Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy.

Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID-19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID-19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33-year-old man with end-stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4-month protocol visit. He was diagnosed with COVID-19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4-month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody-mediated rejection (ABMR). Donor-specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin-converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR.

Better outcome of COVID-19 positive kidney transplant recipients during the unremitting stage with optimized anticoagulation and immunosuppression.

INTRODUCTION: COVID-19 is an ongoing pandemic with high morbidity and mortality and with a reported high risk of severe disease in kidney transplant recipients (KTR). AIM: We aimed to report the largest number of COVID-19-positive cases in KTR in a single center and to discuss their demographics, management, and evolution. METHODS: We enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID-19-positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes. RESULTS: Out of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty-two of them needed hospitalization, of which thirty-one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow-up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%. CONCLUSION: Better outcome of COVID-19-positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.

Favorable outcome of COVID-19 among African American (AA) renal transplant recipients in Detroit.

Transplant recipients are vulnerable to infections, including COVID-19, given their comorbidities and chronic immunosuppression. In this study, all hospitalized renal transplant recipients (RTR) with a positive nasal swab for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2) seen consecutively between 03/01/2020 and 05/01/2020 at the Detroit Medical Center were included. Data on demographics, clinical presentation, laboratory findings, management, and outcomes were collected. Twenty-five patients were included, all African American (AA) and deceased-donor transplant recipients. The most common presenting symptom was dyspnea, followed by fever, cough and diarrhea. Multifocal opacities on initial chest x-ray were seen in 52% patients and 44% of patients had a presenting oxygen saturation of less than or equal to 94%. Four patients (16%) required transfer to the intensive care unit, one required intubation and one expired. COVID-19-infected RTR in this cohort had low mortality of 4% (n = 1). Despite multiple comorbidities and chronic immunosuppression, our cohort of African American RTR had favorable outcomes compared to other reports on COVID-19 in RTR.

Kidney transplant patients with SARS-CoV-2 infection: The Brescia Renal COVID task force experience.

The outcome of kidney transplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. Here we describe the clinical characteristics, disease outcome, and risk factors for acute respiratory distress syndrome (ARDS) and death of a cohort of 53 kidney transplant patients with coronavirus disease 2019 (COVID-19). Eight of 53 have been handled as outpatients because of mild disease, on average with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS, or died. Because of severe symptoms, 45/53 required admission: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/d, hydroxychloroquine, and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. About 33% of the patients developed acute kidney injury, 60% ARDS, and 33% died. In this group, thrombocytopenia was associated to ARDS whereas lymphopenia at the baseline, higher D-dimer, and lack of C-reactive protein reduction were associated with risk of death. In the overall population, dyspnea was associated with the risk of ARDS and age older than 60 years and dyspnea were associated with the risk of death with only a trend toward an increased risk of death for patients on tacrolimus. In conclusion, SARS-CoV-2 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission.

Should cyclosporine be useful in renal transplant recipients affected by SARS-CoV-2?

Minimization of immunosuppression and administration of antiretrovirals have been recommended for kidney transplant recipients (KTRs) with coronavirus disease 2019 (COVID-19). However, outcomes remain poor. Given the likely benefit of cyclosporine because of its antiviral and immunomodulatory effect, we have been using it as a strategy in KTRs diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied 29 kidney transplant recipients (KTRs) who were admitted to our institution with COVID-19 between March 15and April, 24, 2020. Mycophenolate and/or mammalian target of rapamycin inhibitors (mTORi) were discontinued in all patients. Two therapeutic strategies were compared: Group 1, minimization of calcineurin inhibitors (N = 6); and Group 2, cyclosporine-based therapy (N = 23), with 15 patients switched from tacrolimus. Hydroxychloroquine was considered in both strategies but antivirals in none. Six patients died after respiratory distress (20.6%). Five required mechanical ventilation (17.2%), and 3 could be weaned. Nineteen patients had an uneventful recovery (65.5%). In group 1, 3 of 6 patients died (50%) and 1 of 6 required invasive mechanical ventilation (16.7%). In group 2, 3 of 23 patients died (12.5%). Renal function did not deteriorate and signs of rejection were not observed in any patient on the second treatment regime. In conclusion, immunosuppressant treatment based on cyclosporine could be safe and effective for KTRs diagnosed with COVID-19.