Carbamylation in Chronic Kidney Disease: Comparative Biomarker Analysis and Implications for Cardiovascular Disease

Abstract

As the global incidence of chronic kidney disease (CKD) escalates, there is a pressing need to better understand its pathophysiology and associated morbidity. A focal point of such research is carbamylation, a post-translational protein modification driven primarily by elevated urea levels, notably prevalent among patients with CKD and end-stage kidney disease (ESKD). Investigating carbamylation holds promise for shedding light on its implications in the setting of declining kidney function, with the goal of identifying novel therapeutic avenues. In our first paper we focused on current biomarkers to assess carbamylation burden, we investigated the prognostic utility of carbamylated albumin (C-Alb) and homocitrulline (HCit) in predicting adverse clinical outcomes in CKD patients, drawing on data from 1632 individuals with stages 2-4 CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. The aim is to show that HCit is interchangeable with C-Alb as a prognostic marker. This interchangeability would be very useful to researchers in the field since it allows them to utilize HCit (as opposed to C-Alb) which is widely available in many metabolomic platforms. Our second paper focuses on the phenotypic correlates of carbamylation. We applied a Phenome Wide Association Study to uncover the phenotypic correlates of carbamylation, as we sought to investigate the systemic nature of carbamylation's effects beyond kidney function alone.