Seibert, Stephan2019-06-102019-06-102017-06https://hdl.handle.net/11299/203519Tacrolimus (TAC) is used for immunosuppression after kidney transplantation. Non-optimal TAC therapy contributes to renal toxicity, graft damage, and rejection. This paper reviews publications associating TAC intra-patient pharmacokinetic variability with long- and short-term transplant outcomes. The literature was reviewed performing systematic searches of MEDLINE and EMBASE databases from 1990 to May 2016 using appropriate Medical Subject Headings (MeSH) and key words. Titles and abstracts of hits were scanned for relevance, resulting in nine articles included in this analysis. Included articles were evaluated for content and relevance, and summarized. All studies were relatively small (N <400) non-randomized retrospective chart reviews. Only two articles did not show significant association between variability of TAC trough concentrations and at least one outcome after kidney transplantation. Four studies analyzing acute rejection (AR) showed significant association, while two did not. All studies analyzing graft loss or composite outcomes including graft loss showed significant association. Other studies showed association with donor-specific-antibody (DSA) development, but no association with renal function decline or overall patient survival. This review indicates an overall trend towards worse transplant outcomes in patients with higher TAC pharmacokinetic variability, however the size and design of the studies limit generalizability. Larger studies with more robust design are needed and should include genetic subgroup analysis and identification of sources of TAC variability to come to a definitive conclusion. Ideally, a dosing protocol incorporating wide varieties of genetic and clinical factors should be developed to optimize TAC dosing in transplant patients.enArticle