The pattern, pharmacotherapy course, drug-drug interactions, and clinical outcome of COVID-19 in kidney transplant patients at a referral transplantation hospital in Iran: A retrospective, observational study

Document Type : Original Article

Authors

1 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Kidney transplant recipients are at higher risk of developing coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the pattern, pharmacotherapy, drug interactions, and clinical outcome of COVID-19 in kidney transplant recipients at a referral center in Iran. This retrospective, observational study was conducted in Abu Ali Sina Organ transplantation center in Shiraz, Iran. All adult kidney transplant patients diagnosed with COVID-19 and hospitalized for at least 48 hours were included. Required data were collected by reviewing medical charts and health information system of patients at hospital. Potential drug-drug interactions were identified using Lexi-Interact online as well as the Liverpool interactions online website. A total of 108 patients were included. Fever, cough, and shortness of breath were the most common clinical symptoms. About three-fourth (74%) of patients had non-severe COVID-19. Remdesivir was the most widely used antiviral agent. mTOR inhibitors and anti-metabolites were either dose reduced or discontinued in 100% and 80.2% of cases, respectively. Age (odds ratio [OR] = 1.06, 95% [Cl] = 1.02-1.09), calcineurin inhibitor adjustment (OR = 0.26, 95% Cl = 0.09-0.75), baseline white blood cell count (OR = 1.13, 95% Cl = 1.01-1.28), baseline serum lactate dehydrogenase level (OR = 1.32, 95% Cl = 1.03-1.69), administration of tocilizumab (OR = 0.06, 95% Cl = 0.07-0.54), and the severity of COVID-19 disease (OR = 0.03, 95% Cl = 0.00-0.03) had significant association with mortality.  The present investigation found that COVID-19 infection in kidney transplant patients may be severe and require hospitalization and even, critical care. 

Highlights

Mojtaba Shafiekhani (Google Scholar)

Iman Karimzadeh (Google Scholar)

Keywords

References

1.    Yang Y, Shang W, Rao X. Facing the COVID-19 outbreak: What should we know and what could we do? J Med Virol. 2020 Jun;92(6):536-537. doi: 10.1002/jmv.25720. Epub 2020 Mar 5. PMID: 32091134; PMCID: PMC7228352.
2.    Khodaei F, Ahsan A, Chamanifard M, Zamiri MJ, Ommati MM. Updated information on new coronavirus disease 2019 occurrence, drugs, and prediction of a potential receptor. J Biochem Mol Toxicol. 2020 Dec;34(12):e22594. doi: 10.1002/jbt.22594. Epub 2020 Aug 8. PMID: 32770858; PMCID: PMC7435514.
3.    Kordzadeh-Kermani E, Khalili H, Karimzadeh I. Pathogenesis, clinical manifestations and complications of coronavirus disease 2019 (COVID-19). Future Microbiol. 2020 Sep;15:1287-1305. doi: 10.2217/fmb-2020-0110. Epub 2020 Aug 27. PMID: 32851877; PMCID: PMC7493723.
4.    WHO COVID-19 dashboard. Available from: https://data.who.int/dashboards/covid19. (Accessed on January 12, 2025).
5.    Ritschl PV, Nevermann N, Wiering L, Wu HH, Moroder P, Brandl A, et al. Solid organ transplantation programs facing lack of empiric evidence in the COVID-19 pandemic: A By-proxy Society Recommendation Consensus approach. Am J Transplant. 2020 Jul;20(7):1826-1836. doi: 10.1111/ajt.15933. Epub 2020 May 10. PMID: 32323460; PMCID: PMC7264649.
6.    Caillard S, Thaunat O. COVID-19 vaccination in kidney transplant recipients. Nat Rev Nephrol. 2021 Dec;17(12):785-787. doi: 10.1038/s41581-021-00491-7. PMID: 34580488; PMCID: PMC8475856.
7.    Diao B, Wang C, Wang R, Feng Z, Zhang J, Yang H, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection. Nat Commun. 2021 May 4;12(1):2506. doi: 10.1038/s41467-021-22781-1. PMID: 33947851; PMCID: PMC8096808.
8.    López V, Vázquez T, Alonso-Titos J, Cabello M, Alonso A, Beneyto I, et al. Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients. Nefrologia (Engl Ed). 2020 May-Jun;40(3):265-271. English, Spanish. doi: 10.1016/j.nefro.2020.03.002.
9.    Kolla E, Weill A, Zaidan M, De Martin E, Colin De Verdiere S, Semenzato L, et al. COVID-19 Hospitalization in Solid Organ Transplant Recipients on Immunosuppressive Therapy. JAMA Netw Open. 2023 Nov 1;6(11):e2342006. doi: 10.1001/jamanetworkopen.2023.42006. PMID: 37934496; PMCID: PMC10630896.
10.    Abu Jawdeh BG, Vikram HR. Coronavirus Disease 2019 in Kidney Transplantation - A 2024 Update. Adv Kidney Dis Health. 2024 Sep;31(5):458-465. doi: 10.1053/j.akdh.2024.03.004. PMID: 39232616.
11.    Malek-Hosseini S, Razmkon A, Mehdizadeh A, Salahi H, Bahador A, Raiss-Jalali GH, et al. Long-term results of renal transplantation: A single-center analysis of 1200 transplants. Transplant Proc. 2006 Mar;38(2):454-6. doi: 10.1016/j.transproceed.2006.01.020. PMID: 16549145.
12.    Shafiekhani M, Shahabinezhad F, Niknam T, Tara SA, Haem E, Mardani P, et al. Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand? Virol J. 2021 Nov 22;18(1):228. doi: 10.1186/s12985-021-01700-2.
13.    Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349. Epub 2013 Mar 15. PMID: 23499048.
14.    Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust. 2020 Jul;213(2):54-56.e1. doi: 10.5694/mja2.50674. Epub 2020 Jun 22. PMID: 32572965; PMCID: PMC7361309.
15.    Levey AS, Stevens LA. Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis. 2010 Apr;55(4):622-7. doi: 10.1053/j.ajkd.2010.02.337. PMID: 20338463; PMCID: PMC2846308.
16.    Patel MK, Bergeri I, Bresee JS, Cowling BJ, Crowcroft NS, Fahmy K, et al. Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization. Vaccine. 2021 Jul 5;39(30):4013-4024. doi: 10.1016/j.vaccine.2021.05.099.
17.    Yamada G, Hayakawa K, Matsunaga N, Terada M, Suzuki S, Asai Y, et al. Predicting respiratory failure for COVID-19 patients in Japan: a simple clinical score for evaluating the need for hospitalisation. Epidemiol Infect. 2021 Jul 30;149:e175. doi: 10.1017/S0950268821001837. PMID: 36043382; PMCID: PMC8365048.
18.    Monfared A, Dashti-Khavidaki S, Jafari R, Jafari A, Ramezanzade E, Lebadi MK, et al. Clinical characteristics and outcome of COVID-19 pneumonia in kidney transplant recipients in Razi hospital, Rasht, Iran. Transpl Infect Dis. 2020 Dec;22(6):e13420. doi: 10.1111/tid.13420. Epub 2020 Aug 2. PMID: 32681756; PMCID: PMC7404381.
19.    Devresse A, Belkhir L, Vo B, Ghaye B, Scohy A, Kabamba B, et al. COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium. Kidney Med. 2020 Jun 15;2(4):459-466. doi: 10.1016/j.xkme.2020.06.001. PMID: 32775986; PMCID: PMC7295531.
20.    Akalin E, Azzi Y, Bartash R, Seethamraju H, Parides M, Hemmige V, et al. Covid-19 and Kidney Transplantation. N Engl J Med. 2020 Jun 18;382(25):2475-2477. doi: 10.1056/NEJMc2011117. Epub 2020 Apr 24. PMID: 32329975; PMCID: PMC7200055.
21.    Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. COVID-19 infection in kidney transplant recipients. Kidney Int. 2020 Jun;97(6):1076-1082. doi: 10.1016/j.kint.2020.03.018. Epub 2020 Apr 9. PMID: 32354637; PMCID: PMC7142878.
22.    Cravedi P, Mothi SS, Azzi Y, Haverly M, Farouk SS, Pérez-Sáez MJ, et al. COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium. Am J Transplant. 2020 Nov;20(11):3140-3148. doi: 10.1111/ajt.16185. Epub 2020 Aug 4. PMID: 32649791; PMCID: PMC7405285.
23.    Ahmadian E, Zununi Vahed S, Mammadova S, Abediazar S. Immunosuppressant Management in Renal Transplant Patients with COVID-19. Biomed Res Int. 2021 Oct 14;2021:9318725. doi: 10.1155/2021/9318725. PMID: 34692845; PMCID: PMC8531766.
