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How to use COVID-19 antiviral drugs in patients with chronic kidney disease.

ABSTRACT: Antiviral drugs such as Remdesivir (Veklury), Nirmatrelvir with Ritonavir (Paxlovid), Azvudine, and Molnupiravir (Lagevrio) can reduce the risk for severe and fatal Coronavirus Disease (COVID)-19. Although chronic kidney disease is a highly prevalent risk factor for severe and fatal COVID-19, most clinical trials with these drugs excluded patients with impaired kidney function. Advanced CKD is associated with a state of secondary immunodeficiency (SIDKD), which increases the susceptibility to severe COVID-19, COVID-19 complications, and the risk of hospitalization and mortality among COVID-19 patients. The risk to develop COVID-19 related acute kidney injury is higher in patients with precedent CKD. Selecting appropriate therapies for COVID-19 patients with impaired kidney function is a challenge for healthcare professionals. Here, we discuss the pharmacokinetics and pharmacodynamics of COVID-19-related antiviral drugs with a focus on their potential use and dosing in COVID-19 patients with different stages of CKD. Additionally, we describe the adverse effects and precautions to be taken into account when using these antivirals in COVID-19 patients with CKD. Lastly, we also discuss about the use of monoclonal antibodies in COVID-19 patients with kidney disease and related complications.

SUBMITTER: Kale A

PROVIDER: S-EPMC9947246 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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How to use COVID-19 antiviral drugs in patients with chronic kidney disease.

Kale Ajinath A Shelke Vishwadeep V Dagar Neha N Anders Hans-Joachim HJ Gaikwad Anil Bhanudas AB

Frontiers in pharmacology 20230209

Antiviral drugs such as Remdesivir (Veklury), Nirmatrelvir with Ritonavir (Paxlovid), Azvudine, and Molnupiravir (Lagevrio) can reduce the risk for severe and fatal Coronavirus Disease (COVID)-19. Although chronic kidney disease is a highly prevalent risk factor for severe and fatal COVID-19, most clinical trials with these drugs excluded patients with impaired kidney function. Advanced CKD is associated with a state of secondary immunodeficiency (SIDKD), which increases the susceptibility to se ...[more]

PMID: 36843922

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Project description:BackgroundPatients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse.MethodsPatients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates.ResultsOf 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups.ConclusionsIn a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.

Project description:BackgroundA population-based study would be useful to identify the association between chronic kidney disease (CKD) or acute kidney injury (AKI) and prognosis of coronavirus disease 2019 (COVID-19) patients.MethodsThis retrospective study utilized the claim data from Korea. Patients who underwent COVID-19 testing and were confirmed to be positive were included and divided into the following three groups based on the presence of CKD or requirement of maintenance dialysis: Non-CKD (participants without CKD), non-dialysis CKD (ND-CKD), and dialysis-dependent CKD (DD-CKD) patients. We collected data on the development of severe clinical outcomes and death during follow-up. Severe clinical outcomes were defined as the use of inotropics, conventional oxygen therapy, high-flow nasal cannula, mechanical ventilation, or extracorporeal membrane oxygenation and the development of AKI, cardiac arrest, myocardial infarction, or acute heart failure after the diagnosis of COVID-19. AKI was defined as the initiation of renal replacement therapy after the diagnosis of COVID-19 in patients not requiring maintenance dialysis. Death was evaluated according to survival at the end of follow-up.ResultsAltogether, 7,341 patients were included. The median duration of data collection was 19 (interquartile range, 11-28) days. On multivariate analyses, odds ratio (OR) for severe clinical outcomes in the ND-CKD group was 0.88 (95% confidence interval [CI], 0.64-1.20; P = 0.422) compared to the Non-CKD group. The DD-CKD group had ORs of 7.32 (95% CI, 2.14-33.90; P = 0.004) and 8.32 (95% CI, 2.37-39.21; P = 0.002) compared to the Non-CKD and ND-CKD groups, respectively. Hazard ratio (HR) for death in the ND-CKD group was 0.79 (95% CI, 0.49-1.26; P = 0.318) compared to the Non-CKD group. The DD-CKD group had HRs of 2.96 (95% CI, 1.09-8.06; P = 0.033) and 3.77 (95% CI, 1.29-11.06; P = 0.016) compared to the Non-CKD and ND-CKD groups, respectively. DD-CKD alone was associated with severe clinical outcomes and higher mortality. There was no significant difference in frequency of severe clinical outcomes or mortality rates between the Non-CKD and ND-CKD groups. In patients not requiring maintenance dialysis, AKI was associated with old age, male sex, and high Charlson's comorbidity index score but not with the presence of CKD. HRs for patients with AKI were 11.26 (95% CI, 7.26-17.45; P < 0.001) compared to those for patients without AKI in the multivariate analysis. AKI was associated with severe clinical outcomes and patient survival, rather than underlying CKD.ConclusionCKD requiring dialysis is associated with severe clinical outcomes and mortality in patients with COVID-19; however, the development of AKI is more strongly associated with severe clinical outcomes and mortality.

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How to use COVID-19 antiviral drugs in patients with chronic kidney disease.

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How to use COVID-19 antiviral drugs in patients with chronic kidney disease.

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