We propose to investigate the pharmacogenomics ofthe calcineurin inhibitors (CNI) and mycophenolate in kidney transplantation. Despite the tremendous therapeutic advances that these drugs have provided, their use is still limited by toxicities and therapy failures. Unfortunately, we are unable to discern which patients will develop toxicity or fail therapy. For these patients the consequences can be severe including return to dialysis, retransplantation and death. Monitoring of blood levels has improved our ability to improve and tailor therapy once immune suppression is initiated;however, initial doses are largely empiric and use the crude

Public Health Relevance

Immunosuppressive drugs are associated with substantial toxicities and some patients fail therapy. Genetic factors may be associated with these events. Pretransplant testing for these factors will allow for the tailoring of regimens to the individual with the greatest chance of success.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-MFH-I)
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University of Minnesota Twin Cities
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Oetting, William S; Guan, Weihua; Schladt, David P et al. (2014) Telomere length of recipients and living kidney donors and chronic graft dysfunction in kidney transplants. Transplantation 97:325-9
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Passey, Chaitali; Birnbaum, Angela K; Brundage, Richard C et al. (2011) Dosing equation for tacrolimus using genetic variants and clinical factors. Br J Clin Pharmacol 72:948-57
Mannon, Roslyn B (2010) Immune monitoring and biomarkers to predict chronic allograft dysfunction. Kidney Int Suppl :S59-65

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