title: Clinical and plasma proteomic markers correlating with chronic kidney disease after liver transplantation.
abstract: Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline glomerular filteration rate (GFR) >60 at the time of LT and are now >3 years post-LT. Risk factors for post-LT CKD were compared between three different groups defined by current GFR: >90 (n = 40), 60-90 (n = 146) and <60 (n = 156) mL/min. Age, cyclosporine use and pre-LT GFR were independently associated with new onset CKD. A subset (n = 64) without viral/immune disease or graft dysfunction underwent multianalyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n = 22) and validation (n = 42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multicenter study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function.
authors.affiliation: Comprehensive Transplant Center Division of Hepatology, Northwestern University, Chicago, IL, USA. j-levitsky@northwestern.edu
authors.forename: J
authors.initials: J
authors.lastname: Levitsky
authors.forename: D R
authors.initials: DR
authors.lastname: Salomon
authors.forename: M
authors.initials: M
authors.lastname: Abecassis
authors.forename: P
authors.initials: P
authors.lastname: Langfelder
authors.forename: S
authors.initials: S
authors.lastname: Horvath
authors.forename: J
authors.initials: J
authors.lastname: Friedewald
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: S M
authors.initials: SM
authors.lastname: Kurian
authors.forename: T
authors.initials: T
authors.lastname: Mondala
authors.forename: S
authors.initials: S
authors.lastname: Gil
authors.forename: R
authors.initials: R
authors.lastname: McDade
authors.forename: K
authors.initials: K
authors.lastname: Ballard
authors.forename: L
authors.initials: L
authors.lastname: Gallon
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D040901:Proteomics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins