Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19

Abstract

On May 1, 2020, after review of yet unpublished data from available clinical trials, the US Food and Drug Administration issued an emergency use authorization (EUA) to permit the use of remdesivir, a nucleotide analog that inhibits viral RNA-dependent RNA polymerase (RDRP), for treatment of adults and children hospitalized with severe coronavirus disease 2019 (COVID-19). EUA was granted after an interim analysis of 606 recoveries in the randomized, placebo-controlled National Institute of Allergy and Infectious Diseases Adaptive Covid-19 Treatment Trial (n51063 participants from 47 United States sites and 21 international sites). Remdesivir reduced the median time to recovery (11 versus 15 days; hazard ratio, 1.31; 95% confidence interval, 1.12 to 1.54; P,0.001) compared with placebo, and overall mortality among patients treated with remdesivir was 8.0% compared with 11.6% among those treated with placebo (P50.59). 1 Notably, patients with severe AKI and ESKD were excluded from this and all other remdesivir trials on the basis of eGFR cutoffs (either 50 or 30 ml/ min per 1.73 m 2 ) (Table 1). As a result, the EUA fact sheet for health care providers states the following. 1

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States

“…These discussions are particularly germane for individuals with kidney disease because remdesivir, one of the few 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 728 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 813 814 815 816 818 819 820 821 822 825 826 827 828 829 830 831 832 833 834 835 836 837 838 839 840 evidence-based COVID-19 therapeutic options currently available, is generally not recommended for adults with eGFR < 30 mL/min/1.73 m 2 . 39 However, the purported risks of remdesivir in the setting of decreased eGFR that stem from concerns related to accumulation of its carrier, sulfobutylether-β-cyclodextrin, may be overstated. 39 Moreover, individuals with decreased kidney function are being excluded from clinical trials of other potential therapeutic agents (eg, favipiravir [Clinicaltrials.gov identifier NCT04358549 40 ]).…”

“…39 However, the purported risks of remdesivir in the setting of decreased eGFR that stem from concerns related to accumulation of its carrier, sulfobutylether-β-cyclodextrin, may be overstated. 39 Moreover, individuals with decreased kidney function are being excluded from clinical trials of other potential therapeutic agents (eg, favipiravir [Clinicaltrials.gov identifier NCT04358549 40 ]). Such exclusions may represent yet another example of "renalism" and deserve healthy skepticism by the nephrology community.…”

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study

“…NED, no evidence of disease. 956 (44) 559 (26) 671 (31) 1115 (51) 334 (15) 476 (22) 200 (9) 1011 (46) 597 (27) 275 (13) 303 (14) 705 (32) 643 (29) 1258 (58) 471 (22) 709 (32) 389 (18) 1781 81470 (22) 749 (34) 563 (26) 352 (16) 1115 (51) 607 (28) 239 (11) 1037 47…”

Approaching coronavirus disease 2019: Mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2

“…Remdesvir is usually well-tolerated for short courses. However, concerns were raised about its potential toxicity in patients with kidney dysfunction, related not only to the drug-mediated injury of renal tubular epithelial cells, but also to the nephrotoxicity associated with the drug vehicle (i.e., sulfobutylether-β-cyclodextrin) required for the intravenous formulation [124].…”