Skin microvascular dysfunction as an early cardiovascular marker in primary hyperoxaluria type I

• Published in: Pediatric nephrology (Berlin, West) West), 2019-02, Vol.34 (2), p.319-327
• Main Authors: Bruel, Alexandra, Bacchetta, Justine, Ginhoux, Tiphanie, Rodier-Bonifas, Christelle, Sellier-Leclerc, Anne-Laure, Fromy, Bérengère, Cochat, Pierre, Sigaudo-Roussel, Dominique, Dubourg, Laurence
• Format: Article
• Language: English
• Subjects: Acetylcholine; Adolescent; Adult; Age; Cardiovascular diseases; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - etiology; Cardiovascular Diseases - physiopathology; Care and treatment; Case-Control Studies; Causes of; Child; Child, Preschool; Conservative Treatment; Diagnosis; Doppler effect; Endothelium; Endothelium, Vascular - physiopathology; Female; Genetic aspects; Humans; Hyperoxaluria; Hyperoxaluria, Primary - complications; Hyperoxaluria, Primary - physiopathology; Hyperoxaluria, Primary - therapy; Kidney Transplantation; Laser-Doppler Flowmetry; Life Sciences; Liver Transplantation; Male; Medicine; Medicine & Public Health; Microvasculature; Microvessels - diagnostic imaging; Microvessels - physiopathology; Muscle, Smooth, Vascular - physiopathology; Nephrology; Original Article; Oxalic acid; Patients; Pediatrics; Primary hyperoxaluria; Prospective Studies; Rare Diseases - complications; Rare Diseases - physiopathology; Rare Diseases - therapy; Renal failure; Skin; Skin - blood supply; Smooth muscle; Time Factors; Treatment Outcome; Urology; Vascular Stiffness - physiology; Vasodilation; Vasodilation - physiology; Young Adult
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-018-4081-5

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.