Background Single case series suggested that RTx in AAV complicated by end-stage renal disease (ESRD) is safe and effective for graft and AAV outcome. Limited data are available with respect to predictors of increased risk of AAV relapse following RTx.
Objectives To investigate the outcomes of AAV patients who underwent RTx and the factors predictive of subsequent AAV relapse.
Methods Patients with AAV who had undergone RTx for AAV-related ESRD between 1994 and 2013 were identified from 7 RTx centers in the greater Paris area of France. Medical charts were retrospectively reviewed for demographic and AAV characteristics, pre- and post-RTx immunosuppressive therapy, AAV relapse and overall and graft survival. Episodes of acute rejection and renal AAV relapses were defined from renal graft biopsy findings. Survival and cumulative incidence rates were calculated by Kaplan-Meier analysis. Log rank analyses were used to study the risk of renal AAV relapses associated with factors assessed at the time of RTx (age, AAV and ANCA phenotype, pre-RTx cyclophosphamide [CYC] therapy).
Results We analyzed 46 patients (24 males [52%]) with AAV, including 9 (20%) with granulomatosis with polyangiitis (GPA), 13 (28%) microscopic polyangiitis (MPA) and 24 (52%) renal-limited vasculitis (RLV); ANCA specificities were PR3-ANCA in 12 (26%), MPO-ANCA in 29 (63%) and unknown in 5 (11%). Mean (SD) age at RTx was 40.7 (19.7) years; 10 (22%) underwent RTx during childhood (age<18 yr). Forty-two patients (91%) received CYC before RTx. The 10-year cumulative incidence of acute rejection episodes was 38%; 9 (20%) patients returned to dialysis and 3 (7%) underwent a second RTx. After a mean (SD) follow-up of 7.5 (5.2) years, renal AAV relapses were identified in 6 (13%) patients (10-year cumulative renal relapse incidence: 16%). No extra-renal AAV relapse was recorded and 1 (2%) patient died (10-year overall survival rate: 97%). The risk of renal AAV relapses was increased for patients who underwent RTx during childhood (hazard ratio [HR]: 5.7, P=0.01), with detectable ANCA at RTx (HR: 4.4, P=0.008) and in CYC-naive patients (HR: 11.6, P=0.0002) but was not linked with the GPA/MPA vs RLV phenotype (HR: 1.7, P=0.36) and MPO- vs PR3-ANCA specificity (HR: 2.2, P=0.46).
Conclusions The current outcomes of AAV patients undergoing RTx are favorable. Lack of pre-RTx CYC therapy and detectable ANCA at RTx may predict increased risk of renal AAV relapses. The increased AAV relapses in RTx during childhood may reflect lower adherence to anti-rejection therapy.
Disclosure of Interest None declared