Abstract
Renal transplant recipients (RTRs) are known to have a high cardio-vascular disease (CVD) burden only partly explained by traditional CVD risk factors. The aim of this paper was therefore to determine: i) the prognostic value of autoantibodies against apoA-1 (anti-apoA-1 IgG) for incidence of CVD mortality, all-cause mortality and graft failure in RTR. Four hundred and sixty two (462) prospectively included RTRs were followed for 7.0 years. Baseline anti-apoA-1 IgG were determined and associations with incidence of CVD mortality (n = 48), all-cause mortality (n = 92) and graft failure (n = 39) were tested. Kaplan–Meier analyses demonstrated significant associations between tertiles of anti-apoA-1 IgG and CVD mortality (log rank test: p = 0.048). Adjusted Cox regression analysis showed a 54% increase in risk for CVD mortality for each anti-apoA-1 IgG levels standard deviation increase (hazard ratio [HR]: 1.54, 95% Confidence Interval [95%CI]: 1.14–2.05, p = 0.005), and a 33% increase for all-cause mortality (HR: 1.33; 95%CI: 1.06–1.67, p = 0.01), independent of CVD risk factors, renal function and HDL function. The association with all-cause mortality disappeared after excluding cases of CVD specific mortality. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-apoA-1 positivity for CVD mortality were 18.0%, 89.3%, 17.0%, and 90.0%, respectively. HDL functionality was not associated with anti-apoA-1 IgG levels. This prospective study demonstrates that in RTR, anti-apoA-1 IgG are independent predictors of CVD mortality and are not associated with HDL functionality.
Highlights
Impaired kidney function is a major risk factor for cardiovascular diseases (CVD) through all stages of renal dysfunction, amounting to a substantial 40-fold increased risk of CVD mortality in end-stage renal disease (ESRD) patients [1,2]
The prevalence of high levels of anti-apoA-1 IgG was 11.5 % (53/462). [7,11,12,13,18] In order to better explore the architecture of anti-apoA-1 IgG in renal transplant recipients (RTRs), patients were divided into gender-stratified tertiles of anti-apoA-1 IgG, with median values of 0.15, 0.31, and 0.64 for the first, second and third tertile, respectively (Table 1)
Analyses between tertiles showed a significant difference for the history of myocardial infarction (MI), which was most common in patients with the highest levels of anti-apoA-1 IgG (p = 0.047), as well as for diabetic nephropathy (p = 0.04) as the primary renal disease
Summary
Impaired kidney function is a major risk factor for cardiovascular diseases (CVD) through all stages of renal dysfunction, amounting to a substantial 40-fold increased risk of CVD mortality in end-stage renal disease (ESRD) patients [1,2]. Autoantibodies against apoA-1 (anti-apoA-1 IgG) represent a recently identified biomarker with a high potential to predict increased CVD risk. Increased levels of these antibodies are associated with a pro-atherogenic lipid profile, a systemic pro-inflammatory state [6,7,8], as well as high-density lipoprotein (HDL) dysfunction [9,10], and were shown to be associated with increased CVD risk and poorer prognosis in high-risk patients, as well as in the general population [7,11,12,13,14]. As RTR are exposed to a uremic milieu prior to transplantation, they could constitute a risk-prone group to such a humoral autoimmunity phenomenon, despite receiving immunosuppressive treatment
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