24.    Samavat S, Nafar M, Firozan A, Pourrezagholi F, Ahmadpoor P, Samadian F, et al. COVID-19 Rapid Guideline in Kidney Transplant Recipients. Iran J Kidney Dis. 2020 May;14(3):231-234. PMID: 32361701.
25.    Rahimzadeh H, Keykhaei M, Razeghi E, Zivari E, Mansouri ES. COVID-19 progression in kidney transplant recipients: a single-center case series. CEN Case Rep. 2021 Nov;10(4):494-499. doi: 10.1007/s13730-021-00584-z. Epub 2021 Mar 26. PMID: 33770414; PMCID: PMC7994352.
26.    Abolghasemi S, Mardani M, Sali S, Honarvar N, Baziboroun M. COVID-19 and kidney transplant recipients. Transpl Infect Dis. 2020 Dec;22(6):e13413. doi: 10.1111/tid.13413. Epub 2020 Jul 31. PMID: 32677721; PMCID: PMC7404434.
27.    Shafiekhani M, Kazemi K, Bahador A, Imanieh MH, Karimzadeh P. Pediatric liver and kidney transplantation in the era of COVID-19: a follow-up study from a tertiary referral center in Iran. BMC Surg. 2021 May 11;21(1):240. doi: 10.1186/s12893-021-01226-y. PMID: 33975594; PMCID: PMC8112472.
28.    García-Rodríguez D, Remior P, García-Izquierdo E, Toquero J, Castro V, Fernández Lozano I. Drug-induced QT prolongation in COVID-19 pneumonia: influence on in-hospital survival. Rev Esp Cardiol (Engl Ed). 2021 Jan;74(1):111-112. doi: 10.1016/j.rec.2020.09.027. Epub 2020 Oct 29. PMID: 33172794; PMCID: PMC7598758.
29.    Ma BM, Hung IFN, Chan GCW, Tam AR, Chan SSK, Wong BCK, et al. Case of "relapsing" COVID-19 in a kidney transplant recipient. Nephrology (Carlton). 2020 Dec;25(12):933-936. doi: 10.1111/nep.13786. Epub 2020 Sep 28. PMID: 32951300; PMCID: PMC7536982.
30.    Toapanta N, Torres IB, Sellarés J, Chamoun B, Serón D, Moreso F. Kidney transplantation and COVID-19 renal and patient prognosis. Clin Kidney J. 2021 Mar 26;14(Suppl 1):i21-i29. doi: 10.1093/ckj/sfab030. PMID: 33815780; PMCID: PMC7995521.
31.    Dogas T, Brkovic T, Novak I, Radic J. COVID-19 in kidney transplant recipients; a DALMATIAN single-center experience. Ther Apher Dial. 2023 Feb;27(1):107-116. doi: 10.1111/1744-9987.13894. Epub 2022 Jun 19. PMID: 35684944; PMCID: PMC9347706.
32.    Pascual J, Melilli E, Jiménez-Martín C, González-Monte E, Zárraga S, Gutiérrez-Dalmau A, et al. COVID-19-related Mortality During the First 60 Days After Kidney Transplantation. Eur Urol. 2020 Oct;78(4):641-643. doi: 10.1016/j.eururo.2020.06.036. Epub 2020 Jun 19. PMID: 32624283; PMCID: PMC7303649.
33.    Coll E, Fernández-Ruiz M, Sánchez-Álvarez JE, Martínez-Fernández JR, Crespo M, Gayoso J, et al. COVID-19 in transplant recipients: The Spanish experience. Am J Transplant. 2021 May;21(5):1825-1837. doi: 10.1111/ajt.16369. Epub 2020 Nov 10. PMID: 33098200; PMCID: PMC9906239.
34.    Demir E, Ucar ZA, Dheir H, Danis R, Yelken B, Uyar M, et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol. 2022 May 12;23(1):183. doi: 10.1186/s12882-022-02784-w. PMID: 35550025; PMCID: PMC9097147.
35.    Schaenman J, Byford H, Grogan T, Motwani Y, Beaird OE, Kamath M, et al. Impact of solid organ transplant status on outcomes of hospitalized patients with COVID-19 infection. Transpl Infect Dis. 2022 Aug;24(4):e13853. doi: 10.1111/tid.13853. Epub 2022 Jun 13. PMID: 35579437; PMCID: PMC9347588.
36.    Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430-436. doi: 10.1038/s41586-020-2521-4. Epub 2020 Jul 8. PMID: 32640463; PMCID: PMC7611074.
37.    Navari Y, Bagheri AB, Akhavan Rezayat A, SeyedAlinaghi S, Najafi S, Barzegary A, et al. Mortality risk factors in kidney-transplanted patients with COVID-19: A systematic review and regression analysis. Health Sci Rep. 2021 Nov 4;4(4):e427. doi: 10.1002/hsr2.427. PMID: 34761124; PMCID: PMC8567748.
38.    Villanego F, Mazuecos A, Pérez-Flores IM, Moreso F, Andrés A, Jiménez-Martín C, et al. Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry. Am J Transplant. 2021 Jul;21(7):2573-2582. doi: 10.1111/ajt.16579. Epub 2021 Apr 12. PMID: 33756067; PMCID: PMC8250925.
39.    Carbajo-Lozoya J, Müller MA, Kallies S, Thiel V, Drosten C, von Brunn A. Corrigendum to 'Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506' Virus Research (2012) 165/1 [112-117]: Corrigendum. Virus Res. 2023 Jan 2;323:198952. doi: 10.1016/j.virusres.2022.198952. Epub 2022 Oct 27. 
40.    Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med. 2020 Apr 14;18(1):164. doi: 10.1186/s12967-020-02339-3. PMID: 32290839; PMCID: PMC7154566.
41.    National Institutes of Health. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Available from: https://wayback.archive-it.org/4887/20240626155208/https://www.covid19treatmentguidelines.nih.gov/ (Accessed on October 25, 2023).
42.    Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Available from: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/ (Accessed on February 21, 2021).
43.    Flowchart of diagnosis and treatment of covid-19 disease at outpatient and inpatient levels. 7th version, June 27, 2020. Available from:. chrome-extension://kdpelmjpfafjppnhbloffcjpeomlnpah/https://treatment.sbmu.ac.ir/uploads/oldfile/7__dastoor_flochart_treatment_covid_19.pdf. (Accessed on September 18, 2024).
Trends in Pharmaceutical Sciences
Volume 11, Issue 1
March 2025
Pages 1-16

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