Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. May 26, 2023; 15(5): 273-283
Published online May 26, 2023. doi: 10.4330/wjc.v15.i5.273
Impact of erythropoietin therapy on cardiorenal syndrome: A systematic review with meta-analysis
Rubal Bhangal, Ivan Cancarevic, Mahmoud Nassar, Zaryab Umar
Rubal Bhangal, Ivan Cancarevic, Zaryab Umar, Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals Queens, New York, NY 11432, United States
Mahmoud Nassar, Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Mahmoud Nassar, Department of Internal Medicine, NYC Health+Hospital Queens, New York, NY 11432, United States
Author contributions: All author contributed equally; All authors have read and approved the final version.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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:
Corresponding author: Mahmoud Nassar, MD, MSc, PhD, Doctor, Department of Internal Medicine, NYC Health+Hospital Queens, New York, NY 11432, United States.
Received: December 19, 2022
Peer-review started: December 19, 2022
First decision: February 8, 2023
Revised: March 24, 2023
Accepted: April 4, 2023
Article in press: April 4, 2023
Published online: May 26, 2023
Research background

Cardiorenal syndrome (CRS) describes a pathophysiological disorder of the heart and kidneys, whereby dysfunction of one system may contribute to dysfunction of another. Many patients with heart failure also experience kidney dysfunction and vice versa, as these two organs are closely related in their functions. Poor renal plasma flow in congestive heart failure (CHF) causes the kidneys to retain water and sodium, which allows for improved perfusion of all essential organs, leading to kidney dysfunction.

Research motivation

Anemia exacerbates CHF's progression and increases the risk of morbidity and mortality, and increasing hemoglobin (Hb) levels can limit the detrimental effects of oxidative stress on the kidney and cardiac function. Erythropoietin (EPO) treatment is an efficient approach to increase Hb levels in patients with CHF whose anemia is caused by reduced EPO production. Investigating the role of EPO in treating patients with CRS is of great significance as it could significantly decrease the mortality and hospitalization of CRS patients and lead to lower healthcare costs.

Research objectives

This systematic review evaluated the use of erythropoietin (EPO) in patients with CRS and its effects on Hb, major cardiovascular (CV) events, and hospitalization rates. The study aimed to deepen our understanding of the role of EPO in managing CRS and whether it can be a promising treatment option for many patients. The primary objective was to assess the efficacy of EPO therapy in improving cardiac and renal function in CRS patients.

Research methods

The article was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search was conducted on PubMed, MEDLINE, and EMBASE databases using a search strategy consisting of medical subject headings terms and regular keywords. Two reviewers independently examined titles and abstracts, followed by a second screening of full-length articles. Quality assessment was performed using the 2013 National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools for controlled intervention studies and observational cohort or cross-sectional studies. A meta-analysis was performed using Review Manager 5.4.1 software, and meta-analysis studies with forest plots were included for the outcomes. In vitro studies, animal studies, abstracts, case reports, case series, systematic reviews, and meta-analyses were excluded. Furthermore, articles in languages other than English were excluded.

Research results

This study selected 148 relevant articles and narrowed them down to nine studies that were evaluated using the NHLBI quality assessment tools. The majority of the studies concluded that EPO therapy increased Hb levels in patients with CRS and reduced anemia symptoms such as fatigue, malaise, weakness, and dizziness. However, the degree of Hb improvement varied significantly between the studies and was highly dependent on the dose and frequency of EPO administration. The effect of EPO on CV mortality is difficult to establish as different studies have reported varying outcomes. EPO use was associated with an increased risk of hospitalization, major CV events, acute coronary syndrome, and mortality in some studies. However, other studies found potential benefits of EPO on myocardial function and quality of life. The study's strength lies in its focus on randomized controlled clinical trials and cohort studies, while its limitations include publication bias and small sample sizes.

Research conclusions

The literature review provides evidence supporting the use of EPO therapy as a potential treatment option for patients with CRS. The benefits of EPO treatment in improving Hb levels, reducing major CV events, and improving cardiac remodeling, myocardial function, NYHA class, and BNP levels are significant, indicating a positive impact on the heart failure aspect of CRS and lowering the likelihood of death for patients. However, further studies are needed to investigate the effect of EPO treatment on hospitalization rates and potential side effects. Overall, the findings of this review suggest that EPO therapy may be a promising adjunctive treatment option for CRS, and more research is needed to confirm its effectiveness and optimize its use in clinical practice.

Research perspectives

In terms of future research perspectives, it is crucial to investigate the potential long-term effects of EPO therapy in patients with CRS. Since CRS is a chronic condition, examining the long-term effects of EPO treatment will provide valuable insights into its efficacy and safety. Additionally, future studies should explore the potential of combining EPO therapy with other treatments for CRS, such as angiotensin-converting enzyme inhibitors and beta blockers, to determine if combination therapy could improve clinical outcomes. Finally, future research should also aim to identify biomarkers that can predict a patient's response to EPO therapy, which would allow for more personalized treatment approaches.