key: cord-0960889-zqls095y
authors: Vásquez-Jiménez, Enzo; Moguel-González, Bernardo; Soto-Abraham, Virgilia; Flores-Gama, César
title: Risk of acute rejection in kidney transplant recipients after COVID-19
date: 2021-11-17
journal: J Nephrol
DOI: 10.1007/s40620-021-01192-x
sha: 5e0a860d701bf709d2f5fd8933a7743ff184b94a
doc_id: 960889
cord_uid: zqls095y

nan

Detection and characterization of anti-HLA antibodies were performed using Single Antigen Flow Beads assays (LSA class I and class II, Immucor, Norcross, GA). Luminex mean fluorescence intensity (MFI) was measured on a LABscan IS 200, specificities with an MFI ≥ 1000 were considered positive. De novo DSAs (dnDSAs) were considered positive when they had not been identified pre-transplantation. Kidney biopsy was planned 4 weeks after COVID-19 diagnosis, however, some biopsies had to be deferred. All biopsies were analyzed by a single expert kidney pathologist. Histological lesions were classified according to The Banff 2019 Kidney Meeting Report [5] .

The baseline characteristics of kidney recipients are shown in Table 1 . The details concerning clinical presentation are shown in Table S1 . In our center, immunosuppressive treatment was decreased or withdrawn in 60% of patients, and excluding 3 cases, all patients had returned to their usual immunosuppressive regimen at the time of biopsy. We did not find a different pattern of immunosuppressive regimen modification in patients with and without rejection (67 vs 57%, P = 0.33).

Thirty percent of patients had no major abnormalities in their kidney biopsy, 20% had chronic active antibodymediated rejection (ABMR), 15% active ABMR, 20% mixed ABMR/ T cell mediated rejection (TCMR), 10% borderline for acute TCMR, and 5% chronic active TCMR (Table S2 ). All patients who developed dnDSAs (n = 11) were diagnosed with rejection, 27.2% with ABMR, 36.4% mixed ABMR/ TCMR and 36.4% with chronic ABMR.

Among cases diagnosed with rejection, 57% were considered subclinical. Subclinical rejection was diagnosed in all cases borderline for active TCMR and active ABMR, in 50% of active chronic ABMR, and in 25% of mixed ABMR/ TCMR, while all TCMR and 16.7% of biopsies with no major abnormalities had persistent kidney injury at biopsy. A detailed description is available in Tables 2 and S3.

We found that 70% of patients who recovered from COVID-19 had signs of acute rejection in the kidney graft biopsy. This high rate of biopsy-proven signs of rejection, almost half of which are classified as subclinical rejections, is a matter of concern. In a cohort of 47 kidney transplant recipients with immunosuppression minimization for COVID-19, Pampols et al. reported that none developed dnDSAs; however, allograft biopsies were not performed [6] .

Six of our patients had a history of acute rejection, in 3 of them the allograft biopsy revealed chronic active ABMR, which may be the evolution of the previous rejection. However, even excluding these patients, biopsy revealed active rejection in 9 patients without a history of rejection. It is possible that dnDSAs were present before the COVID-19 diagnosis, however 25% of acute rejection type 2 were diagnosed within 12 months after transplantation, increasing the chance that dnDSAs were developed close to COVID-19. As for adherence to immunosuppressive treatment during the SARS-CoV-2 pandemic, Aziz et al. reported on kidney recipients without a diagnosis of COVID-19 who developed acute rejection during the COVID-19 pandemic due to non-adherence and loss to follow-up [7] . This possibility cannot be ruled out in our series.

Our analysis is preliminary, and the lack of serial biopsies and dnDSAs tests does not allow drawing cause-effect conclusions; however, within these limits, our findings suggest that COVID-19-related immunologic challenge, together with the reduction of immunosuppresion may trigger kidney transplant rejection; this should be a warning to transplant centers to monitor allograft dysfunction. Nonetheless, stable serum creatinine after COVID-19 infection does not exclude ongoing damage to the graft, therefore, a kidney 

Acute kidney injury in COVID-19: emerging evidence of a distinct pathophysiology

Acute kidney injury in critically ill patients with COVID-19

Coronavirus disease 2019: implications of emerging infections for transplantation

A systematic review of COVID-19 and kidney transplantation

The banff 2019 kidney meeting report (I): updates on and clarification of criteria for T cell-and antibody-mediated rejection

Immunosuppression minimization in kidney transplant recipients hospitalized for COVID-19

Unusually high rates of acute rejection during the COVID-19 pandemic: cause for concern?

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

Acknowledgements We thank the Nephrology medical staff from the National Institute of Cardiology.

The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s40620-021-01192-x.