Plasma acylcarnitine profiling reveals heart failure-specific fatty acid oxidation signature in chronic kidney disease.

Acylcarnitines are key intermediates in fatty acid oxidation (FAO). Chronic kidney disease (CKD) and heart failure (HF) both alter FAO. However, it is unclear whether specific FAO changes are associated with CKD coupled with HF. Aim is to investigate alterations in various chain acylcarnitines in patients with CKD with and without HF and examine their independent associations. In a case-control study at the University of Michigan (2010-2022), 562 participants with HF and available plasma samples were selected and compared with 461 participants without HF, frequency matched by CKD stage. Plasma samples were retrieved for mass spectrometry-based acylcarnitine quantification. Mean age (± standard deviation) was 65 ± 14 years in HF and 54 ± 14 years in those without HF. We observed a significant increase in short-chain acylcarnitine (SCAC) and medium-chain acylcarnitine (MCAC) but a decrease in long-chain acylcarnitines (LCACs) due to the worsening stage of CKD in the absence of HF. In patients with HF, the slope of changes in SCAC and LCAC was mitigated, whereas the increase in MCAC due to worsening CKD stage was greater than that in the absence of HF. The mean SCAC, MCAC, and LCAC scores were significantly different at CKD stage 4 in HF versus those without HF (P ≤ 0.002). These findings suggest that CKD with HF is characterized by impaired β-oxidation of MCAC and LCAC and greater myocardial utilization of short-chain fatty acids. Inefficient β-oxidation coupled with the accumulation of MCAC and LCAC may in part explain the poorer outcomes in the HF-CKD complex.