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
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
Claes, Kathleen J; Heye, Sam; Bammens, Bert et al. (2013) Aortic calcifications and arterial stiffness as predictors of cardiovascular events in incident renal transplant recipients. Transpl Int 26:973-81
Israni, Ajay K; Leduc, Robert; Jacobson, Pamala A et al. (2013) Inflammation in the setting of chronic allograft dysfunction post-kidney transplant: phenotype and genotype. Clin Transplant 27:348-58
Israni, Ajay K; Riad, Samy M; Leduc, Robert et al. (2013) Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics. Transpl Int 26:982-9
Jacobson, Pamala A; Schladt, David; Israni, Ajay et al. (2012) Genetic and clinical determinants of early, acute calcineurin inhibitor-related nephrotoxicity: results from a kidney transplant consortium. Transplantation 93:624-31
Jacobson, Pamala A; Schladt, David; Oetting, William S et al. (2011) Genetic determinants of mycophenolate-related anemia and leukopenia after transplantation. Transplantation 91:309-16
Jacobson, Pamala A; Oetting, William S; Brearley, Ann M et al. (2011) Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium. Transplantation 91:300-8
Oetting, William S; Schladt, David P; Leduc, Robert E et al. (2011) Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort. Transpl Int 24:1231-8
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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