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

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.

SUBMITTER: Lubetzky M

PROVIDER: S-EPMC7454827 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Lubetzky Michelle M Aull Meredith J MJ Craig-Schapiro Rebecca R Lee John R JR Marku-Podvorica Jehona J Salinas Thalia T Gingras Laura L Lee Jun B JB Sultan Samuel S Kodiyanplakkal Rosy Priya RP Hartono Choli C Saal Stuart S Muthukumar Thangamani T Kapur Sandip S Suthanthiran Manikkam M Dadhania Darshana M DM

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20200701 7

<h4>Background</h4>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.<h4>Methods</h4>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 fro ...[more]

PMID: 32678882

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Project description:Background and aimsAs conversion from calcineurin inhibitor to sirolimus (SRL), a mechanistic target of rapamycin inhibitor (mTOR-I), has been shown to enhance immunoregulatory profiles in liver transplant (LT) recipients (LTRs), mTOR-I therapy might allow for increased success of immunosuppression (IS) withdrawal. Our aim was to determine if operational tolerance could be observed in LTRs withdrawn from SRL and if blood/graft tolerance biomarkers were predictive of successful withdrawal.Approach and resultsWe performed a prospective trial of SRL monotherapy withdrawal in nonimmune, nonviremic LTRs > 3 years post-LT. SRL was weaned over ~6 months, and biopsies were performed 12 months postweaning or at concern for acute rejection. Twenty-one LTRs consented; 6 were excluded due to subclinical acute rejection on baseline biopsy or other reasons, and 15 underwent weaning (age 61.3 ± 8.8 years; LT to SRL weaning 6.7 ± 3 years). Eight (53%) achieved operational tolerance (TOL). Of the 7 who were nontolerant (non-TOL), 6 had mild acute rejection on biopsy near the end of weaning or at study end; 1 was removed from the trial due to liver cancer recurrence. At baseline preweaning, there were statistically increased blood tolerogenic dendritic cells and cell phenotypes correlating with chronic antigen presentation in the TOL versus non-TOL groups. A previously identified biopsy gene signature accurately predicted TOL versus non-TOL in 12/14 LTRs before weaning. At study end, biopsy staining revealed statistically significant increases in antigen-presenting cell:leukocyte pairings, FOXP3+ /CD4+ T cells, Tbet+ /CD8+ T cells, and lobular dendritic cells in the non-TOL group.ConclusionsThis study evaluated IS withdrawal directly from mTOR-I therapy in LTRs and achieved > 50% operational tolerance. Preweaning gene expression and peripheral blood mononuclear cell profiling may be useful as predictors of successful mTOR-I therapy withdrawal. NCT02062944.

Project description:Rationale & Objective:The world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. Study Design:All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. Setting & Participants:22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients. Results:Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n = 3), moderate (n = 8), extensive (n = 1), severe (n = 2), and critical (n = 1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died. Limitations:Small sample size and short follow-up. Conclusions:The clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.

Project description:BackgroundPrevious studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations.ObjectiveTo evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients.Design, setting, and participantsA total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group.InterventionImmunosuppressant reduction and low-dose methylprednisolone therapy.Outcome measurements and statistical analysisThe clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis.Results and limitationsThe clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4?±?9.3 vs 12.2?±?4.6 d in the control group) and a longer course of illness (35.3?±?8.3 vs 18.8?±?10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure.ConclusionsKidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations.Patient summaryImmunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.

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

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

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