Background
Currently 15% of patients on the Irish Kidney Transplant Waiting List are highly sensitised and at higher risk of rejecting a transplanted kidney. Recent data have shown that acute cellular rejection (ACR) in the first year post transplant may lead to histological changes in up to 45% of patients that are predictive of transplant loss. Sentinel skin flaps (SSF) have been demonstrated to provide a dynamic canvas that can diagnose and monitor ACR in a transplanted visceral organ in real time. Development of a skin rash on the SSF in ACR, preceded or was concordant with organ rejection. A skin biopsy allowed early diagnosis of ACR and an opportunity to tailor immunosuppression, limiting injury to the kidney.
Aims & Hypothesis
The primary objective of this study is to explore the feasibility of performing a more comprehensive study of the utility and mechanism of action of a SSF combined with a kidney or kidney+/-pancreas transplant for diagnosing and monitoring ACR in highly sensitised transplant patients. The relative susceptibility of skin to rejection (development of a skin rash), allows early evidence of an alloresponse which can be easily identified by patients and an opportunity to initiate prompt immunosuppressive therapy. This pilot study will provide preliminary data to determine the feasibility of performing a clinical trial to test the effectiveness of SSF as a biomarker for diagnosing and monitoring early ACR and personalising immunosuppression prescribing in highly sensitised kidney transplant, along with providing preliminary data on mechanisms leading to immunomodulation (tolerance induction). The secondary objectives are to establish if discordant rejection occurs between the SSF and kidney; and biomarker analysis examining perturbations in cellular and molecular markers within the SSF, peripheral blood and skin microbiome.