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Impact of intensive dosing of mycophenolate on pancreas allograft survival.
Clinical Transplantation 2018 July
PURPOSE: To evaluate the effect of mycophenolate (mycophenolic acid, MPA) dose on pancreas allograft survival following simultaneous pancreas kidney (SPK) transplant.
METHODS: This was an observational study of adult SPK recipients transplanted between 1/1/2002 and 6/30/2015. Recipients were divided into cohorts based on MPA dose at discharge: high dose (HD), 1000 mg three times daily mycophenolate mofetil (MMF) and standard dose (SD), 1000 mg twice daily MMF. Primary outcome was pancreas allograft survival. Secondary endpoints included kidney allograft survival, pancreas allograft rejection, infection, time to initial dose decrease, and patient survival (PS).
RESULTS: In all, 453 patients met inclusion criteria: 324 in HD-MPA group and 129 in SD-MPA group. HD-MPA patients had higher rates of pancreas graft survival (P = .003). There were no differences in rates of pancreas allograft rejection (P = .8), kidney graft survival (P = .15), overall infection (P = .4), overall malignancy (P = .93), time to first dose reduction (P = .35), or patient survival (P = .3). In a multivariable analysis adjusted for differences between groups and known confounders, dosing group continued to significantly affect incidence of pancreas allograft failure (P = .02).
CONCLUSIONS: HD-MPA significantly impacted pancreas allograft survival in SPK recipients independent of graft rejection. Further studies are warranted to investigate the etiology of this finding and determine the optimal duration of HD-MPA associated with positive graft outcomes.
METHODS: This was an observational study of adult SPK recipients transplanted between 1/1/2002 and 6/30/2015. Recipients were divided into cohorts based on MPA dose at discharge: high dose (HD), 1000 mg three times daily mycophenolate mofetil (MMF) and standard dose (SD), 1000 mg twice daily MMF. Primary outcome was pancreas allograft survival. Secondary endpoints included kidney allograft survival, pancreas allograft rejection, infection, time to initial dose decrease, and patient survival (PS).
RESULTS: In all, 453 patients met inclusion criteria: 324 in HD-MPA group and 129 in SD-MPA group. HD-MPA patients had higher rates of pancreas graft survival (P = .003). There were no differences in rates of pancreas allograft rejection (P = .8), kidney graft survival (P = .15), overall infection (P = .4), overall malignancy (P = .93), time to first dose reduction (P = .35), or patient survival (P = .3). In a multivariable analysis adjusted for differences between groups and known confounders, dosing group continued to significantly affect incidence of pancreas allograft failure (P = .02).
CONCLUSIONS: HD-MPA significantly impacted pancreas allograft survival in SPK recipients independent of graft rejection. Further studies are warranted to investigate the etiology of this finding and determine the optimal duration of HD-MPA associated with positive graft outcomes.
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