Novel biomarkers of renal transplant failure/dysfunction via spectroscopic phenotyping

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Title: Novel biomarkers of renal transplant failure/dysfunction via spectroscopic phenotyping
Authors: Payne, Thomas
Item Type: Thesis or dissertation
Abstract: Successful renal transplantation not only improves patients’ quality and duration of life, but also confers a substantial economic healthcare cost saving. With the growing burden of end-stage renal disease and the requirement for renal replacement therapy, strategies to augment transplant success and subsequent graft survival become more vital than ever. Herein, an objective means of characterising renal function across the transplant journey, and appropriately stratifying in accordance to individual contingencies/factors (including the early detection of renal dysfunction), based on metabolism is explored. Patient pairs, recipients and donors, were metabolically phenotyped prior to (24 h) and post (days 1–5) transplantation using a multi-platform analytical approach (i.e., Nuclear Magnetic Resonance Spectroscopy (NMR) and Mass Spectrometry (MS)) of urine and plasma (n = 50). Using advanced statistics, the resulting metabolic profiles were subsequently modelled, and related to multiple clinical phenotypes (and outcomes), to increase the understanding of molecular changes/signatures across transplantation, capturing valuable information pertinent to transplant type, cause, co-morbidity, modality, immunology and complication (p-value < 0.05) – over donors as well as recipients. An attempt to then develop predictive algorithms for the early detection of renal dysfunction was preliminary defined within the confines of the study design, where integrated NMR and MS metabolic data improved patient stratification for complications over clinical measures (receiver operator characteristic area under curve over 0.900) and potentially replace current measures. While prospective/multicentre studies are imperative for subsequent real-world adoption (qualification/validation), the work conducted herein encompassed much of the first stage of marker development – discovery – where metabolic phenotyping renal transplantation has provided a deeper characterisation of patient journeys with new insights into multiple contingencies/factors (including complication). Such findings infer the value of metabolic phenotyping to augment and potentially replace current measures and methods to better inform decision making in the clinic on the individual/precision level.
Content Version: Open Access
Issue Date: Oct-2017
Date Awarded: Jul-2018
URI: http://hdl.handle.net/10044/1/61777
Supervisor: Nicholson, Jeremy
Hakim, Nadey
Sponsor/Funder: Imperial College London
Department: Department of Surgery & Cancer
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses



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