Endothelial deficiency in Pkd1 impairs the development of arterio-venous fistula - 25/09/20
, D. Nezam 1, 2, M. Hamzaoui 1, 2, A. Dumenil 1, S. Renet 1, V. Richard 1, J. Bellien 1, 3, D. Guerrot 1, 2
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Résumé |
Introduction |
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is mainly due to mutations in PKD1 which encode for polycystin 1 (PC1). PC1 is a transmembrane protein, located on the primary cilium of endothelial cells and epithelial renal cells, and acts as a blood or urinary flow sensor. In ADPKD, this mechanotransductory mechanism is altered, and leads to cyst formation and vascular abnormalities. In ADPKD, after decades, patients may reach End Stage Renal Disease (ESRD) requiring Hemodialysis. An arterio-venous fistula (AVF) created by an anastomosis between an artery and a vein is the preferred vascular access to perform hemodialysis. However, in ADPKD there are more immediate AVF failures, the mechanisms of which remain unknown.
Method |
We developed a model of aorto-cava AVF in C57bl/6J mice. Two groups were compared: mice with endothelial specific knock-out of Pkd1 (iCdh5-cre; Pkd1del/del) induced at birth vs. control mice (Pkd1lox/lox). We performed Doppler ultrasonography at D0, D1 and D14 after surgery.
Results |
The overall survival did not differ between groups (82.3% in iCdh5-cre; Pkd1del/del vs. 81.3% in Pkd1lox/lox). An increase in venous flow demonstrated success of AVF in both iCdh5-cre; Pkd1del/del (D0: 10.3μL/s vs. D1: 32.4μL/s P=0.02) and Pkd1lox/lox mice (D0: 11.3μL/s vs. D1: 30.0μL/s P=0.07). In iCdh5-cre; Pkd1del/del mice the venous blood flow did not increase significantly between D0 and D14 (D0: 10.3 vs. D14: 29.6μL/s p: ns), as opposed to control mice (D0: 11.3 vs. 49.0μL/s P<0.01), demonstrating maturation failure in iCdh5-cre; Pkd1del/del mice.
Conclusion |
The results of this study demonstrate that endothelial Pkd1 is required for the development of AVF.
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Vol 12 - N° 2-4
P. 211 - octobre 2020 Retour au numéro
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