Emerging Cardiovascular Risk Factors in Chronic Kidney Disease in the "Omics" Era: Gut and Beyond

Chronic kidney disease (CKD) is a significant public health problem worldwide because of its increasing prevalence and strong association with poor outcomes. In particular, patients with CKD have a disproportionately high risk of premature cardiovascular morbidity and mortality, which increases exponentially as CKD progresses to end-stage kidney disease. Whereas traditional cardiovascular risk factors are highly prevalent in patients with CKD, several nontraditional risk factors, such as inflammation, also come into play in cardiovascular diseases, especially in advanced CKD stages. Furthermore, recent advances in high-throughput "omics" technologies and sophisticated bioinformatics and modeling approaches have identified an increasing number of novel cardiovascular risk factors in CKD across various omics levels, including the microbiomics, proteomics, metabolomics, transcriptomics, epigenomics, and genomics. These molecular markers identified from high-dimensional omics data have not only advanced our understanding of cardiovascular disease mechanisms in CKD but also facilitated the development of target-driven therapeutic strategies to reduce excess cardiovascular morbidity and mortality in this population. However, significant challenges to their research and clinical applications remain, including the high cost of multiomics profiling and the complexity of assessing comparative cardiovascular risk between multidimensional omics data across different stages of CKD. In this article, based on a comprehensive literature search on PubMed and Google Scholar, we review emerging cardiovascular risk factors in the era of integrated multidimensional omics approaches, with an emphasis on recent findings from microbiomics, and discuss their prognostic implications, current challenges, and future directions in the context of translational epidemiology toward improving cardiovascular outcomes in patients with CKD.