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World J Nephrol. Sep 25, 2025; 14(3): 107582
Published online Sep 25, 2025. doi: 10.5527/wjn.v14.i3.107582
Kidney involvement and anemia in COVID-19 infection
Guido Gembillo, Luigi Peritore, Giuseppe Spadaro, Felicia Cuzzola, Michela Calderone, Rossella Messina, Simona Di Piazza, Flavia Sudano, Maria Elsa Gambuzza, Maria Princiotto, Luca Soraci, Domenico Santoro
Guido Gembillo, Luigi Peritore, Giuseppe Spadaro, Felicia Cuzzola, Michela Calderone, Rossella Messina, Simona Di Piazza, Flavia Sudano, Domenico Santoro, Unit of Nephrology and Dialysis, AOU "G. Martino", University of Messina, Messina 98125, Sicilia, Italy
Maria Elsa Gambuzza, Territorial Office of Messina, Ministry of Health, Messina 98125, Sicilia, Italy
Maria Princiotto, Luca Soraci, Unit of Geriatric Medicine, Italian National Research Center on Aging (IRCCS INRCA), Cosenza 87100, Calabria, Italy
Co-corresponding authors: Guido Gembillo and Luca Soraci.
Author contributions: Gembillo G, Peritore L, Santoro D, and Soraci L contributed to the literature search; Gembillo G, Santoro D, Spadaro G, and Cuzzola F contributed to conceptualization; Calderone M, Messina R, Di Piazza S, Gambuzza ME, and Princiotto M contributed to study selection; Gembillo G, Peritore L, Soraci L, and Sudano F contributed to manuscript drafting; both Gembillo G and Soraci L played indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors; all authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: We have no conflict of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guido Gembillo, Unit of Nephrology and Dialysis, AOU "G. Martino", University of Messina, Via Consolare Valeria n 1, Messina 98125, Sicilia, Italy. ggembillo@gmail.com
Received: March 26, 2025
Revised: May 7, 2025
Accepted: July 24, 2025
Published online: September 25, 2025
Processing time: 175 Days and 10.5 Hours
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), has infected > 700 million people and led to > 7 million deaths worldwide. Although COVID-19 primarily affects the lungs, it can also affect the kidneys through various pathways. SARS-CoV-2 affects the kidney via several common mechanisms, such as dysregulation of angiotensin-converting enzyme 2, transmembrane serine protease 2 and tissue proteinase L expression in kidney tissue. People with chronic kidney disease (CKD) and COVID-19 have an increased risk of mortality and hospitalization in the intensive care unit. Anemia, a common consequence of CKD, is also associated with worsening outcomes in COVID-19 patients. In these patients with multiple comorbidities, there is a sharp increase in D-dimers, inflammatory parameters, creatinine and blood urea nitrogen. COVID-19 patients also present with resistance to erythropoietin (EPO)-stimulating agents, which necessitates elevated dosages even several months post-infection. In CKD, anemia is exacerbated by decreased EPO production, red blood cell (RBC) fragmentation due to impairment of the renovascular endothelium in situations such as glomerulopathy and malignant hypertension. Other factors include iron and/or folic acid deficiency, bleeding due to platelet dysfunction, inflammation, reduced RBC lifespan, poor iron utilization, uremia, and atypical blood loss after dialysis. Excessive hepcidin synthesis impairs the absorption of dietary iron and the mobilization of iron from endogenous reserves, thus contributing significantly to anemia and poor iron regulation in CKD. These findings suggest that CKD may contribute to the occurrence of anemia in COVID-19 patients, especially in older people with comorbidities. Our review aims to explore the complex relationship between CKD, COVID-19 and anemia to improve our understanding of the underlying mechanisms of the disease and the potential cofactors that worsen outcomes in these patients.

Keywords: COVID 19; Hemodialysis; Renal transplant; Erythropoietin; Peritoneal dialysis; Iron deficiency; Renal anemia; Systemic inflammation; Renal replacement therapy

Core Tip: Severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease 2019 (COVID-19) infection, has had a major impact worldwide. People with chronic kidney disease (CKD) and COVID-19 have an increased risk of mortality and hospitalization, with anemia, which is common in CKD, exacerbating outcomes. Patients with CKD show resistance to erythropoietin (EPO)-stimulating agents and require higher doses even after infection. Anemia in CKD is exacerbated by factors such as decreased EPO production, red blood cell fragmentation, iron or folic acid deficiency, platelet dysfunction and excessive hepcidin synthesis. These factors contribute to poor iron regulation, which further complicates anemia in COVID-19 patients.