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Renal Disease and COVID-19
COVID-19 Antiviral Use in Patients With Renal Dysfunction

Released: October 21, 2022

Expiration: October 20, 2023

Lynora Saxinger
Lynora Saxinger, MD, FRCPC, CTropMed
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Key Takeaways:

  • Patients with chronic kidney disease have an increased risk of hospitalization and mortality due to COVID-19 infection.
  • It is imperative to test for COVID-19 infection and treat this vulnerable group.

There is considerable evidence that individuals with chronic kidney disease have an increased risk of hospitalization and mortality due to COVID-19 infection, highlighting the need to test and treat these vulnerable patients in a timely manner. However, patients with advanced chronic kidney disease were not included in clinical trials (and therefore are excluded from many use guidelines) of the currently available SARS-CoV-2 antiviral medications, including nirmatrelvir plus ritonavir, remdesivir, and molnupiravir.

Fortunately, some data are emerging.

Nirmatrelvir Plus Ritonavir
Although patients with advanced chronic kidney disease were not included in outpatient nirmatrelvir plus ritonavir COVID-19 trials, pharmacokinetic data support dose adjustments to enable treatment of these high-risk patients, with one group suggesting a 300-mg dose on Day 1 followed by 150 mg daily for 4 days (after hemodialysis on dialysis days).

Because ritonavir is a CYP3A4 inhibitor, careful review of patients’ other medications—such as statins, calcium channel blockers, and direct-acting oral anticoagulants—is important, although it is often possible to hold, dose reduce, or substitute medications to allow nirmatrelvir plus ritonavir use for COVID-19.

However, patients with renal disease who are receiving calcineurin inhibitors, mycophenolic acid, or sirolimus post transplant or to treat autoimmune diseases are at higher risk of difficult drug interactions and may require specialist and pharmacist consultation.

Guidelines appear to be evolving, with the National Institutes of Health and WHO COVID guidelines not recommending treatments for patients with an estimated glomerular filtration rate (eGFR) <30 mL/min until more data are available, whereas several guidelines and nephrology expert groups suggest dose-adjusted nirmatrelvir plus ritonavir in these patients.

Remdesivir

Remdesivir was not originally recommended for patients with an eGFR <30 mL/min due to concerns of accumulation of the renally excreted excipient SBECD with potential toxicity risk. However, the exposure in a course of remdesivir is lower than the safety threshold dose of the European Medicines Agency and significant toxicity in a several day course is felt unlikely. In this context of risk of poor outcomes from severe COVID-19, the benefits of remdesivir treatment may outweigh the risks in those with low eGFR, and we do have some data to review.

Accordingly, the CATCO trial allowed discretionary use of remdesivir without dose adjustment in patients with renal insufficiency. In this trial, remdesivir was used for hospitalized patients with moderate to severe COVID-19, a group expected to have a higher risk of renal complications than those receiving remdesivir for its high-risk ambulatory patient indication. Investigators reported on 59 such patients with a baseline eGFR <30 mL/min/1.73 m2, although most were not on dialysis. There was no increased risk of adverse renal or hepatic effects at Day 5 and no need for mechanical ventilation or dialysis, or occurrence of mortality. This makes sense because we would expect that any potential accumulative toxicity risks would be lower with a shorter treatment course in early infection.

Finally, a separate observational study of 486 patients on dialysis hospitalized with COVID-19 suggested that remdesivir recipients trended to lower 30-day mortality, liver injury, and ICU admission rates.

Based on data like these, the National Institutes of Health COVID-19 guidelines suggest that remdesivir can be used in patients with an eGFR <30 mL/min if the potential benefits outweigh the risks.

Molnupiravir
Molnupiravir is an alternative antiviral agent recommended for use by the National Institutes of Health COVID-19 treatment guidelines when nirmatrelvir plus ritonavir or remdesivir are either unavailable or not appropriate for use in an individual patient. Studies of molnupiravir also excluded patients with severe renal dysfunction (eGFR >30 mL/min/1.73 m2), but the Emergency Use Authorization states that severe renal impairment or end-stage renal disease are not expected to have a significant impact on drug exposure. For patients with an eGFR >30 mL/min/1.73 m2, no renal dose adjustments are necessary. Molnupiravir is not for use in pregnancy and reliable contraception is recommended for males for 3 months after use.

Conclusion
Patients with chronic kidney disease are a vulnerable group at high risk of COVID-19 infection and poor outcomes when infected. There currently are more clinical data on the use of IV remdesivir in this patient population, although this area is evolving rapidly, and dose-adjusted nirmatrelvir plus ritonavir is recommended by some groups, with further data anticipated. Current pharmacologic and safety evidence supports an approach of informed consent and detailed risk–benefit assessment to support the use of COVID-19 antivirals in people with chronic kidney disease.

Your Thoughts?
What antivirals do you prescribe for your patients with COVID-19 and chronic kidney disease? Join the discussion by posting a comment below.