvascular function was non-invasively assessed by laser Doppler flowmetry before and after stimulation by current, thermal, or pharmacological (nitroprussiate (SNP) or acetylcholine (Ach)) stimuli in young PH1 patients and controls. RESULTS: Seven PH1-Cons (6 F, median age 18.2) and 6 PH1-T (2 F, median age 13.3) were compared to 96 Cont-H (51 F, median age 14.2) and 6 Cont-T (4 F, median age 14.5). The endothelium-independent vasodilatation (SNP) was severely decreased in PH1-T compared to Cont-H. Ach, current-induced vasodilatation (CIV), and thermal response was increased in PH1-Cons and Cont-T compared to controls. CONCLUSIONS: PH1-T patients displayed severely decreased smooth muscle capacity to vasodilate. An exacerbated endothelial-dependent vasodilation suggests a role for silent inflammation in the early dysfunction of microcirculation observed in PH1-Cons and Cont-T.
BACKGROUND:Primary hyperoxaluria type 1 (PH1) is an orphan inborn error of oxalate metabolism leading to hyperoxaluria, progressive renal failure, oxalate deposition, and increased cardiovascular complications. As endothelial dysfunction and arterial stiffness are early markers of cardiovascular risk, we investigated early endothelial and vascular dysfunction in young PH1patients either under conservative treatment (PH1-Cons) or after combined kidney liver transplantation (PH1-T) in comparison to healthy controls (Cont-H) and patients with a past of renal transplantation (Cont-T). METHODS: Skin microvascular function was non-invasively assessed by laser Doppler flowmetry before and after stimulation by current, thermal, or pharmacological (nitroprussiate (SNP) or acetylcholine (Ach)) stimuli in young PH1patients and controls. RESULTS: Seven PH1-Cons (6 F, median age 18.2) and 6 PH1-T (2 F, median age 13.3) were compared to 96 Cont-H (51 F, median age 14.2) and 6 Cont-T (4 F, median age 14.5). The endothelium-independent vasodilatation (SNP) was severely decreased in PH1-T compared to Cont-H. Ach, current-induced vasodilatation (CIV), and thermal response was increased in PH1-Cons and Cont-T compared to controls. CONCLUSIONS:PH1-Tpatients displayed severely decreased smooth muscle capacity to vasodilate. An exacerbated endothelial-dependent vasodilation suggests a role for silent inflammation in the early dysfunction of microcirculation observed in PH1-Cons and Cont-T.
Entities:
Keywords:
Cardiovascular risk; Endothelium; Hyperoxaluria type I; Microcirculation; Renal transplantation
Authors: Audrey Koïtka; Marie Sophie Legrand-Fernandez; Pierre Abraham; Lionel Fizanne; Bérengère Fromy; Dominique Sigaudo-Roussel; Jean Louis Saumet Journal: Microvasc Res Date: 2004-03 Impact factor: 3.514
Authors: Bernard I Levy; Ernesto L Schiffrin; Jean-Jacques Mourad; Denis Agostini; Eric Vicaut; Michel E Safar; Harry A J Struijker-Boudier Journal: Circulation Date: 2008-08-26 Impact factor: 29.690