Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging
Chronic kidney disease (CKD) describes the loss of kidney function and affects 8-16% of the adults worldwide. It causes many age-related disabilities and even death. While CKD often leads to renal replacement, 80-90% of cases are asymptomatic. New biomarkers associated with reduced kidney function could help to diagnose CKD earlier, and provide insights into disease pathogenesis.
In a recent study, Yuko Yamaguchi from the Johns Hopkins University School of Medicine and colleagues looked for correlations between plasma metabolites and estimated glomerular filtration rate (eGFR) as well as with diagnosis of CKD. They used data from participants in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is a large, well-defined dataset, based on highly standardized procedures for data collection and laboratory analysis.
Firstly, the research team found that smokers have a higher risk of developing CKD. Next, the study revealed a high diversity of metabolites associated with CKD and eGFR. These findings suggest various metabolic pathways are involved in the disease pathophysiology, such as the urea cycle, the arginine-nitric oxide pathway, the polyamine pathway, and short chain acylcarnitine metabolism. Twenty-two metabolites were related to higher odd ratios of CKD. Higher levels of symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) levels in individuals with CKD may inhibit the arginine-nitric oxide pathway, leading to reduced levels of the urea cycle metabolite citrulline.
Fifty-one metabolites and the putrescine/ornithine ratio were negatively correlated with eGFR. The reduction of the ornithine/citrulline and proline/citrulline levels in individuals with CKD and lower eGFR suggests impaired arginase activity and polyamine synthesis. Similarly, levels of glycine compared to serin were elevated. A lower eGFR is suggested to cause alterations of short-chain acylcarnitine metabolism in patients with CKD. Finally, the levels of some metabolites, such as hippuric acid or 1-methylhistidine, suggest differences in dietary intake and gut microbiome between participants with CKD and participants without CKD.
Using robust statistical methods, and accounting for possible confounders, the study provides insights into the pathogenesis of CKD. These findings may be the basis for further analysis to identify possible biomarkers for CKD development and progression.
Applying metabolomics in large cohort studies has become the standard for biomarker discovery – for further examples, please observe our epidemiology literature section.
Yamaguchi Y, Zampino M, Moaddel R, Chen TK, Tian Q, Ferrucci L et al.: Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging. (2021) Metabolomics | https://doi.org/10.1007/s11306-020-01762-3