title: Early Kidney Allograft Dysfunction (Threatened Allograft): Comparative Effectiveness of Continuing Versus Discontinuation of Tacrolimus and Use of Sirolimus to Prevent Graft Failure: A Retrospective Patient-Centered Outcome Study.
abstract: BACKGROUND
  Due to lack of treatment options for early acute allograft dysfunction in the presence of tubular-interstitial injury without histological features of rejection, kidney transplant recipients are often treated with sirolimus-based therapy to prevent cumulative calcineurin inhibitor exposure and to prevent premature graft failure.
  
  
  METHODS
  We analyzed transplant recipients treated with sirolimus-based (n = 220) compared with continued tacrolimus-based (n = 276) immunosuppression in recipients of early-onset graft dysfunction (threatened allograft) with the use of propensity score-based inverse probability treatment weighted models to balance for potential confounding by indication between 2 nonrandomized groups.
  
  
  RESULTS
  Weighted odds for death-censored graft failure (odds ratio [OR], 1.20; 95% confidence interval [95% CI], 0.66-2.19,P= 0.555) was similar in the 2 groups, but a trend for increased risk of greater than 50% loss in estimated glomerular filtration rate from baseline in sirolimus group (OR, 1.90; 95% CI, 0.96-3.76;P= 0.067) compared with tacrolimus group. Sirloimus group compared with tacrolimus group had increased risk for death with functioning graft (OR, 2.01; 95% CI, 1.29-3.14;P= 0.002) as well as increased risk of late death (death after graft failure while on dialysis) (OR, 2.39; 95% CI, 1.59-3.59;P< 0.001). Analysis of subgroups based on the absence or presence of T cell-mediated rejection or tubulointerstitial inflammation in the index biopsy, or the use of different types of induction agents, and all subgroups had increased risk of death with functioning graft and late death if exposed to sirolimus-based therapy.
  
  
  CONCLUSIONS
  Use of sirolimus compared with tacrolimus in recipients with early allograft dysfunction during the first year of transplant may not prevent worsening of allograft function and could potentially lead to poor survival along with increased risk of late death.
authors: Transplant Division, Department of Surgery and Medicine, Inova Health System. Falls Church, VA.
authors: Ravinder K
authors: RK
authors: Wali
authors: Transplant Division, Department of Surgery and Medicine, Inova Health System. Falls Church, VA.
authors: Heather A
authors: HA
authors: Prentice
authors: Division of Nephrology, Department of Medicine, University Of Maryland School of Medicine, Baltimore, MD.
authors: Venkata
authors: V
authors: Reddivari
authors: Division of Nephrology, Department of Medicine, University Of Maryland School of Medicine, Baltimore, MD.
authors: Geroge
authors: G
authors: Baffoe-Bonnie
authors: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
authors: Cinthia I
authors: CI
authors: Drachenberg
authors: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
authors: John C
authors: JC
authors: Pappadimitriou
authors: Division of Nephrology, Department of Medicine, University Of Maryland School of Medicine, Baltimore, MD.
authors: Emilio
authors: E
authors: Ramos
authors: Department of Transplant Surgery, University of Maryland School of Medicine, Baltimore, MD.
authors: Matthew
authors: M
authors: Cooper
authors: Transplant Division, Department of Surgery and Medicine, Inova Health System. Falls Church, VA.
authors: Johann
authors: J
authors: Jonsson
authors: Department of Transplant Surgery, University of Maryland School of Medicine, Baltimore, MD.
authors: Stephen
authors: S
authors: Bartlett
authors: Division of Nephrology, Department of Medicine, University Of Maryland School of Medicine, Baltimore, MD.
authors: Matthew R
authors: MR
authors: Weir