title: Can an increased nitric oxide level be accepted as non-invasive marker for sub/acute rejection of the kidney allograft?
abstract: BACKGROUND
  Subclinical and acute rejections (SAR/AR) continue to have a negative impact on graft survival. The aim of our study was to analyze allograft rejection and nitric oxide (NO) levels in patients with protocol- and clinically-indicated biopsies in relationship with other causes of allograft dysfunction, and to evaluate the clinical impact of NO measurement as non-invasive marker for early diagnosis of SAR/AR.
  
  
  METHODS
  In 45 living-related kidney transplants, serum NO levels were measured at: 20 min after reperfusion (NO1); on days 1 (NO2), 5 (NO3), and 14 (NO4); and at the first (NO5) and sixth (NO6) months after transplantation (Tx). Protocol biopsies (Bx) were performed at the first and sixth months after Tx.
  
  
  RESULTS
  38 (42.2%) Bx showed histological features of (SAR), 4 (4.5%) Bx showed mild tubulointerstitial rejection, while 48 (53.3%) Bx had no histological signs of SAR/AR. Significantly higher (NO3) levels were found in patients with AR and (NO5)/(NO6) in SAR as compared to other causes of allograft dysfunction occurred within the first posttransplant month (delayed graft function, urinary tract infection, and cyclosporine toxicity). Sensitivity/specificity for cut-off NO level of 70 μmol/l were 69.2% and 88.4% in AR, and 78.9% and 75.4% for the level of 50 μmol/l in SAR patients, respectively.
  
  
  CONCLUSIONS
  Our study reports significantly higher serum NO levels at day 5 and a gradual decrease at day 14 (prior to and at the time of clinically manifested AR), and at 1- and 6-month protocol biopsies in SAR patients as compared to all other causes of renal dysfunction. NO measurement may have a satisfactorily diagnostic performance as a useful non-invasive marker not only for AR, but also for SAR patients.
authors.affiliation: Department of Nephrology, Faculty of Medicine, University of Skopje - Macedonia.
authors.forename: Jelka
authors.initials: J
authors.lastname: Masin-Spasovska
authors.forename: Saso
authors.initials: S
authors.lastname: Dohcev
authors.forename: Oliver
authors.initials: O
authors.lastname: Stankov
authors.forename: Sotir
authors.initials: S
authors.lastname: Stavridis
authors.forename: Skender
authors.initials: S
authors.lastname: Saidi
authors.forename: Beti
authors.initials: B
authors.lastname: Dejanova
authors.forename: Petar
authors.initials: P
authors.lastname: Dejanov
authors.forename: Anita
authors.initials: A
authors.lastname: Hristova-Dimceva
authors.forename: Koco
authors.initials: K
authors.lastname: Dimitrovski
authors.forename: Goce
authors.initials: G
authors.lastname: Spasovski
mesh_terms: D000208:Acute Disease; D000368:Aged; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide