Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients

Abstract

This analysis, using data from the Brazilian kidney transplant (KT) COVID‐19 study, seeks to develop a prediction score to assist in COVID‐19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28‐day fatality after the COVID‐19 diagnosis, assessed by the area under the ROC curve (AUC‐ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28‐day fatality rate was 17% ( n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID‐19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC‐ROC of 0.767 (95% CI 0.698–0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non‐hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.

Predictors of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Patients: Baseline Characteristics, Immunosuppression, and the Role of IMPDH Monitoring

“…As expected, several patient characteristics have an impact on the serological response after vaccination: older patients, more recently grafted patients, and those with poorer kidney graft function are at a higher risk of non-response. Age and lower GFR were also predictive of fatal outcomes in a Brazilian cohort used to establish a tool for the early prediction of COVID-19-associated death after kidney transplantation [ 26 ], and immunosenescence likely played a role in both observations [ 27 ]. Beyond patient age, the intensity of early immunosuppression with high rates of triple immunosuppression, higher MPA exposure, higher CNI trough levels, and various induction regimens with monoclonal or polyclonal antibodies (data not shown) favored non-response to vaccination.…”

The Higher COVID-19 Fatality Rate Among Kidney Transplant Recipients Calls for Further Action

“…1,2 Even higher fatality rates were observed in kidney transplant recipients, probably because of their impaired immune response because of the long-term use of immunosuppressive drugs, in addition to the high prevalence of comorbidities such as diabetes and cardiovascular diseases. 3,4…”

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

“…In a cohort study, the risk of death among liver transplant recipients was 4-fold higher in those using mycophenolate. 30 Another cohort recently published by our group showed that mTORi (versus MPA or AZA) was protective for death within 30 d. 22 Some clinical trials evaluating the effect of mTORi on COVID-19 are ongoing. Interestingly, other mTOR inhibitors beyond sirolimus and everolimus have been considered promising for inhibiting COVID-19 infection.…”

“… 21 Nevertheless, in our previous preliminary analysis, although the use of MPA was associated with increased risk, the use of mTORi was associated with reduced risk of COVID-19–associated death. 22 Thus far, data on the impact of immunosuppressive regimens on COVID-19–clinical outcomes are lacking. Therefore, the present study seeks to compare COVID-19–associated outcomes among KTRs receiving calcineurin inhibitor (Cni) in combination with AZA, MPA, or mTORi.…”