“COVID-19 Tanısı Almış Kronik Böbrek Hastalarında Favipiravir Tedavisinin Laboratuvar Parametreleri Üzerindeki Etkisinin Değerlendirilmesi'': Retrospektif Tek Merkezli Bir Çalışma

Abstract

Amaç: Başlangıçta influenza için geliştirilen favipiravir, COVID-19 için potansiyel bir tedavi seçeneğidir. Ancak kronik böbrek yetmezliği olan hastalarda favipiravirin güvenlilik verileri sınırlıdır. Bu çalışma, renal fonksiyon bozukluğunun oluşturduğu zorlukları göz önünde bulundurarak, kronik böbrek hastalığı (KBH) olan ve olmayan COVID-19 hastalarında favipiravirin laboratuvar parametreleri üzerindeki etkilerini incelemeyi amaçlamıştır. Gereç ve Yöntemler: Bu retrospektif çalışmada, Türkiye’de bir üçüncü basamak hastanede izlenen, başlangıçta 559 katılımcı arasından seçilen ve PCR pozitif olan 339 uygun COVID-19 yatan hasta incelenmiştir. Hastalar, tahmini glomerüler filtrasyon hızına (eGFR) göre <60 mL/dk/1,73 m² ve ≥60 mL/dk/1,73 m² (kontrol grubu) olmak üzere iki gruba ayrılmıştır. Klinik, demografik ve laboratuvar özellikleri parametrik ve nonparametrik testler kullanılarak karşılaştırılmış, istatistiksel anlamlılık düzeyi p<0,05 olarak kabul edilmiştir. Bulgular: Favipiravir ile ilişkili akut böbrek hasarı, ürik asit yükselmesi, nötropeni veya aspartat aminotransferaz (AST) artışı açısından gruplar arasında anlamlı fark saptanmamıştır (sırasıyla p=0,137; p=0,653; p=0,326; p=0,135). Alanin aminotransferaz (ALT) artışı kontrol grubunda orta düzeyde anlamlı bulunmuştur (p=0,001). Hipertansiyon, koroner arter hastalığı, konjestif kalp yetmezliği ve malignite gibi komorbiditeler kronik böbrek hastalığı grubunda anlamlı derecede daha yüksek bulunmuştur (p<0,001); ancak mortalite oranları açısından gruplar arasında anlamlı fark saptanmamıştır (p=0,519). Sonuç: Favipiravir tedavisi, kronik böbrek hastalığı olan hastalarda renal parametreler üzerinde anlamlı bir etki göstermemiştir. Bununla birlikte, alanin aminotransferaz (ALT) ve aspartat aminotransferaz (AST) düzeylerinde hafif artışlar gözlenmiş olup, bu durum hastalık şiddeti ve diğer katkıda bulunan faktörlerle ilişkili olabilir. Uygun laboratuvar değerlendirmeleri ile hepatik fonksiyonlar yakından izlenmek koşuluyla, favipiravir kronik böbrek hastalığı olan hastalarda güvenle kullanılabilir.

Keywords

• COVID-19
• favipiravir
• kronik böbrek hastalığı
• hepatotoksisite

“Evaluation of The Impact of Favipiravir Therapy on Laboratory Parameters in Patients with Chronic Kidney Disease Diagnosed with COVID-19” : A Retrospective Sin- gle Centre Study

Abstract

Aim: Favipiravir, initially developed for influenza, is a potential treatment for COVID-19. However, safety data for favipiravir in patients with chronic renal failure is limited. This study examined its effects on laboratory parameters in COVID-19 patients both with and without chronic kidney disease (CKD), addressing the challenges posed by renal health impairment. Material and Methods: This retrospective study examined 339 eligible PCR-positive COVID-19 inpatients, selected from an initial 559 participants, at a Turkish tertiary care hospital. The patients were grouped based on estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and ≥ 60 mL/min/1.73 m² (control group). Clinical, demographic, and laboratory characteristics were compared using parametric and nonparametric tests, with statistical significance set at p<0.05. Results: No significant differences were observed between the groups for favipiravir-associated acute kidney injury, uric acid elevation, neutropenia, or aspartate aminotransferase elevation (p=0.137, p=0.653, p=0.326, p=0.135). Alanine aminotransferase elevation was moderately significant in the control group (p=0.001). Comorbidities, including hypertension, coronary artery disease, congestive heart failure, and malignancy, were significantly higher in the chronic kidney disease group (p<0.001), but mortality rates did not differ significantly (p=0.519). Conclusion: Favipiravir treatment did not significantly affect renal parameters in patients with chronic kidney disease. However, mild increases in alanine aminotransferase and aspartate aminotransferase levels were noted, which may be linked to disease severity and other contributing factors. Favipiravir can be safely given to patients with chronic kidney disease as long as hepatic function is closely monitored through appropriate laboratory assessments.

