Late graft loss continues to be a major problem after kidney transplantation (KT), mainly as consequence of death with a functioning graft and intrinsic allograft failure (or chronic allograft dysfunction (CAD)). CAD remains a major cause of allograft attrition over time, resulting in reinstitution of end-stage renal disease care. CAD is considered by many to be a variant of chronic kidney disease (CKD), with both immune and non-immune mechanisms, contributing to the development of interstitial fibrosis, tubular atrophy (IFTA) and progressive loss of graft function.CAD remains a major cause of allograft attrition over time, resulting in reinstitution of end-stage renal disease care. Hereby, the proposed strategies aim to decrease health care costs, reduce patient morbidity / mortality and improve quality of life by early prediction and subsequent prevention of graft loss due to CAD.The specific aims (SA) include: SA1: Determine post-KT epigenetic modifications sequentially from a longitudinal cohort of human renal allograft biopsies. SA2: Develop predictive models to stratify the risk of developing fibrosis and function loss by integrating the most predictive epigenetic, transcriptome, and clinical markers. SA3: Evaluate circulating small non-coding RNA (sncRNA) profiles to identify biomarkers and correlate with gene expression changes in the renal allograft with fibrosis and CAD. Evaluation of epigenetic changes in kidney grafts may provide new data about affected pathways and regulators leading to graft injury, fibrosis, and loss of function. The proposed studies will provide information about the effect of epigenetic modifications on molecular pathways and upstream regulators leading to CAD. Resulting non-invasive biomarkers will better predict and stratify graft injury and fibrosis progression, potentially improving long-term renal graft outcomes.
|Effective start/end date||7/1/20 → 6/30/24|
- University of Maryland, Baltimore (19283 Amendment 3 // 5R01DK122682-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (19283 Amendment 3 // 5R01DK122682-05)
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