The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19

以霉酚酸酯为基础的免疫抑制治疗方案与 COVID-19 肾移植患者死亡率增加有关

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作者:Lúcio R Requião-Moura, Luís Gustavo Modelli de Andrade, Tainá Veras de Sandes-Freitas, Marina Pontello Cristelli, Laila Almeida Viana, Mônica Rika Nakamura, Valter Duro Garcia, Roberto Ceratti Manfro, Denise Rodrigues Simão, Ricardo Augusto Monteiro de Barros Almeida, Gustavo Fernandes Ferreira, Kel

Background

The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes.

Conclusions

This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Methods

This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed.

Results

Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. Conclusions: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

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