Cardiac dysfunction is an important prognostic predictor of cardiovascular mortality in patients on hemodialysis (HD). Erythropoietin (EPO) has been reported to improve cardiac function by binding to the EPO receptor (EPOR) on cardiomyocytes. This study investigated whether anti-EPOR antibodies were associated with left ventricular cardiac function in patients undergoing HD. This multicenter, cross-sectional observational study included 377 patients (median age, 70 years; 267 (70.8%) males) with chronic kidney disease (CKD) undergoing stable maintenance HD. Serum levels of anti-EPOR antibodies were measured, and echocardiography was used to assess the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Anti-EPOR antibodies were found in 17 patients (4.5%). LVMI was greater (median of 135 g/m2 vs. 115 g/m2, p = 0.042), and the prevalence of LVEF < 50% was higher (35.3% vs. 15.6%, p = 0.032) in patients with anti-EPOR antibodies than in those without. Multivariable linear regression and logistic regression analysis (after adjusting for known risk factors of heart failure) revealed that anti-EPOR antibodies were independently associated with LVMI (coefficient 16.2%; 95% confidence interval (CI) 1.0−35.0%, p = 0.043) and LVEF <50% (odds ratio 3.20; 95% CI 1.05−9.73, p = 0.041). Thus, anti-EPOR antibody positivity was associated with left ventricular dysfunction in patients undergoing HD.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495431PMC
http://dx.doi.org/10.3390/biomedicines10092092DOI Listing

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Article Synopsis
  • Autoantibodies to erythropoietin receptor (anti-EPOR antibodies) have been found in some patients with kidney diseases, but their impact on those with type 2 diabetes (T2D) and chronic kidney disease (CKD) is not well understood.
  • In a study of 2,600 T2D and CKD patients, about 7.3% tested positive for these antibodies, which were linked to higher risks of serious kidney issues and cardiovascular deaths.
  • The diabetes medication canagliflozin was shown to effectively increase hemoglobin and hematocrit levels in all patients, regardless of their anti-EPOR antibody status.
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Association between Anti-Erythropoietin Receptor Antibodies and Cardiac Function in Patients on Hemodialysis: A Multicenter Cross-Sectional Study.

Biomedicines

August 2022

Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan.

Cardiac dysfunction is an important prognostic predictor of cardiovascular mortality in patients on hemodialysis (HD). Erythropoietin (EPO) has been reported to improve cardiac function by binding to the EPO receptor (EPOR) on cardiomyocytes. This study investigated whether anti-EPOR antibodies were associated with left ventricular cardiac function in patients undergoing HD.

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Introduction: Several circulating markers, including autoantibodies to erythropoietin receptor (anti-EPOR antibodies), have been identified as useful biomarkers in predicting diabetic kidney disease progression. However, a direct comparison of their utility is lacking. We aimed to validate and to compare the prognostic value of anti-EPOR antibodies with that of other known biomarkers, using the ADVANCE trial and its long-term follow-up, ADVANCE-ON, cohorts.

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Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival. To determine mechanisms by which a nonhematopoietic erythropoietin (EPO) derivative, carbamylated EPO (CEPO), regulates innate and adaptive immune cells and affects renal allograft survival, we utilized a rat model of fully MHC-mismatched kidney transplantation. CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group.

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Relationship between autoantibodies to erythropoietin receptor and renal outcome in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Biomarkers

March 2020

Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

We examined the relationship between autoantibodies to erythropoietin receptor (EPOR) and renal outcome in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Sixty-three Japanese patients with AAV were enrolled and followed for a median of 31.4 months.

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