title: Serum aminoacylase-1 is a novel biomarker with potential prognostic utility for long-term outcome in patients with delayed graft function following renal transplantation.
abstract: Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67-0.85) for ACY-1, 0.9 (0.84-0.95) for cystatin C, and 0.93 (0.88-0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor-brain-dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation.
authors.affiliation: 1] Clinical and Biomedical Proteomics Group, Cancer Research UK Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK [2] Department of Renal Medicine, Lincoln Wing, St James's University Hospital, Leeds, UK.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Welberry Smith
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zougman
authors.forename: David A
authors.initials: DA
authors.lastname: Cairns
authors.forename: Michelle
authors.initials: M
authors.lastname: Wilson
authors.forename: Tobias
authors.initials: T
authors.lastname: Wind
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wood
authors.forename: Douglas
authors.initials: D
authors.lastname: Thompson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Messenger
authors.forename: Andrew
authors.initials: A
authors.lastname: Mooney
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Selby
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: Lewington
authors.forename: Rosamonde E
authors.initials: RE
authors.lastname: Banks
mesh_terms: D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood / Q000201:enzymology / Q000209:etiology* / Q000628:therapy; D018572:Disease-Free Survival; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D006435:Renal Dialysis; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D003404:Creatinine; D000581:Amidohydrolases; C019672:aminoacylase I