Lipoprotein(a) and chronic kidney disease: reciprocal associations, potential causal pathways, and clinical implications

Chronic kidney disease (CKD) leads to multiple metabolic disorders which raise both the cardiovascular and non-cardiovascular mortality, especially in end-stage kidney disease (ESKD) patients. Among the dysmetabolic CKD-associated patterns, dyslipidemia shows a wide spectrum of clinical concurrent presentations, involving high serum levels of triglycerides, cholesterol, and lipoproteins such as Lp(a). International consensus statements and guidelines have highlighted the increased cardiovascular risk associated with higher serum Lp(a) levels > 105 nmol/L due to its pro-atherosclerotic and pro-thrombotic effects. Therefore, its assessment should be recommended at least once in a lifetime, due to the relative stability of Lp(a) serum levels over time. CKD is associated with increased Lp(a) concentrations, which rise as the estimated glomerular filtration rate (eGFR) and/or urinary albumin-to-creatinine ratio (UACR) worsen. Consequently, Lp(a) levels may be five-to-tenfold higher in patients with ESKD than in those with mild-to-moderate CKD. This alteration is mainly attributable to impaired renal clearance of Lp(a) and apolipoprotein(a) [Apo(a)] particles and, under specific conditions, to increased hepatic Lp(a) production, as observed in severe proteinuric diseases. Conversely, Lp(a) genetic determinants of elevated Lp(a) levels and increased serum Lp(a) concentrations have been investigated as potential causes of CKD onset, through Mendelian randomization (MR) and prospective studies, respectively. However, uncertainty and important gaps in the available evidence still remain. The aim of this review is to summarize and discuss the most recent and relevant clinical and experimental evidence on this topic through a defined research among the scientific literature.