P0691LIPOPROTEIN(A) AS A POTENTIAL RISK FACTOR FOR CARDIOVASCULAR (CV) AND THROMBOTIC EVENTS IN CHRONIC KIDNEY DISEASE (CKD) AND TRANSPLANTED PATIENTS
Authors: Simone Simona , Cianciotta Francesca , Sallustio Fabio , Pesce Francesco , Grandaliano Giuseppe , Gesualdo Loreto , Giovanni Pertosa 
Published: June 2020

Abstract

Background and Aims
Several studies suggested an independent association between elevated Lipoprotein (a) [Lp(a)] levels and the incidence of CV events in the normal population. Lp(a) levels start to rise with decreasing glomerular filtration rate. Whether high Lp(a) serum levels may contribute to the pathogenesis of atherosclerosis or thrombosis in CKD and, particularly, in transplanted (Tx) patients is largely unclear. Furthermore, it is still uncertain to which extent very high Lp(a) levels might influence CV events in this population. Aims: 1. To evaluate Lp(a) serum concentrations and lipid profile in CKD, dialysis and Tx patients. 2. To investigate the relationship between Lp(a) serum levels and atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, coronary revascularization, cerebrovascular accident, carotid endarterectomy, peripheral revascularization, gangrene, or limb amputation. 3. To assess whether Lp(a) may have a role in thrombotic events (failure of vascular access in HD or early renal allograft thrombosis after transplantation) in these patients.

Method
Serum Lp(a) levels and lipid profile were assessed in 295 patients (M 172, F 123; mean age 57.3, range 19-85 years): 23 with CKD stage I-III, 76 with CKD stage IV-V, 128 on dialysis (68 hemodialysis (HD), 60 peritoneal dialysis) and 68 were kidney Tx recipients (eGFR&gt;30 ml/min). In the latter group, Lp(a) values were assayed before and after transplantation. Lp(a) levels were determined using the Macra® Lp(a) ELISA kit (Trinity Biotech, USA). Values are expressed as median and interquartile range. Logistic regression analysis was used to determine whether Lp(a) is a risk factor for CV and thrombosis disease. The cut-off value was identified according to maximum Youden index by receiver operating characteristic (ROC) curve.

Results
Increased mean serum levels of LDL-C (93.85 mg/d; normal values=&lt;70 mg/dl) were observed in all groups of patients, while HDL-C and triglycerides serum levels were in the normal range. Serum Lp(a) levels (nv=14-31 mg/dl) were significantly (p&lt;0.001) increased in advanced CKD group (stage IV-V) (45.5, 1.5-216.5 mg/dl) and, mostly, in patients on dialysis treatment (63.2, 2.0-216.6 mg/dl, p=0.001) compared to mild-moderate CKD group (stage I-III) (32, 1.3-149 mg/dl). Lp(a) serum levels correlated significantly with age (r=0.11, p&lt;0.05) and, inversely, with eGFR only in advanced CKD group (r=-0.21 p&lt;0.05). A significant (-56%; p&lt;0.001) decrease of serum Lp(a) was observed after renal Tx, while staying in HD for another year resulted in an increase in serum Lp (a) levels of about 23.7% (p&lt;0.003). No significant relationship was found between Lp(a) values and gender, inflammation (as assessed by serum C-reactive protein levels), or diabetes. By logistic regression analysis, Lp(a) values were found to be a risk factors for ASCVD in the whole population (No events 246 pts: Lp(a) 47.8 mg/dl; Yes events 49 pts: Lp(a) 53.8 mg/dl; p=0.049) and for thrombotic events in HD group (vascular access thrombosis: 4 events) and Tx patients (early acute renal vein thrombosis after Tx: 4 events) (p=0.028). The ROC curve (AUC 0.7829, 95% CI 0.5751-0.9907) allowed us to define the cut-off value for serum Lp(a) (82.45 mg/dl) (sensitivity of 87%; specificity of 73%) as a thrombotic risk factor in HD and Tx patients.

Conclusion
The study confirms the relevance of Lp(a) as non-traditional CV risk factor in CKD and Tx patients predicting both, the development of ASCVD and thrombosis. Serum Lp(a) levels higher than 82.45 mg/dl are potential thrombotic risk factors for vascular access failure in HD patients or early acute renal allograft thrombosis in Tx patients, suggesting more aggressive strategies to lower Lp(a) serum levels in this patient setting.