Associations between kidney injury markers and COVID-19 severity: A retrospective study from a tertiary hospital

Salma AlBahrani; Thekra N Al-Maqati; Lamiaa Hamad Al-Jamea; Faisal Salem  Al Khalaf; Rawan M  Maawadh; Wael  Nazzal; Rania Saad  Suliman; Abrar Ahmed  Allahow; Rashid Ali  Al Asmari; Mansour Yeanallah Alghamdi; Sultan Ali  Alshehri; Abdullah Ali  AlQarni; Dana Khalid  ALSubaie; Taghreed Abdullah  Awadh; Hassan Mohammad  Talie; Elmoeiz A.  Elnagi

doi:10.23750/abm.v96i6.17445

Associations between kidney injury markers and COVID-19 severity: A retrospective study from a tertiary hospital

Authors

Salma AlBahrani Internal Medicine Department, King Fahad Military Medical Complex, and Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dhahran, Saudi Arabia
Thekra N Al-Maqati Department of Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia https://orcid.org/0000-0001-5705-2053
Lamiaa Hamad Al-Jamea Academic Affairs and Training Department, King Fahad Military Medical Complex, Ministry of Defense Health Services, Dhahran, Saudi Arabia
Faisal Salem Al Khalaf Department of Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
Rawan M Maawadh Department of Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences, Dammam,Saudi Arabia
Wael Nazzal Department of Obstetrics and Gynecology, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Rania Saad Suliman Department of Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
Abrar Ahmed Allahow Patient Services Administration Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Rashid Ali Al Asmari Nursing Administration Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Mansour Yeanallah Alghamdi Preventive Medicine Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Sultan Ali Alshehri Nursing Administration Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Abdullah Ali AlQarni Department of Medical Laboratory, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Dana Khalid ALSubaie Administration of laboratories and blood bank, security forces hospital program, Dammam, Saudi Arabia
Taghreed Abdullah Awadh Department of Medical Laboratory, King Fahad Military Medical Complex, Dhahran, Saudi Arabia
Hassan Mohammad Talie Patient Affairs Department, Armed Forces Hospitals Southern Region, Khamis Mushayt, Saudi Arabia
Elmoeiz A. Elnagi Department of Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia

Keywords:

kidney injury, COVID-19, kidney biomarkers, COVID-19 severity

Abstract

Background and aim: COVID-19 pandemic has been linked with many organ complications, among them being acute kidney injury (AKI), which is related to worse clinical outcomes. Understanding the relationship between renal biomarkers and disease severity is important in providing early detection and better management of high-risk patients. The current study explores the correlation between biomarkers of kidney injury and COVID-19 severity in hospitalized patients at a Saudi Arabian tertiary care hospital. Methods: A retrospective, single-centre, study was conducted on 450 adult patients who were hospitalized with laboratory-confirmed COVID-19 between March 2020 and December 2021. Demographics, comorbidities, clinical outcomes, and renal biomarkers including serum creatinine, blood urea nitrogen (BUN), sodium, potassium, chloride, and CO₂ were assessed. Statistical testing and multinomial logistic regression were used to assess the association of biomarker levels with disease severity (mild, severe, critical). Results: Elevated BUN was strongly associated with critical group (46.7%) compared to severe (23.6%) and mild (22.8%) cases (p < 0.001). Abnormal potassium, chloride, and CO₂ levels were also strongly associated with severity. The creatinine and sodium levels, however, were not significantly associated. Logistic regression validated BUN as an independent predictor of severity (OR for critical = 1.125, p < 0.001), whereas potassium and chloride demonstrated reverse relationships with severity levels. There was weak reverse correlation of creatinine. Conclusion: BUN, potassium, and chloride may serve as useful indicators of COVID-19 severity and could be useful biomarkers for the early risk stratification. Compliance with these parameters may facilitate early intervention and improve clinical outcomes in COVID-19 patients with AKI.

References

1. Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97(5):829-38. doi: 10.1016/j.kint.2020.03.005.

2. Stirparo G, Fagoni N, Bellini L, et al. Cardiopulmonary resuscitation missed by bystanders: Collateral damage of coronavirus disease 2019. Acta Anaesthesiol Scand. 2022;66(9):1124-9. doi: 10.1111/aas.14117.

3. Nadim MK, Forni LG, Mehta RL, et al. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol. 2020;16(12):747-64. doi: 10.1038/s41581-020-00356-5.

4. Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med. 2020;8(7):738-42. doi: 10.1016/S2213-2600(20)30229-0.

5. Guan W-j, Ni Z-y, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020;382(18):1708-20. doi: 10.1056/NEJMoa2002032

6. Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98(1):209-18. doi: 10.1016/j.kint.2020.05.006.

7. Fanelli V, Fiorentino M, Cantaluppi V, et al. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care. 2020;24(1):155. doi: 10.1186/s13054-020-02872-z.

8. Gabarre P, Dumas G, Dupont T, Darmon M, Azoulay E, Zafrani L. Acute kidney injury in critically ill patients with COVID-19. Intensive Care Med. 2020;46(7):1339-48. doi: 10.1007/s00134-020-06153-9.

9. Chan L, Chaudhary K, Saha A, et al. AKI in Hospitalized Patients with COVID-19. J Am Soc Nephrol. 2021;32(1):151-60. doi: 10.1681/ASN.2020050615.

10. Grams ME, Sang Y, Coresh J, et al. Acute Kidney Injury After Major Surgery: A Retrospective Analysis of Veterans Health Administration Data. Am J Kidney Dis. 2016;67(6):872-80. doi: 10.1053/j.ajkd.2015.07.022.

11. Ronco C, Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol. 2020;16(6):308-10. doi: 10.1038/s41581-020-0284-7.

12. Chen D, Li X, Song Q, et al. Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19). medRxiv. 2020:2020.02.27.20028530. doi: https://doi.org/10.1101/2020.02.27.20028530

13. Funk GC, Lindner G, Druml W, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010;36(2):304-11. doi: 10.1007/s00134-009-1692-0.

14. Kim HJ. Metabolic Acidosis in Chronic Kidney Disease: Pathogenesis, Clinical Consequences, and Treatment. Electrolyte Blood Press. 2021;19(2):29-37. doi: 10.5049/EBP.2021.19.2.29.

15. Shao M, Li X, Liu F, Tian T, Luo J, Yang Y. Acute kidney injury is associated with severe infection and fatality in patients with COVID-19: A systematic review and meta-analysis of 40 studies and 24,527 patients. Pharmacol Res. 2020;161:105107. doi: 10.1016/j.phrs.2020.105107.

16. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5.

17. Kudose S, Batal I, Santoriello D, et al. Kidney Biopsy Findings in Patients with COVID-19. J Am Soc Nephrol. 2020;31(9):1959-68. doi: 10.1681/ASN.2020060802.

18. Bakakos A, Koukaki E, Ampelioti S, et al. The Real Impact of Age on Mortality in Critically Ill COVID-19 Patients. J Pers Med. 2023;13(6). doi: 10.3390/jpm13060908

19. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. doi: 10.1136/bmj.m1295.

20. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20):2052-9. doi: 10.1001/jama.2020.6775.

21. Popkin BM, Du S, Green WD, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obes Rev. 2020;21(11):e13128. doi: 10.1111/obr.13128.

22. Kass DA, Duggal P, Cingolani O. Obesity could shift severe COVID-19 disease to younger ages. Lancet. 2020;395(10236):1544-5. doi: 10.1016/S0140-6736(20)31024-2.

23. Peckham H, de Gruijter NM, Raine C, et al. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun. 2020;11(1):6317. doi: 10.1038/s41467-020-19741-6.

