mTOR-Inhibition and COVID-19 in Kidney Transplant Recipients: Focus on Pulmonary Fibrosis

Kidney transplant recipients are at high risk of developing severe COVID-19 due to the coexistence of several transplant-related comorbidities (e.g., cardiovascular disease, diabetes) and chronic immunosuppression. As a consequence, a large part of SARS-CoV-2 infected patients have been managed with a reduction of immunosuppression. The mTOR-I, together with antimetabolites, have been often discontinued in order to minimize the risk of pulmonary toxicity and to antagonize pharmacological interaction with antiviral/anti-inflammatory drugs. However, at our opinion, this therapeutic strategy, although justified in kidney transplant recipients with severe COVID-19, should be carefully evaluated in asymptomatic/paucisymptomatic patients in order to avoid the onset of acute allograft rejections, to potentially exploit the mTOR-I antiviral properties, to reduce proliferation of conventional T lymphocytes (which could mitigate the cytokine storm) and to preserve Treg growth/activity which could reduce the risk of progression to severe disease. In this review, we discuss the current literature regarding the therapeutic potential of mTOR-Is in kidney transplant recipients with COVID-19 with a focus on pulmonary fibrosis.

Download Full-text

Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York

Journal of the American Society of Nephrology ◽

10.1681/asn.2020030375 ◽

2020 ◽

Vol 31 (6) ◽

pp. 1150-1156 ◽

Cited By ~ 80

Author(s):

Keyword(s):

New York ◽

Kidney Transplant ◽

Severe Disease ◽

Treatment Protocol ◽

Current Treatment ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Radiographic Findings ◽

Increased Risk

BackgroundThe novel SARS-CoV-2 virus has caused a global pandemic of coronavirus disease 2019 (COVID-19). Although immunosuppressed individuals are thought to be at an increased risk of severe disease, little is known about their clinical presentation, disease course, or outcomes.MethodsWe report 15 kidney transplant recipients from the Columbia University kidney transplant program who required hospitalization for confirmed COVID-19, and describe their management, clinical course, and outcomes.ResultsPatients presented most often with a fever (87%) and/or cough (67%). Initial chest x-ray most commonly showed bilateral infiltrates, but 33% had no acute radiographic findings. Patients were managed with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin. Although 27% of our patients needed mechanical ventilation, over half were discharged home by the end of follow-up.ConclusionsKidney transplant recipients with COVID-19 have presentations that are similar to that of the general population. Our current treatment protocol appears to be associated with favorable outcomes, but longer follow-up of a larger cohort of patients is needed.

Download Full-text

mTOR inhibition in kidney transplant recipients

Nature Reviews Nephrology ◽

10.1038/nrneph.2011.125 ◽

2011 ◽

Vol 7 (10) ◽

pp. 553-555 ◽

Cited By ~ 7

Author(s):

Sarah E. Yost ◽

Rochelle Byrne ◽

Bruce Kaplan

Keyword(s):

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mtor Inhibition

Download Full-text

mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction

Aging ◽

10.18632/aging.202863 ◽

2021 ◽

Vol 13 (6) ◽

pp. 8026-8039

Author(s):

Barbara Infante ◽

Francesco Bellanti ◽

Michele Correale ◽

Paola Pontrelli ◽

Rossana Franzin ◽

...

Keyword(s):

Kidney Transplant ◽

Transplant Recipients ◽

Graft Dysfunction ◽

Kidney Transplant Recipients ◽

Mtor Inhibition ◽

Chronic Graft Dysfunction ◽

Cardiovascular Aging

Download Full-text

Renal allograft function in kidney transplant recipients infected with SARS-CoV 2: An academic single center experience

PLoS ONE ◽

10.1371/journal.pone.0252979 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252979

Author(s):

Skylar L. Nahi ◽

Aneesha A. Shetty ◽

Sajal D. Tanna ◽

Joseph R. Leventhal

Keyword(s):

Kidney Transplant ◽

Renal Allograft ◽

Severe Disease ◽

Kidney Injury ◽

Transplant Recipients ◽

Single Center ◽

Kidney Transplant Recipients ◽

P Values ◽

Mild Disease ◽

Allograft Function

Background Kidney transplant recipients are a unique cohort in regard to SARS-CoV 2 susceptibility and clinical course, owing to their immunosuppressed state and propensity for kidney injury. The primary purpose of this study is to ascertain if, in kidney transplant recipients, SARS-CoV 2 infection impacts long term renal allograft function. Methods This retrospective, single-center study reviewed 53 kidney transplant recipients with a positive SARS-CoV-2 PCR at NMH from January 1, 2020 to June 30, 2020. Results Change in eGFR from baseline kidney function prior to infection to 90 days after the first positive SARS-CoV 2 test was +1.76%, -17.5% and -23.16% the mild, moderate and severe disease groups respectively. There was a significant decline in kidney function in the moderate and severe disease cohorts as compared to the mild disease cohort, with respective p values of p = 0.0002 and p = 0.021. Relative to the mild disease cohort, the moderate and severe disease cohorts also demonstrated significantly increased risk of developing AKI (66%, 85%), both with p values of P = 0.0001. Conclusions Clinically severe SARS-CoV 2 infection is associated with greater risk of acute kidney injury and greater decline in renal allograft function at 90 days post infection, compared to mild disease.

Download Full-text

Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: A systematic review of a globally representative sample

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2020-0034 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Irtiza Hasan ◽

Tasnuva Rashid ◽

Sarah Suliman ◽

Hatem Amer ◽

Razvan M.Chirila ◽

...

Keyword(s):

Systematic Review ◽

Kidney Transplant ◽

Disease Severity ◽

Severe Disease ◽

Disease Outcome ◽

High Dose ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Aggregated Data

AbstractIntroduction: COVID-19 presents a special challenge to the kidney transplant population.Methods: A systematic review of articles that examined COVID-19 in kidney transplant recipients was performed. Patients’ demographics, clinical, laboratory and radiological presentations, immunosuppression modification, and COVID-19 specific management were abstracted and analyzed. COVID-19 severity was classified into mild, moderate, and severe. Disease outcome was classified by whether the patient was discharged, still hospitalized, or died.Results: 44 articles reporting individual data and 13 articles reporting aggregated data on 149 and 561 kidney transplant recipients respectively with COVID-19 from Asia, Europe and America fulfilled all inclusion and exclusion criteria. Among studies reporting case specific data, 76% of cases had severe disease. Compared to patients with mild/moderate disease, patients with severe disease had higher CRP, LDH, Ferritin, D-dimer and were more likely to have bilateral lung involvement at presentation and longer time since transplantation (P<0.05 for all). Recipients’ age, gender and comorbidities did not impact disease severity. Patients with severe disease had a more aggressive CNI reduction and more antiviral medications utilization. Outcome was reported on 145 cases, of those 34 (23%) died all with severe disease. Longer duration from transplant to disease diagnosis, hypoxia and higher LDH were associated with mortality (P<0.05). Different immunosuppression reduction strategies, high dose parenteral corticosteroids use and various antiviral combinations did not demonstrate survival advantage. Similar finding was observed for studies reporting aggregated data.Conclusion: COVID-19 in kidney transplant patients is associated with high rate of disease severity and fatality. Higher LDH and longer time since transplantation predicted both disease severity and mortality. None of the COVID-19 specific treatment correlated with, or improved disease outcome in kidney transplant recipients.

Download Full-text