title: Cyclosporin exposure correlates with 1 year graft function and histological damage in renal transplanted patients.
abstract: BACKGROUND
  Cyclosporin (CsA) level obtained 2 h after the morning dose (C(2)) has been shown to accurately predict total CsA exposure and acute rejection (AR) risk, whereas conventional trough levels (C(0)) do not. The impact of C(2) monitoring on long-term kidney graft function, independent from AR risk, is still unclear, however, and it was assessed in the present study.
  
  
  METHODS
  We enrolled 39 CsA-treated renal transplant recipients and used 1 year graft function and histological structure as surrogate markers of graft outcome. CsA dose was adjusted according to C(2) levels.
  
  
  RESULTS
  In the first 7 days after grafting, 40-51% of patients failed to reach target C(2) levels; nevertheless, at 1 year the incidence of AR was only 2.5% and graft and patient survival was 100%. The decrease of serum creatinine (12-6 months) was associated with significantly higher C(2) levels over time (P = 0.0003) and lower intrapatient variability of CsA relative absorption (CV) (P = 0.0006). One year graft biopsy showed chronic tubulointerstitial lesions in 54.5% of patients. Both C(2) mean levels and the percentage CV independently predicted the severity of chronic histological lesions (R = 0.69, P<0.0001).
  
  
  CONCLUSIONS
  Higher C(2) levels, within the proposed target range values, seem to be associated with better renal function and structure.
authors.affiliation: Department of Emergency and Organ Transplant, Division of Nephrology, University of Bari, Policlinico, Piazza Giulio Cesare 11, I-70124 Bari, Italy. s.dipaolo@nephro.uniba.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: di Paolo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Teutonico
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Barbara
authors.initials: B
authors.lastname: Infante
authors.forename: Antonio
authors.initials: A
authors.lastname: Schena
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ditonno
authors.forename: Paolo F
authors.initials: PF
authors.lastname: Schena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D011184:Postoperative Period; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine