Introduction Limited tools exist for predicting kidney function in long-term kidney transplant recipients (KTRs). Elabela and apelin are APJ receptor agonists that constitute the apelinergic axis, which is a recently discovered system regulating vascular and cardiac tissue, in opposition to renin-angiotensin-aldosterone. Methods Longitudinal, observational cohort of 101 KTRs who maintained graft function ≥24 months, with no acute rejection history or current active or chronic infection. Serum apelin, elabela, fibroblast growth factor 23 (FGF-23) and α-Klotho were tested using enzyme-linked immunoassay and compared with a control group of 32 healthy volunteers. Results Median (IQR) follow-up time was 84 (45, 87) months. Higher serum FGF-23 and elabela, but lower α Klotho concentrations were observed in KTRs. Most KTRs had stable trajectories of renal function. All candidate markers were significantly associated with mean two-year eGFR over follow-up, which itself was validated respective to ‘death with functioning graft’ censored dialysis requirement. Using a cross-validation approach, we demonstrated eGFR at initial visit as the most salient predictor of future renal function. Machine learning models incorporating both clinical and biochemical (candidate markers) assessments were estimated to explain 14% of variance in future eGFR when considering eGFR-independent predictions. Conclusions Utilization of machine learning tools that incorporate clinical information and biochemical assessments, including serum markers of the apelinergic axis, may help stratify risk and aid decision making in the care of long term KTRs.
Competing Interest StatementThe authors have declared no competing interest.
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The conduct of this study was in adherence with the Declaration of Helsinki principles, as well as International Conference on Harmonization/Good Clinical Practice regulations. Study approval was obtained from the Bioethics Committee of the Jagiellonian University and all patients provided written informed consent prior to study inclusion.
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