Multi-Omics for Chronic Kidney Disease

Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality, with a prevalence estimated at 13% in the U.S. that continues to increase annually. The etiology of CKD is complex, with both genetic – including monogenetic and polygenic – and environmental contributions playing major roles. CKD is determined by a combination of environmental and inherited factors. Multi-omic approaches including genetics, epigenetics, transcriptomics, proteomics, and metabolomics are high-throughput technologies being leveraged for precision medicine that hold great potential to improve diagnosis and clinical care for complex diseases such as CKD. As part of the Multi-omics Health and Disease Consortium, this proposal will establish a Disease Study Site (DSS) focused on CKD. Our rationale for selecting CKD is three-fold: 1) CKD has high cost and public health impact in the U.S.; 2) CKD represents an important modifier of multi-omic profiles in other common conditions; and 3) there is an urgent, unmet need to provide molecular disease subclassification in CKD – and in particular non-diabetic CKD – as the current diagnosis relies solely on functional rather than molecular criteria. Our hypothesis is that longitudinal blood and urine multi-omics can provide non-invasive means to better subclassify non-diabetic CKD, and thus provide a new precision medicine-based approach for this condition. We propose a prospective study of 200 CKD patients and 100 non-CKD controls. We will address the following questions: What are the molecular correlates of longitudinal decline in renal function? Are there specific molecular subtypes of non-diabetic CKD identifiable by longitudinal multi-omics? What are the roles of environmental exposures, social and economic stressors, and genetics in determining molecular CKD subtypes? Our team involves national leaders in Precision Medicine and has a track record of successful execution of genetic, epidemiologic, and interventional studies. We will coordinate efficient local recruitment of our prospective cohort using innovative outreach methods. Our long-term goal is to challenge the existing clinical paradigms in CKD and pilot the use of integrative multi-omics to advance precision nephrology.