Ferritin and mortality in hemodialysis patients with COVID-19: A systematic review and meta-analysis

Abstract

Objective: To investigate the difference in serum ferritin levels between deceased and surviving regular hemodialysis patients with COVID-19.

Methods: We conducted a systematic search across four databases following the PRISMA statement guidelines. Studies reporting ferritin levels and mortality of regular hemodialysis patients with COVID-19 were included. Employing the random-effects model, we performed a meta-analysis to determine the mean difference in serum ferritin levels between the studied groups, along with their corresponding 95% confidence intervals. The meta-analysis was carried out using Review Manager 5.4 and Stata 16.

Results: A total of 1 013 patients from seven studies were included in this study. Our meta-analysis showed higher mean serum ferritin in the deceased compared to surviving regular hemodialysis patients with COVID-19, with a mean difference of 449.43 ng/mL [95% CI (244.07, 654.80), P<0.000 1; I²=58%, P=0.003].

Conclusions: Our study found a higher mean of serum ferritin levels in the deceased compared to surviving regular hemodialysis patients with COVID-19.

Keywords

Ferritin / Mortality / Hemodialysis / COVID-19 / Inflammation

References

[1] Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. J Am Med Assoc 2020; 323(13): 1239-1242.

[2] World Health Organization. Living guidance for clinical management of COVID-19. Gevena: World Health Organization; 2021.

[3] Portolés J, Marques M, López-Sánchez P, de Valdenebro M, Muñez E, Serrano ML, et al. Chronic kidney disease and acute kidney injury in the COVID-19 Spanish outbreak. Nephrol Dial Transplant 2020; 35(8): 1353-1361.

[4] Askari H, Sanadgol N, Azarnezhad A, Tajbakhsh A, Rafiei H, Safarpour AR, et al. Kidney diseases and COVID-19 infection: Causes and effect, supportive therapeutics and nutritional perspectives. Heliyon 2021; 7(1): e06008.

[5] Ozturk S, Turgutalp K, Arid M, Odabas AR, Altiparmak MR, Aydin Z, et al. Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: A nationwide analysis from Turkey. Nephrol Dial Transplant 2020; 35(12): 2083-2095.

[6] Cheng L, Li H, Li L, Liu C, Yan S, Chen H, et al. Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J Clin Lab Anal 2020; 34(10): e23618.

[7] Rastad H, Ejtahed HS, Shafiee G, Safari A, Shahrestanaki E, Khodaparast Z, et al. The risk factors associated with COVID-19-related death among patients with end-stage renal disease. BMC Nephrol 2021; 22(1): 33.

[8] Edeas M, Saleh J, Peyssonnaux C. Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? Int J Infect Dis 2020; 97: 303-305.

[9] Sonnweber T, Boehm A, Sahanic S, Pizzini A, Aichner M, Sonnweber B, et al. Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients' performance: A prospective observational cohort study. Respir Res 2020; 21(1): 276.

[10] Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH. Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis 2001; 37(3): 564-572.

[11] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst Rev 2021; 10(1): 89.

[12] JROBINS-E Development Group. Risk of bias in non-randomized studies -of exposure (ROBINS-E). [Online]. Available from: https://www.riskofbias.info/welcome/robins-e-tool. [Accessed on 10 February 2023].

[13] Deek J, Higgins J, Altman D. Analysing data and undertaking meta-analyses. In: Cochrane handbook for systematic reviews of interventions. England: John Wiley & Sons Ltd; 2008, p. 244-296.

[14] Turgutalp K, Ozturk S, Arici M, Eren N, Gorgulu N, Islam M, et al. Determinants of mortality in a large group of hemodialysis patients hospitalized for COVID-19. BMC Nephrol 2021; 22(1): 29.

[15] Hakami A, Badedi M, Elsiddig M, Nadeem M, Altherwi N, Rayani R, et al. Clinical characteristics and early outcomes of hospitalized COVID-19 patients with end-stage kidney disease in Saudi Arabia. Int J Gen Med 2021; 14: 4837-4845.

[16] Hendra H, Vajgel G, Antonelou M, Neradova A, Manson B, Clark SG, et al. Identifying prognostic risk factors for poor outcome following COVID-19 disease among in-centre haemodialysis patients: Role of inflammation and frailty. J Nephrol 2021; 34(2): 315-323.

[17] Sipahi S, Dheir H, Toçoğlu A, Bektaş M, Açıkgöz SB, Genç AC, et al. Characteristics and mortality determinants of COVID-19 patients undergoing hemodialysis. Turkish J Med Sci 2021; 51(2): 421-427.

[18] Islam M, Ozturk Y, Koc Y. Clinical outcomes of COVID-19 in hemodialysis patients in the city of Zonguldak, Turkey. Int Urol Nephrol 2021; 53(7): 1445-1452.

[19] Fisher M, Yunes M, Mokrzycki MH, Golestaneh L, Alahiri E, Coco M. Chronic hemodialysis patients hospitalized with COVID-19: Short-term outcomes in the Bronx, New York. Kidney 360 2020; 1(8): 755-762.

