These continuation studies focus on large pancreas transplant alone (PTA), kidney transplant alone (KTA), and P after K (PAK) transplant populations of type 1 diabetic (D) patients (pts)in order to better understand diabetic nephropathy (DN), the leading cause of renal failure and calcineurin inhibitor toxicity (CNIT). Objectives are: (a) to determine whether PTA can more readily arrest or reverse the early vs. the more established lesions of DN;(b) to continue studies of renal structural-functional relationships in DN, with emphasis on the multifaceted pathologic DN lesions, including glomerular (G),vascular, interstitial (Int) lesions and glomerular-tubular junction abnormalities (GTJA) including atubular glomeruli (AG) and the reversibility of these lesions by PTA;(c) to continue studies of DN natural history and the role of renal biopsy in predicting outcome;(d) to elucidate G podocyte and endothelial cell abnormalities in DN and their reversibility by PTA;(e) to study the recurrence of DN in the KTA;(f) to study the molecular/genetic basis of DN and develop cellular markers of DN risk;(g) to determine the long-term structural and functional consequences of calcineurin inhibitors (CNI)on the native kidneys of PTA recipients;and (h) to determine the shorter-term (5 yr) consequences on the native kidneys of PTA recipients in order to more fully describe the pathology, compare cyclosporine to Prograf injury, and elucidate reversibility of these lesions with CNI dose reduction or discontinuation. Together, these studies will help to elucidate the pathogenesis and natural history of DN, unravel some of the molecular and genetic aspects of this disease, describe the dynamics of DN reversal in PTA and PAK pts,and recurrence in KTA pts and expand our knowledge of the nephrotoxic effects of CNIs.

Public Health Relevance

Diabetes is the single most important cause of kidney failure, responsible for more than 45% of all new cases in the USA. Certain drugs [calcineurin inhibitors (CNI)] used for prevention of rejection of transplanted organs cause kidney failure in as many as 20% of recipients. These studies will help to understand how diabetes and these drugs destroys the kidney and define the possibilities for healing of these injuries.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-R)
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University of Minnesota Twin Cities
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Verghese, Priya; Gillingham, Kristen; Matas, Arthur et al. (2016) Post-transplant blood transfusions and pediatric renal allograft outcomes. Pediatr Transplant 20:939-945
Ibrahim, Hassan N; Foley, Robert N; Reule, Scott A et al. (2016) Renal Function Profile in White Kidney Donors: The First 4 Decades. J Am Soc Nephrol 27:2885-93
Reilly-Spong, Maryanne; Reibel, Diane; Pearson, Terry et al. (2015) Telephone-adapted mindfulness-based stress reduction (tMBSR) for patients awaiting kidney transplantation: Trial design, rationale and feasibility. Contemp Clin Trials 42:169-84
International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) (2015) Design and Implementation of the International Genetics and Translational Research in Transplantation Network. Transplantation 99:2401-12
Wiebe, C; Nevins, T E; Robiner, W N et al. (2015) The Synergistic Effect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection and Graft Survival. Am J Transplant 15:2197-202
Harindhanavudhi, Tasma; Parks, Alicia; Mauer, Michael et al. (2015) Podocyte structural parameters do not predict progression to diabetic nephropathy in normoalbuminuric type 1 diabetic patients. Am J Nephrol 41:277-83
Mauer, Michael; Caramori, Maria Luiza; Fioretto, Paola et al. (2015) Glomerular structural-functional relationship models of diabetic nephropathy are robust in type 1 diabetic patients. Nephrol Dial Transplant 30:918-23
Robiner, William N; Flaherty, Nancy; Fossum, Thyra A et al. (2015) Desirability and feasibility of wireless electronic monitoring of medications in clinical trials. Transl Behav Med 5:285-93
Verghese, Priya S; Schmeling, David O; Knight, Jennifer A et al. (2015) The impact of donor viral replication at transplant on recipient infections posttransplant: a prospective study. Transplantation 99:602-8
Balfour Jr, Henry H (2014) Editorial commentary: Genetics and infectious mononucleosis. Clin Infect Dis 58:1690-1

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