Plasma acylcarnitines and incident kidney outcomes in apparently healthy adults

Abstract Background Conventional diagnostic markers, such as eGFR or albuminuria, often detect established late stages of kidney disease missing early adaptive changes. Acylcarnitines (ACs), intermediates of mitochondrial fatty acid oxidation, have been suggested as markers of metabolic dysfunction and impaired energy metabolism, which are important processes in early kidney injury. However, their role as prognostic biomarkers for early kidney disease remains unclear. Aim To analyse ACs as an early prognostic biomarker for progression to kidney disease in an apparently healthy European population-based sample. Methods Data from 1 960 apparently healthy adults in a population-based cohort in Lausanne, Switzerland. Incident chronic kidney disease (CKD) was defined as progression to eGFR<60 mL/min/1.73 m² and eGFR trajectory as progression from eGFR >90 mL/min/1.73 m² to eGFR 60-90 mL/min/1.73 m² during the follow-up period. Results Over a median follow-up of 8.5 years, 53 participants (2.7%) developed CKD, and 365 participants (18.4%) developed eGFR trajectory. In multivariate analyses, long-chain ACs (Arachidonyl-) remained positively associated with incident CKD and their baseline standardized log-transformed concentrations AC levels were higher. Baseline levels of short-chain ACs (Butyryl- and Hydroxybutyryl-), long-chain ACs (Tetradecanedienoyl-, Hexadecenoyl-, Stearoyl- and Oleoyl-) were significantly higher in the participants who later developed eGFR trajectory. Conclusion ACs were independently associated with both incident CKD and eGFR trajectory in healthy adults free from diabetes, obesity or cardiovascular disease. However, the findings of the current study cannot establish the clinical utility of ACs profiling as a prognostic marker for prognostic CKD and require confirmation in studies with sufficient events.