[20] Donati G, Gasperoni L, Zappulo F, Scrivo A, Napoli M, Di Filippo F, et al. Interleukin-6 and outcome of chronic hemodialysis patients with SARS-CoV-2 pneumonia. Medicina (Kaunas) 2022; 58(11): 1659.

[21] Kim T, Streja E, Soohoo M, Rhee CM, Eriguchi R, Kim TW, et al. Serum ferritin variations and mortality in incident hemodialysis patients. Am J Nephrol 2017; 46(2): 120-130.

[22] Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol 2017; 29(9): 401-409.

[23] Kalantar-Zadeh K, Regidor DL, McAllister CJ, Michael B, Warnock DG. Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol 2005; 16(10): 3070-3080.

[24] Shoji T, Niihata K, Fukuma S, Fukuhara S, Akizawa T, Inaba M. Both low and high serum ferritin levels predict mortality risk in hemodialysis patients without inflammation. Clin Exp Nephrol 2017; 21(4): 685-693.

[25] de Lucena TMC, da Silva Santos AF, de Lima BR, de Albuquerque Borborema ME, de Azevêdo Silva J. Mechanism of inflammatory response in associated comorbidities in COVID-19. Diabetes Metab Syndr 2020; 14(4): 597-600.

[26] Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: An autopsy series from New Orleans. Lancet Respir Med 2020; 8(7): 681-686.

[27] Zayed RA, Omran D, Zayed AA. COVID-19 clinical and laboratory diagnosis overview. J Egypt Public Health Assoc 2021; 96(1): 25.

[28] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395(10229): 1033-1034.

[29] Kappert K, Jahi A, Tauber R. Assessment of serum ferritin as a biomarker in COVID-19: Bystander or participant? Insights by comparison with other infectious and non-infectious diseases. Biomarkers 2020; 25(8): 616-625.

[30] Pasini AMF, Stranieri C, Girelli D, Busti F, Cominacini L. Is ferroptosis a key component of the process leading to multiorgan damage in COVID-19? Antioxidants 2021; 10(11): 1677.

[31] Hippchen T, Altamura S, Muckenthaler MU, Merle U. Hypoferremia is associated with increased hospitalization and oxygen demand in COVID-19 patients. Hemasphere 2020; 4(6): e492.

[32] Bellmann-Weiler R, Lanser L, Barket R, Rangger L, Schapfl A, Schaber M, et al. Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection. J Clin Med 2020; 9(8): 2429.

[33] Chiou B, Connor JR. Emerging and dynamic biomedical uses of ferritin. Pharmaceuticals 2018; 11(4): 124.

[34] Carubbi F, Salvati L, Alunno A, Maggi F, Borghi E, Mariani R, et al. Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: Data from two Italian COVID-19 units. Sci Rep 2021; 11(1): 4863.

[35] Medjeral-Thomas NR, Thomson T, Ashby D, Muthusamy A, Nevin M, Duncan N, et al. Cohort study of outpatient hemodialysis management strategies for COVID-19 in North-West London. Kidney Int Rep 2020; 5(11): 2055-2065.

[36] Bataille S, Pedinielli N, Bergounioux JP. Could ferritin help the screening for COVID-19 in hemodialysis patients? Kidney Int 2020; 98(1): 235-236.

[37] Lino K, Guimarães GMC, Alves LS, Oliveira AC, Faustino R, Fernandes CS, et al. Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality. Brazilian J Infect Dis 2021; 25(2): 1-6.

[38] Sun Y, Chen P, Zhai B, Zhang M, Xiang Y, Fang J, et al. The emerging role of ferroptosis in inflammation. Biomed Pharmacother 2020; 127: 110108. doi: 10.1016/j.biopha.2020.110108.

[39] Yang M, Lai CL. SARS-CoV-2 infection: Can ferroptosis be a potential treatment target for multiple organ involvement? Cell Death Discov 2020; 6: 130. doi: 10.1038/s41420-020-00369-w.

[40] Park KS, Ryu GW, Jhee JH, Kim HW, Park S, Lee SA, et al. Serum ferritin predicts mortality regardless of inflammatory and nutritional status in patients starting dialysis: A prospective cohort study. Blood Purif 2015; 40(3): 209-217.

[41] Beck NS, Song S, Park T, Hong SH, Jeong-Eun J, Kim KH, et al. Clinical features of COVID-19 among patients with end-stage renal disease on hemodialysis in the context of high vaccination coverage during the omicron surge period: A retrospective cohort study. BMC Nephrol 2023; 24(1): 1-9.

[42] Melo AKG, Milby KM, Caparroz ALMA, Pinto ACPN, Santos RRP, Rocha AP, et al. Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis. PLoS One 2021; 16(6 June): 1-21.

[43] Murt A, Yadigar S, Yalin SF, Dincer MT, Parmaksiz E, Altiparmak MR. Arteriovenous fistula as the vascular access contributes to better survival of hemodialysis patients with COVID-19 infection. J Vasc Access 2023; 24(1): 22-26.

[44] Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med 2007; 26(25): 4544-4562.