BACKGROUND: Acute rejection (AR) is a strong predictor of renal graft survival, but the negative impact of AR on survival is variable, suggesting that other factors modulate this relationship. In this study, we examined the variables that correlate with graft survival after AR, particularly the impact of blood pressure (BP), graft function, and histopathology. METHODS: The study population included patients with no AR (N = 942) and patients with one (N = 407) or two (N = 156) AR during the first year post-transplant. Patients were adults who were recipients of living related (LRD, N = 410) or cadaveric grafts (CAD, N = 1095) and who were transplanted in a single institution and followed for 5.8 +/- 4 years. RESULTS: Compared with patients without AR, those with AR were significantly younger, had more human lymphocyte antigen mismatches, and included more CAD recipients. Graft survival was analyzed beyond six-months post-transplant. In patients with AR, reduced survival correlated (multivariate) with (a) younger recipients (P = 0.01), (b) AR occurring later during the first-year post-transplant (P = 0.0006), (c) elevated serum creatinine (Cr) before (P = 0.05), at the time (P = 0.0001) of, or after AR (P = 0.0004), and (d) average BP levels after AR [systolic BP (P = 0.003 logistic, P < 0.0001 by Cox), diastolic BP (P = 0.007), mean arterial pressure (P < 0.0001)]. This latter correlation was independent of graft function and recipient race. Thus, post-AR BP levels correlated with graft survival in patients with post-AR creatinine </=2 mg/dl (N = 408, P = 0.0009), in Caucasian recipients (P = 0.001), and in African American recipients (P = 0.01). In contrast, there was no significant correlation between BP levels and graft survival in patients without AR. AR histopathology, analyzed in patients with one AR episode, correlated with graft survival only the first six months after AR but not thereafter. CONCLUSIONS: Graft survival after AR can be predicted independently by graft function and BP levels after the event. Patients with elevated BP post-AR have poor graft survival even if they have excellent graft function.
BACKGROUND: Acute rejection (AR) is a strong predictor of renal graft survival, but the negative impact of AR on survival is variable, suggesting that other factors modulate this relationship. In this study, we examined the variables that correlate with graft survival after AR, particularly the impact of blood pressure (BP), graft function, and histopathology. METHODS: The study population included patients with no AR (N = 942) and patients with one (N = 407) or two (N = 156) AR during the first year post-transplant. Patients were adults who were recipients of living related (LRD, N = 410) or cadaveric grafts (CAD, N = 1095) and who were transplanted in a single institution and followed for 5.8 +/- 4 years. RESULTS: Compared with patients without AR, those with AR were significantly younger, had more human lymphocyte antigen mismatches, and included more CAD recipients. Graft survival was analyzed beyond six-months post-transplant. In patients with AR, reduced survival correlated (multivariate) with (a) younger recipients (P = 0.01), (b) AR occurring later during the first-year post-transplant (P = 0.0006), (c) elevated serum creatinine (Cr) before (P = 0.05), at the time (P = 0.0001) of, or after AR (P = 0.0004), and (d) average BP levels after AR [systolic BP (P = 0.003 logistic, P < 0.0001 by Cox), diastolic BP (P = 0.007), mean arterial pressure (P < 0.0001)]. This latter correlation was independent of graft function and recipient race. Thus, post-AR BP levels correlated with graft survival in patients with post-ARcreatinine </=2 mg/dl (N = 408, P = 0.0009), in Caucasian recipients (P = 0.001), and in African American recipients (P = 0.01). In contrast, there was no significant correlation between BP levels and graft survival in patients without AR. AR histopathology, analyzed in patients with one AR episode, correlated with graft survival only the first six months after AR but not thereafter. CONCLUSIONS: Graft survival after AR can be predicted independently by graft function and BP levels after the event. Patients with elevated BP post-AR have poor graft survival even if they have excellent graft function.
Authors: Daphne M Hullegie-Peelen; Marieke van der Zwan; Marian C Clahsen-van Groningen; Dana A M Mustafa; Sara J Baart; Marlies E J Reinders; Carla C Baan; Dennis A Hesselink Journal: Clin Pharmacol Ther Date: 2022-03-08 Impact factor: 6.903