Risk Prediction In Long Term Kidney Transplant Recipients - Model Development Using Apelinergic Markers And Machine Learning Tools

Abstract

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 Statement

The authors have declared no competing interest.

Funding Statement

Yes

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

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.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

All relevant data are within the manuscript and its Supporting Information files.

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