Brandacher, Gerald

Background. Chronic kidney disease (CKD) is a common complication of nonrenal transplantation, influencing recipients’ morbidity and mortality. The incidence of CKD varies depending on the transplanted organ. Recipients of vascularized composite allotransplantation (VCA) need lifelong immunosuppression similar to that of solid organ transplantation. This study investigated renal function in VCA recipients. Methods. We studied 70 recipients from 17 centers (median follow-up: 8 y): 59 upper extremity, 10 face, and 1 penis transplant. Pretransplant and posttransplant clinical data and sera were collected to calculate the estimated glomerular filtration rate (eGFR) using the CKD Epidemiology collaboration 2021 formula. Results. Pretransplantation, the median eGFR was 105.36 mL/min (range, 71.39–155.39 mL/min). By 3 mo posttransplant, the eGFR had significantly decreased to 78.42 mL/min (range, 32.49–130.74 mL/min; P = 0.001) before stabilizing. Despite higher tacrolimus levels at 3 mo, no correlation with eGFR was found. During follow-up, 17.1% of patients experienced a ≥50% eGFR decline, 10.9% progressed to CKD, and 4.7% developed end-stage kidney disease. Some risk factors were identified, but their responsibility could not be established with certainty because of the low number of severe renal outcomes. Conclusions. Renal function declines in the majority of VCA recipients, but the function loss is lower compared with nonrenal solid organ transplantation recipients. Although no statistically significant correlation could be established between tacrolimus exposure and renal function decline, strategies aiming at minimizing calcineurin inhibitor exposure and avoiding other nephrotoxic causes are recommended to preserve long-term kidney function.

Objectives: This report summarizes a collaborative effort between the American Society of Reconstructive Transplantation and the International Society of Vascularized Composite Allotransplantation to establish what is known about chronic rejection in recipients of vascularized composite allografts, with an emphasis on upper extremity and face transplants. As a picture of chronic rejection in hand and face vascularized composite allografts emerges, the results will be applied to other types of vascularized composite allografts, such as uterine transplantation. Methods: The overall goal is to develop a definition of chronic rejection in vascularized composite allografts so that we can establish longitudinal correlates of factors such as acute rejection, immunosuppressive therapy, de novo donor-specific antibody and trauma/infection and other external factors on the development of chronic rejection. As Dr Kanitakis eloquently stated at the 2017 International Society of Vascularized Composite Allotransplantation meeting in Salzburg, “Before we can correlate causative factors of chronic rejection, we have to define what chronic rejection in VCA is.” Results: The first meeting report was presented at the sixth Biennial meeting of the American Society of Reconstructive Transplantation in November 2018. Based on collaborative efforts and descriptions of clinical cases of chronic rejection in vascularized composite allograft recipients, a working definition of chronic rejection in vascularized composite allografts with respect to overt functional decline, subclinical functional decline, histologic evidence without functional decline, and normal allograft function in the absence of histologic evidence of chronic rejection is proposed. Conclusions: It is the intent of this collaborative working group that these working definitions will help to focus ongoing research to define the incidence, risk factors and treatment regimens that will identify mechanisms of chronic rejection in vascularized composite allografts. As with all good research, our initial efforts have generated more questions than answers. We hope that this is the first of many updates.