#1881 Association of circulating autoantibodies to erythropoietin receptor with anaemia in patients with type 2 diabetes and chronic kidney disease

Abstract

Abstract Background and Aims Anaemia is a risk factor for cardiovascular and kidney prognosis in patients with type 2 diabetes and it is important to identify patients at high risk of anemia. We have previously reported that autoantibodies to erythropoietin receptor (anti-EPOR antibodies) may functionally neutralize the activity of erythropoietin and are associated with haemoglobin (Hb) in patients with lupus nephritis, and hypo responsiveness to erythropoiesis-stimulating agents (ESAs) in patients undergoing haemodialysis. This study assessed the association between anti-EPOR antibodies and anaemia in patients with type 2 diabetes and chronic kidney disease. Method This cohort study included patients with type 2 diabetes and chronic kidney disease who were diagnosed between 1989 and 2014 at our hospital. The presence of anti-EPOR antibodies at baseline were assessed by ELISA in stocked serum. To investigate the association between anti-EPOR antibodies and anaemia, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis adjusted for multiple covariates. We then estimated hazard ratios (HR) and 95% CIs using Cox regression models to investigate the association between anti-EPOR antibodies and the risk of iron deficiency, defined as transferrin saturation below 20% in those with follow-up measurements of iron metabolism. Results The mean age was 63 years, the mean eGFR was 42 ml/min/1.73 m2 and the median urinary protein to creatinine ratio (UPCR) was 1.8 g/gCr. Anti-EPOR antibodies were detected in 26 out of 110 patients (24%). At baseline, most patients with anti-EPOR antibodies had anaemia (n=24, 92%) and severe anaemia with Hb<10 g/dl (n=16, 62%) and used ESAs (n=16, 62%). The presence of anti-EPOR antibodies was independently associated with severe anaemia (OR 9.3; 1.2-70.1, p=0.03) after adjustment for baseline covariates including HbA1c, eGFR, UPCR, iron, and CRP. During a mean follow-up of 6.5 years, 6 of 10 patients (60%) developed iron deficiency in anti-EPOR antibodies positive patients, while 3 of 20 patients (15%) in negative patients. Patients with anti-EPOR antibodies were associated with an higher risk of iron deficiency compared to those without (HR 76.0; 95% CI 1.2-4721.7, p=0.04). Conclusion In patients with type 2 diabetes and chronic kidney disease, the presence of anti-EPOR antibodies was associated with a risk of severe anaemia and iron deficiency independently of kidney function. These results suggest that anti-EPOR antibodies may be useful in predicting the risk of anaemia and establishing therapeutic strategies of anaemia in people with type 2 diabetes.