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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI070119-08
Application #
8516962
Study Section
Special Emphasis Panel (ZAI1-MFH-I)
Project Start
2013-08-01
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
8
Fiscal Year
2013
Total Cost
$231,034
Indirect Cost
$34,847
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Oetting, W S; Jacobson, P A; Israni, A K (2016) Validation Is Critical for Genome-Wide Association Study-Based Associations. Am J Transplant :
Dorr, Casey R; Freedman, Barry I; Hicks, Pamela J et al. (2016) Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes. PLoS One 11:e0152775
Freedman, Barry I; Pastan, Stephen O; Israni, Ajay K et al. (2016) APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors. Transplantation 100:194-202
Oetting, W S; Schladt, D P; Guan, W et al. (2016) Genomewide Association Study of Tacrolimus Concentrations in African American Kidney Transplant Recipients Identifies Multiple CYP3A5 Alleles. Am J Transplant 16:574-82
Sanghavi, K; Brundage, R C; Miller, M B et al. (2015) Genotype-guided tacrolimus dosing in African-American kidney transplant recipients. Pharmacogenomics J :
Ong, Song; Mannon, Roslyn B (2015) Genomic and proteomic fingerprints of acute rejection in peripheral blood and urine. Transplant Rev (Orlando) 29:60-7
Ma, Jun; Divers, Jasmin; Palmer, Nicholette D et al. (2015) Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation. Kidney Int 88:584-92
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
Freedman, B I; Julian, B A; Pastan, S O et al. (2015) Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure. Am J Transplant 15:1615-22

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