High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation

Abstract

ABSTRACT Introduction We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Methods Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991–2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4). Results Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5–2.5) vs 0.3 (0.1–0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. Conclusions One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.