The Effect of Nirmatrelvir-Ritonavir on Short- and Long-term Adverse Outcomes From COVID-19 Among Patients With Kidney Disease: A Propensity Score-Matched Study

Open Forum Infect Dis. 2024 Dec 31;12(1):ofae756. doi: 10.1093/ofid/ofae756. eCollection 2025 Jan.

Abstract

Background: Patients with kidney disease are at high risk for adverse outcomes after coronavirus disease 2019 (COVID-19) despite vaccination. Because patients with advanced chronic kidney disease (CKD) and kidney failure were excluded from registrational trials, the impact of the protease inhibitor nirmatrelvir-ritonavir in patients with kidney disease is unknown.

Methods: This was a cohort study evaluating adverse outcomes in patients with kidney disease who developed COVID-19. Patients prescribed nirmatrelvir-ritonavir for COVID-19 between March 16, 2022, and November 30, 2022, were propensity score-matched to comparators diagnosed with COVID-19 between July 15, 2021, and March 15, 2022 (before the use of nirmatrelvir-ritonavir in our health care network). We determined the association between nirmatrelvir-ritonavir and short- and long-term outcomes using Fine-Gray subdistribution hazard and Cox proportional hazard models, adjusting for potential confounders. Outcomes included 30-day risk of hospitalization and 1-year risk of a major adverse cardiovascular event (MACE), CKD progression, and death.

Results: A total of 1095 nirmatrelvir-ritonavir-treated patients were matched to 584 comparators. Patients who received nirmatrelvir-ritonavir patients were less likely to be hospitalized within 30 days of diagnosis (adjusted subdistribution hazard ratio [sHR], 0.44; 95% CI, 0.26-0.73; P < .01). At 1 year, nirmatrelvir-ritonavir-treated patients had a lower risk of hospitalization for MACE (adjusted sHR, 0.49; 95% CI, 0.36-0.67; P < .01) and death (adjusted hazard ratio, 0.37; 95% CI, 0.21-0.65; P < .01). Use of nirmatrelvir-ritonavir was not associated with decreased risk of CKD progression or attenuation of estimated glomerular filtration rate decline slope in the year following infection.

Conclusions: Nirmatrelvir-ritonavir was associated with decreased risk of hospitalization within 30 days and 1-year risk of MACE and death in patients with CKD and kidney failure.

Keywords: COVID-19; chronic kidney disease; major adverse cardiovascular event; nirmatrelvir-ritonavir.