Early Remdesivir Tied to Reduced Graft Loss and Cardiovascular Events in Kidney Transplant Recipients With Acute COVID-19
核心洞察
Early remdesivir treatment within 7 days of SARS-CoV-2 (搜索) diagnosis was associated with reduced risks for all-cause graft loss (HR = 0.53; 95% CI, 0.31-0.92) and cardiovascular events (HR = 0.58; 95% CI, 0.35-0.98) up to 1 year in kidney transplant recipients.
The retrospective cohort study, published in JAMA Network Open, emulated a target trial using data from 177 early remdesivir recipients and 255 untreated recipients across five Johns Hopkins Health System hospitals from 2020 to 2024.
Weighted analysis was deemed more appropriate than unweighted analysis, which had shown increased risks due to confounding by indication, as treated patients were older and sicker at baseline.
Early treatment with the antiviral remdesivir within 7 days of a positive SARS-CoV-2 (搜索) diagnosis was associated with reduced risks for all-cause graft loss and cardiovascular events up to 1 year in kidney transplant recipients with acute COVID-19 (搜索), according to a retrospective cohort study published in JAMA Network Open.
Kidney transplant recipients face particularly high risks for severe COVID-19 (搜索) due to comorbidities, receipt of immunosuppressive medications, and other factors, according to Nitipong (Nate) Permpalung, MD, MPH, FIDSA, associate director for clinical trials at the Johns Hopkins Transplant Research Center, and colleagues. "Previous studies in kidney transplant recipients have reported persistent allograft dysfunction and graft loss after COVID-19 in a subset of patients, particularly following severe illness or among patients who already had impaired graft function before infection," Permpalung told Healio. "Acute kidney injury may resolve, but recovery is not always complete."
Study Design and Patient Population
The researchers conducted a retrospective cohort study designed to emulate a target trial, assessing whether treatment with remdesivir (Veklury, Gilead Sciences) within 7 days of a positive SARS-CoV-2 (搜索) diagnosis could impact clinical outcomes for kidney transplant recipients.
The analysis included 177 kidney transplant recipients who received early remdesivir (median age, 61 years; 57.1% men) and 255 transplant recipients who did not receive remdesivir (median age, 54 years; 57.6% men) at five hospitals in the Johns Hopkins Health System between 2020 and 2024. Patients were followed for up to 1 year after diagnosis.
The primary outcome was all-cause graft loss, defined as graft failure and all-cause mortality. Secondary outcomes assessed all-cause mortality, cardiovascular events, and long COVID prevalence. Unweighted and weighted analyses were conducted to account for confounding by indication, according to Permpalung.
Confounding by Indication and the Weighted Analysis
The two treatment groups differed substantially at baseline. "Patients who received early remdesivir were older, nearly three times as likely to require supplemental oxygen at diagnosis and had higher prevalences of diabetes, hypertension, coronary artery disease and recent transplantation," Permpalung said. "The weighted analysis was designed to make the treatment strategies more comparable."
In the unweighted analysis, early remdesivir was associated with greater risks for all-cause graft loss (HR = 1.78; 95% CI, 1.01-3.13) and mortality (HR = 2.53; 95% CI, 1.27-5.01) after 1 year. In the weighted analysis, however, early remdesivir was associated with reduced risks for all-cause graft loss (HR = 0.53; 95% CI, 0.31-0.92) and cardiovascular events (HR = 0.58; 95% CI, 0.35-0.98).
"This substantial change between the unweighted and weighted estimates suggests that the crude comparison was strongly affected by differences in who received treatment," Permpalung said. "Hence, we consider the weighted analysis to be the more appropriate estimate for our prespecified target trial question."
Subgroup Findings
In the weighted model, early remdesivir, compared with no remdesivir, was associated with reduced risks for all-cause graft loss across several subgroups, including patients younger than 65 years (HR = 0.38; 95% CI, 0.16-0.87), those who received a deceased donor kidney (HR = 0.49; 95% CI, 0.26-0.95) or a living donor kidney (HR = 0.38; 95% CI, 0.16-0.94), those with a BMI greater than 30 kg/m² (HR = 0.32; 95% CI, 0.14-0.72), those with hypertension (HR = 0.58; 95% CI, 0.34-0.99), and those without known coronary artery disease (HR = 0.41; 95% CI, 0.21-0.8).
Clinical Implications and Proposed Mechanism
Overall, the results suggest antiviral treatment with remdesivir may provide protective benefits for the kidney allograft and cardiovascular health of kidney transplant recipients with acute COVID-19 (搜索) up to 1 year, according to the researchers.
"COVID-19 (搜索) in a kidney transplant recipient should prompt early assessment rather than waiting to see whether the illness becomes severe," Permpalung said. "Remdesivir is an important treatment option, but the choice of antiviral should be individualized according to the duration of symptoms, the patient's risk of progression, current clinical status, relevant drug interactions, safety considerations, patient preferences and the feasibility of receiving three consecutive intravenous infusions."
The researchers noted that potential mechanisms linking antiviral treatment to kidney allograft outcomes should be explored in future research. "A plausible explanation is that early suppression of viral replication reduces progression to severe COVID-19 (搜索) and then reduces acute kidney injury, low oxygen levels, systemic inflammation, vascular injury, thrombosis and other forms of cardiorenal stress," Permpalung said. "Better preservation of kidney function during the acute illness could then translate into better longer-term allograft outcomes, but that mechanism still needs to be tested."