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Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing
Dagmara McGuinness1, Johannes Leierer2, Olivier Shapter1
1University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
Introduction:
Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.
Methodology:
The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts.
Results:
Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation.
Conclusion:
These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia.
Insights
A new scoring system using microRNAs (miRNAs) and donor factors can predict delayed graft function in kidney transplants. This molecular assay offers a rapid way to assess allograft function and potential interventions.
Area of Science:
- Nephrology
- Transplantation Immunology
- Molecular Biology
Background:
- Delayed graft function (DGF) is a common complication after kidney transplantation.
- DGF increases hospitalization and risk of other post-transplant complications.
- Current methods lack objective prediction systems for DGF.
Purpose of the Study:
- To investigate the role of microRNAs (miRNAs) in renal allograft performance.
- To develop a predictive model for delayed graft function in kidney transplantation.
Main Methods:
- Measured expression of specific microRNAs (miRNAs) in pre-transplant renal biopsies using qPCR.
- Correlated miRNA expression with clinical parameters and outcomes in two independent cohorts.
- Developed a renal performance scoring system (GRPSS) incorporating miRNA expression, donor age, and donation type.
Main Results:
- A novel pre-transplant renal performance scoring system (GRPSS) accurately predicts DGF.
- The GRPSS achieved high sensitivity (>90%) and specificity (>60%) in predicting DGF.
- The system utilizes three senescence-associated miRNAs, donor age, and organ donation type.
Conclusions:
- Pre-transplant miRNA levels correlate with cellular aging pathways and transplant outcomes.
- A simple, quantitative molecular assay can predict post-transplant allograft function.
- Senescence pathways are involved in ischemic injury, and accelerated bio-aging is a consequence of ischemia.
