title: Plasma procalcitonin is an independent predictor of graft failure late after renal transplantation.
abstract: BACKGROUND
  Chronic low-grade inflammation is involved in chronic transplant dysfunction after renal transplantation. Procalcitonin (PCT), known to reflect microbial inflammation, may also reflect ongoing noninfectious chronic low-grade inflammation in organ parenchyma, including transplanted kidneys. We aimed to compare predictive performance of plasma PCT for development of graft failure in renal transplant recipients (RTR) with that of high-sensitivity C-reactive protein (hsCRP), an established marker of systemic chronic low-grade inflammation.
  
  
  METHODS
  We included 575 RTR with functioning grafts for more than or equal to 1 year at a median (interquartile range) time of 6.1 (2.9-11.7) years posttransplant. PCT was determined using an ultrasensitive immunoluminometric assay and hsCRP using high-sensitivity enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Median (interquartile range) plasma PCT and hsCRP concentrations were 0.023 (0.017-0.036) ng/mL and 2.1 (0.8-4.9) mg/L, respectively. After a median (interquartile range) of 5.2 (4.5-5.7) years of follow-up, incidence of graft failure was 0.5%, 2.6%, and 18.5% according to increasing PCT tertiles (P<0.001 by log-rank test). Area under the curve of receiver operating characteristic analysis of PCT for prediction of graft failure was significantly higher than that of hsCRP (0.84 vs. 0.56, P<0.001). After adjustment for potential confounders, PCT remained an independent predictor of graft failure (hazard ratio=2.3 [95% confidence interval 1.4-3.7] per doubling PCT, P=0.0004), whereas this was not the case for hsCRP.
  
  
  CONCLUSIONS
  We identified plasma PCT as a strong and an independent predictor of graft failure in RTR. These data suggest that PCT in RTR reflects ongoing inflammation in parenchyma of transplanted kidneys. Further studies are required to investigate whether PCT could be of use as an early biomarker for chronic transplant dysfunction.
authors.affiliation: Department of Internal Medicine, Renal Transplant Program, University Medical Center Groningen and University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Rutger M
authors.initials: RM
authors.lastname: van Ree
authors.forename: Aiko P J
authors.initials: AP
authors.lastname: de Vries
authors.forename: Leendert H
authors.initials: LH
authors.lastname: Oterdoom
authors.forename: Marc A
authors.initials: MA
authors.lastname: Seelen
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Jan P
authors.initials: JP
authors.lastname: Schouten
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Reinold O B
authors.initials: RO
authors.lastname: Gans
authors.forename: Jaap J Homan
authors.initials: JJ
authors.lastname: van der Heide
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Son
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000453:epidemiology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000502:physiology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors; D017211:Treatment Failure
chemical_list: C000606589:CALCA protein, human; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide