Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center

  1. Michelle Lubetzky
  2. Meredith J Aull
  3. Rebecca Craig-Schapiro
  4. John R Lee
  5. Jehona Marku-Podvorica
  6. Thalia Salinas
  7. Laura Gingras
  8. Jun B Lee
  9. Samuel Sultan
  10. Rosy Priya Kodiyanplakkal
  11. Choli Hartono
  12. Stuart Saal
  13. Thangamani Muthukumar
  14. Sandip Kapur
  15. Manikkam Suthanthiran
  16. Darshana M Dadhania

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Abstract

Background

Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies.

Methods

We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate.

Results

Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients.

Conclusions

Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.

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  1. Version published to 10.1093/ndt/gfaa154
  2. ScreenIT

    SciScore for 10.1101/2020.04.30.20086462: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Our review was covered by our Weill Cornell Medicine Institutional Review Board approved protocol #
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations of this study that must be considered include the small sample size. Additionally, due to limitations in Covid-19 testing capabilities in New York, we were unable to test all patients with symptoms and thus the number of infected transplant patients is likely much higher. Since remdesivir or IL-6 receptor antagonist was not given in a systematic fashion in our study, we will have to wait for the results from the controlled trials to understand their effectiveness. Yet it is important to note that many transplant patients may not be eligible for such studies which is why careful review of single center data will be an integral piece to understand how best to treat SARS-Cov-2 infections in kidney transplant recipients. In sum, using a coordinated and multidisciplinary approach, the patients with mild symptoms, were successfully managed as outpatients with close monitoring for symptom progression and with minimal reductions in immunosuppressive agents. For hospitalized patients, careful evaluation and judicious reduction in immunosuppressive drugs and prompt treatment of secondary bacterial infections, were associated with a low case fatality rate. We did however observe significant AKI in a substantial percentage of hospitalized patients. A therapeutic strategy of clinical severity dependent reduction rather than complete withdrawal of immunosuppressive drug therapy appears reasonable for kidney allograft recipients diagnosed with Covid-19.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.04.30.20086462v2 on medRxiv
  4. Version published to 10.1101/2020.04.30.20086462v1 on medRxiv