ABSTRACT
De novo thrombotic microangiopathy (dnTMA), after renal transplantation may significantly alter graft outcomes. However, its pathogenesis and the role of complement alternative pathway dysregulation remain elusive. We studied all consecutive adult patients with a kidney allograft biopsy performed between January 2004 and March 2016 displaying dnTMA. Ninety-two patients were included. The median time of occurrence was 166 (IQR 25-811) days. The majority (82.6 %) had TMA localized only in the graft. Calcineurin inhibitor toxicity and antibody-mediated rejection (ABMR) were the 2 most frequent causes (54.3% and 37.0%, respectively). However, etiological factors were multiple in 37% patients. Interestingly, pathogenic variants in the genes of complement alternative pathway were significantly more frequent in the 42 tested patients than in healthy controls (16.7% vs 3.7% respectively, P < .008). The overall graft survival after biopsy was 66.0% at 5 years and 23.4% at 10 years, significantly worse than a matched cohort without TMA. Moreover, graft survival of patients with TMA and ABMR was worse than a matched cohort with ABMR without TMA. The 2 main prognostic factors were a positive C4d staining and a lower estimated glomerular filtration rate at diagnosis. DnTMA is a severe and multifactorial disease, induced by 1 or several endothelium-insulting conditions, mostly calcineurin inhibitor toxicity and ABMR.
ABSTRACT
Background: Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis. Methods: We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment. Results: We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up. Conclusions: This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule.
