title: Tacrolimus exposure in the real world: an analysis from the Mycophenolic acid Observational REnal transplant study.
abstract: Tacrolimus exposure and renal function data to 36 months post-transplant were analyzed from the prospective, observational Mycophenolic acid Observational REnal transplant (MORE) registry in which de novo kidney transplant patients were managed according to local practice. Tacrolimus trough (C0 ) concentration at month 12 was stratified as low (<6 ng/mL), moderate (6-8 ng/mL), or high (>8 ng/mL) in 724 patients. Estimated glomerular filtration rate (eGFR) was stratified as low (<60 mL/min/1.73 m(2) ) or high (≥60 mL/min/1.73 m(2) ). High tacrolimus C0 (>8 ng/mL) was observed in 47.7%, 34.1%, 26.8%, and 26.7% of patients at baseline and months 12, 24, and 36, respectively. Biopsy-proven acute rejection was similar to month 36 regardless of tacrolimus C0 category at month 12. Tacrolimus C0 >8 ng/mL vs. <6 ng/mL at month 12 was predictive of low eGFR at month 24 (p = 0.023) with a nonsignificant trend at month 36 (p = 0.085). Infections (p < 0.013) and BK virus infection (p < 0.001) were most frequent in the low tacrolimus C0 cohort. Neutropenia was most frequent in the high tacrolimus C0 category (p = 0.010). In conclusion, over a quarter of patients were exposed to high tacrolimus C0 to 36 months post-transplant. Tacrolimus exposure did not affect rejection risk, but tacrolimus C0 >8 ng/mL at month 12 was predictive of subsequent low eGFR compared to C0 <6 ng/mL.
authors.affiliation: Division of Nephrology, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Fuad S
authors.initials: FS
authors.lastname: Shihab
authors.forename: Ali
authors.initials: A
authors.lastname: Olyaei
authors.forename: Anne
authors.initials: A
authors.lastname: Wiland
authors.forename: Kevin
authors.initials: K
authors.lastname: McCague
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Norman
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000188:drug therapy / Q000209:etiology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Mycophenolic acid Observational REnal transplant; clinical; dose; evolution; exposure; kidney transplantation; reduction; tacrolimus