title: Time-series analysis in the medical domain: a study of Tacrolimus administration and influence on kidney graft function.
abstract: There exists a major concern regarding toxic effects of immunosuppressive medication on the kidney graft during post-transplant care, with observed variation in individual susceptibility to adverse drug effects amongst patients. To date, there has been no possibility to identify susceptible patients prospectively. This study analyzes medical data which includes time series of measures of renal function and trough levels of immunosuppressive drug Tacrolimus, with the main aim of identifying patients susceptible to drug toxicity. We evaluate a plethora of time-series distance measures, determining their appropriateness to the domain based on two criteria: (1) preserving the expected correlations between distances, and (2) ability to detect the expected patterns of interaction between immunosuppressive drug levels and renal function. Besides identifying the most suitable time-series distance measures, we observed that the majority of patients do not exhibit an association between impaired graft function and higher Tacrolimus dosing. On the other hand, the minority of patients determined most sensitive to varying Tacrolimus levels showed a strong tendency to prefer low Tacrolimus dosing.
authors.affiliation: University of Novi Sad, Faculty of Science, Department of Mathematics and Informatics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia. Electronic address: kurba@dmi.uns.ac.rs.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kurbalija
authors.affiliation: University of Novi Sad, Faculty of Science, Department of Mathematics and Informatics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia. Electronic address: radacha@dmi.uns.ac.rs.
authors.forename: Miloš
authors.initials: M
authors.lastname: Radovanović
authors.affiliation: University of Novi Sad, Faculty of Science, Department of Mathematics and Informatics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia. Electronic address: mira@dmi.uns.ac.rs.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Ivanović
authors.affiliation: Charité - Universitätsmedizin Berlin, Department of Nephrology, Campus Charité Mitte, Germany. Electronic address: danilo.schmidt@charite.de.
authors.forename: Danilo
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Humboldt University of Berlin, Department of Computer Science, Germany. Electronic address: gabriela.lindemann@uv.hu-berlin.de.
authors.forename: Gabriela Lindemann
authors.initials: GL
authors.lastname: von Trzebiatowski
authors.affiliation: Humboldt University of Berlin, Department of Computer Science, Germany. Electronic address: hdb@informatik.hu-berlin.de.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Burkhard
authors.affiliation: Charité - Universitätsmedizin Berlin, Department of Nephrology, Campus Virchow-Hospital, Germany. Electronic address: carl.hinrichs@charite.de.
authors.forename: Carl
authors.initials: C
authors.lastname: Hinrichs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D051437:Renal Insufficiency / Q000628:therapy; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus
keywords: Creatinine; Distance measures; Glomerular filtration rate; Kidney transplantation; Tacrolimus; Time series