24. Jin JM, Bai P, He W, et al. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health. 2020;8:152. doi: 10.3389/fpubh.2020.00152.

25. Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-6. doi: 10.1038/s41586-020-2521-4.

26. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395-403. doi: 10.1016/j.dsx.2020.04.018.

27. Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020;8(6):546-50. doi: 10.1016/S2213-8587(20)30152-2.

28. Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. doi: 10.1001/jamacardio.2020.1017.

29. Alqahtani JS, Oyelade T, Aldhahir AM, et al. Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. PLoS One. 2020;15(5):e0233147. doi: 10.1371/journal.pone.0233147.

30. Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. Jama. 2020;323(16):1574-81. doi: 10.1001/jama.2020.5394.

31. Armstrong RA, Kane AD, Cook TM. Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies. Anaesthesia. 2020;75(10):1340-9. doi: 10.1111/anae.15201.

32. Pei G, Zhang Z, Peng J, et al. Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. J Am Soc Nephrol. 2020;31(6):1157-65. doi: 10.1681/ASN.2020030276.

33. Borrego-Moreno JC, Cárdenas-de Luna MJ, Márquez-Castillo JC, et al. Acute Kidney Injury in the Context of COVID-19: An Analysis in Hospitalized Mexican Patients. Infect Dis Rep. 2024;16(3):458-71. doi: 10.3390/idr16030034.

34. Yin J, Wang Y, Jiang H, et al. Blood urea nitrogen and clinical prognosis in patients with COVID-19: A retrospective study. Medicine (Baltimore). 2024;103(8):e37299. doi: 10.1097/MD.0000000000037299

35. Zheng Z, Peng F, Xu B, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020;81(2):e16-e25. doi: 10.1016/j.jinf.2020.04.021.

36. Russo A, Pisaturo M, Monari C, et al. Prognostic Value of Creatinine Levels at Admission on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study. Pathogens. 2023;12(8). doi: 10.3390/pathogens12080973.

37. Li Q, Lin M, Deng Y, Huang H. The causal relationship between COVID-19 and estimated glomerular filtration rate: a bidirectional Mendelian randomization study. BMC Nephrology. 2024;25(1):21. doi: 10.1186/s12882-023-03443-4.

38. Zhong X, Wang X, Feng X, Yu H, Chen Z, Chen X. The blood urea nitrogen-to-creatinine ratio is associated with acute kidney injury among COVID-19 patients. Ren Fail. 2025;47(1):2442049. doi: 10.1080/0886022X.2024.2442049.

39. Alfano G, Fontana F, Mori G, et al. Acid base disorders in patients with COVID-19. Int Urol Nephrol. 2022;54(2):405-10. doi: 10.1007/s11255-021-02855-1.

40. Lippi G, South AM, Henry BM. Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19). Ann Clin Biochem. 2020;57(3):262-5. doi: 10.1177/0004563220922255.

41. Nogueira GM, Silva N, Moura AF, Duarte Silveira MA, Moura-Neto JA. Acute kidney injury and electrolyte disorders in COVID-19. World J Virol. 2022;11(5):283-92. doi: 10.5501/wjv.v11.i5.283.

42. Kim Y, Kwon S, Kim SG, et al. Impact of decreased levels of total CO2 on in-hospital mortality in patients with COVID-19. Scientific Reports. 2023;13(1):16717.doi: https://doi.org/10.1038/s41598-023-41988-4

43. Ciortea D-A, Petrea CL, Berbece SI, et al. Impact of Hyponatremia and ADH Secretion in MIS-C and COVID-19: An Integrative Approach of Prognostic and Diagnostic Markers. Current Issues in Molecular Biology [Internet]. 2024; 46(11):[11749-71 pp.]. doi: 10.3390/cimb46110698.

44. Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney Int. 2020;97(5):824-8. doi: 10.1016/j.kint.2020.03.001.

45. Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98(1):219-27. doi: 10.1016/j.kint.2020.04.003.