Levels of Angiopoietin-Like-2 Are Positively Associated With Aortic Stiffness and Mortality After Kidney Transplantation.
BACKGROUND
Angiopoietin-like-2 (ANGPTL2) is a secreted proinflammatory glycoprotein that promotes endothelial dysfunction, atherosclerosis, and cardiovascular disease (CVD). Circulating ANGPTL2 is increased in chronic kidney disease (CKD), where the risk of CVD is amplified. The objectives of the present study were to (i) examine whether kidney transplantation (KTx) reduces ANGPTL2 levels, (ii) identify the determinants of ANGPTL2 after KTx, (iii) study the association of ANGPTL2 with aortic stiffness, and (iv) assess the impact of ANGPTL2 on mortality after KTx.


METHODS
In 75 patients, serum ANGPTL2 levels were measured at baseline and 3 months after KTx. Aortic stiffness was determined by carotid-femoral pulse wave velocity, glomerular filtration rate was estimated by CKD-EPI formula, and serum cytokines and endothlin-1 levels were determined 3 months after KTx. Survival analysis was performed using Kaplan-Meier and Cox regression after a median follow-up of 90 months.


RESULTS
After 3 months of KTx, ANGPTL2 levels decreased from 71 ng/ml (53-95) to 11 ng/ml (9-15) (P < 0.001). In multivariate analysis, age, lower renal function, and endothelin-1 were independently associated with higher post-KTx ANGPTL2 levels. ANGPTL2 was positively associated with aortic stiffness after KTx, even when adjusted for mean blood pressure (standardized β = 0.314; P = 0.008). During follow-up, 13 deaths occurred. The group of patients with higher post-KTx ANGPTL2 levels had a hazard ratio for mortality of 3.9 (95% confidence interval: 1.07-14.4; P = 0.039).


CONCLUSIONS
KTx significantly reduced serum ANGPTL2 levels. The positive association between post-KTx ANGPTL2, aortic stiffness and mortality, suggests that ANGPTL2 may play a biological role in CKD-related CVD.
CHU de Québec Research Center, L'Hôtel-Dieu de Québec hospital, Division of Nephrology, Department of medicine, Faculty of medicine, Université Laval, Québec City, Québec, Canada.
Marie-Pier
MP
Desjardins
Université de Montréal, Montreal Heart Institute, Department of Surgery, Montréal, Québec, Canada.
Nathalie
N
Thorin-Trescases
CHU de Québec Research Center, L'Hôtel-Dieu de Québec hospital, Division of Nephrology, Department of medicine, Faculty of medicine, Université Laval, Québec City, Québec, Canada.
Aboubacar
A
Sidibé
CHU de Québec Research Center, L'Hôtel-Dieu de Québec hospital, Division of Nephrology, Department of medicine, Faculty of medicine, Université Laval, Québec City, Québec, Canada.
Catherine
C
Fortier
CHU de Québec Research Center, L'Hôtel-Dieu de Québec hospital, Division of Nephrology, Department of medicine, Faculty of medicine, Université Laval, Québec City, Québec, Canada.
Sacha A
SA
De Serres
CHU de Québec Research Center, L'Hôtel-Dieu de Québec hospital, Division of Nephrology, Department of medicine, Faculty of medicine, Université Laval, Québec City, Québec, Canada.
Richard
R
Larivière
Université de Montréal, Montreal Heart Institute, Department of Surgery, Montréal, Québec, Canada.
Eric
E
Thorin
CHU de Québec Research Center, L'Hôtel-Dieu de Québec hospital, Division of Nephrology, Department of medicine, Faculty of medicine, Université Laval, Québec City, Québec, Canada.
Mohsen
M
Agharazii
D000328:Adult; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000601:surgery*; D016030:Kidney Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D063177:Pulse Wave Analysis; D015996:Survival Rate; D059289:Vascular Stiffness
C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D019332:Endothelin-1
angiopoietin-like-2; aortic stiffness; blood pressure; chronic kidney disease; hypertension; kidney transplantation; mortality.