Keywords

• COVİD-19
• favipiravir
• chronic kidney disease
• hepatotoxicity

References

1. Du YX, Chen XP. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection. Clin Pharmacol Ther. 2020;108(2):242-247.
2. Ghasemnejad-Berenji M, Pashapour S. Favipiravir and COVID-19: A Simplified Summary. Drug Res. 2020;71(03):166-170.
3. Fujii S, Ibe Y, Ishigo T, et al. Early favipiravir treatment was associated with early defervescence in non-severe COVID-19 patients. J Infect Chemother. 2021;27(7):1051-1057. doi:10.1016/j.jiac.2021.04.013
4. Gil-Martínez V, Salas AA, Ballestín SS. Antiviral Therapeutic Approaches for SARS-CoV-2 Infection: A Systematic Review. Pharmaceuticals. 2021;14(8):736.
5. Kaptein S, Jacobs S, Langendries L, et al. Favipiravir at High Doses Has Potent Antiviral Activity in SARS-CoV-2−infected Hamsters, Whereas Hydroxychloroquine Lacks Activity. Proc Natl Acad Sci. 2020;117(43):26955-26965.
6. Gök S, Bahçecíoğlu ÖF, Durmuş M, et al. The Safety Profile of Favipiravir in COVID-19 Patients With Severe Renal Impairment. Int J Clin Pract. 2021;75(12).
7. Yadigar S, Parmaksız E, Dincer MT, et al. The efficacy of favipiravir treatment in hemodialysis patients with COVID 19. Journal of Clinical Images and Medical Case Reports. 2022;3(5).
8. https://covid19.saglik.gov.tr/TR-66393/covid-19-salgin-yonetimi-ve-calisma rehberi.html. Accessed at 19.12.2024.

9. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines [Internet]. Bethesda (MD): National Institutes of Health (US); 2021 Apr 21-2024 Mar 1. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570371/Accessed at 19.12.2024.
10. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):117-314.
11. National Cancer Institute (NCI). (2017). Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0). U.S. Department of Health and Human Services, National Institutes of Health. Accessed at 19.12.2024.
12. Sürmelioğlu N, Demirtürk E, Ayhan NA, et al. Favipiravir pharmacokinetics in COVID-19 patients with moderate to severe kidney dysfunction: Lessons learned for future use. International Journal of Clinical Pharmacology and Therapeutics. 2024;62(08):345-352.
13. Hanai Y, Yoshizawa S, Matsuo K, et al. Evaluation of risk factors for uric acid elevation in COVID-19 patients treated with favipiravir. Diagnostic Microbiology and Infectious Disease. 2022;102(4):115640.
14. Kaya B, Atas DB, Tigen ET, et al. Favipiravir Use in Kidney Transplant Recipients with COVID-19: A Single-Center Experience. Experimental and Clinical Transplantation. 2022;20(2):143-149.
15. Yaylaci S, Dheir H, Şenocak D, et al. The effects of favipiravir on hematological parameters of covid-19 patients [published correction appears in Rev Assoc Med Bras (1992). 2020 Oct;66(10):1463. doi: 10.1590/1806-9282.66.10.1463]. Rev Assoc Med Bras (1992). 2020;66Suppl 2(Suppl 2):65-70.
16. Ozudogru O, Yerlikaya E, Alayunt NO, Zafer A. Evaluation of favipiravir treatment before intensive care in COVID-19 patients. Jurnal Teknologi Laboratorium. 2021;10(1):22-30.
17. Bayram M, Yildirim O, Ozmen R, et al. Elevation of Serum Transaminase Levels Due to Favipiravir Use in the Treatment of COVID-19. Cureus. 2021;13(9):e18166.
18. Ergür FÖ, Yıldız M, Şener MU, et al. Adverse effects associated with favipiravir in patients with COVID-19 pneumonia: a retrospective study. Sao Paulo Med J. 2022;140(3):372-377.
19. Hasmono D, Arta NAF, Ismawati N, et al. Study of effectiveness and side effects of favipiravir therapy on mild and moderate covid-19 patients. Jurnal Kesehatan. 2022;15(2):108-120.