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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Vezina, Heather E; Brundage, Richard C; Balfour Jr, Henry H (2014) Population pharmacokinetics of valganciclovir prophylaxis in paediatric and adult solid organ transplant recipients. Br J Clin Pharmacol 78:343-52
Balfour Jr, Henry H (2014) Editorial commentary: Genetics and infectious mononucleosis. Clin Infect Dis 58:1690-1
Nevins, Thomas E; Robiner, William N; Thomas, William (2014) Predictive patterns of early medication adherence in renal transplantation. Transplantation 98:878-84
Balfour Jr, Henry H (2014) Progress, prospects, and problems in Epstein-Barr virus vaccine development. Curr Opin Virol 6:1-5
Verghese, Priya S; Dunn, Ty B; Chinnakotla, Srinath et al. (2014) Calcineurin inhibitors in HLA-identical living related donor kidney transplantation. Nephrol Dial Transplant 29:209-18
Suszynski, Thomas M; Rizzari, Michael D; Gillingham, Kristen J et al. (2013) Antihypertensive pharmacotherapy and long-term outcomes in pediatric kidney transplantation. Clin Transplant 27:472-80
Najafian, Behzad; Mauer, Michael (2013) Predilection of segmental glomerulosclerosis lesions for the glomerulotubular junction area in type 1 diabetic patients: a novel mapping method. PLoS One 8:e69253
Mauer, Michael; Fioretto, Paola (2013) Pancreas transplantation and reversal of diabetic nephropathy lesions. Med Clin North Am 97:109-14
Ponchiardi, Cecilia; Mauer, Michael; Najafian, Behzad (2013) Temporal profile of diabetic nephropathy pathologic changes. Curr Diab Rep 13:592-9
Suszynski, T M; Gillingham, K J; Rizzari, M D et al. (2013) Prospective randomized trial of maintenance immunosuppression with rapid discontinuation of prednisone in adult kidney transplantation. Am J Transplant 13:961-70

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