Association of Anti-EPOR Antibodies with Clinicopathological Findings in Patients with IgA Nephropathy

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Background: Disease severity in immunoglobulin A nephropathy (IgAN) is mainly determined by pathological findings. Noninvasive and more convenient biomarkers are thus required for evaluating its activity. In previous studies, the presence of autoantibodies to the erythropoietin receptor (anti-EPOR antibodies) has been shown to be associated with high disease activity and kidney function decline in patients with various kidney diseases including lupus nephritis, type 2 diabetes, and anti-neutrophil cytoplasmic antibody-associated vasculitis. In this study, we therefore investigated the association of anti-EPOR antibodies with clinical and pathological findings in patients with IgAN. Methods: This retrospective cohort study included 56 patients with biopsy-proven IgAN between 2006 and 2016 at Kanazawa University Hospital. Serum anti-EPOR antibodies at kidney biopsy were measured by using enzyme-linked immunosorbent assays. We then evaluated the associations of anti-EPOR antibodies with clinical and pathological characteristics. Results: The presence of anti-EPOR antibodies was detected in 12 (21%) patients. Mean age, eGFR, and hemoglobin were comparable at baseline between the patients with and without anti-EPOR antibodies. Serum IgA/C3 ratio was higher in patients with anti-EPOR antibodies than those without (4.33 versus 3.19, p = 0.001). For pathological findings, patients with anti-EPOR antibodies were more likely to have active glomerular lesions, such as crescents or adhesions, compared to those without (91.7% versus 66.7%). During mean follow-up of 7.6 years, no statistical differences were found in annual eGFR declines between the patients with and without anti-EPOR antibodies (Mean±SD: 1.4±3.8 vs. 3.0±3.8 ml/min/1.73 m2/year). Conclusions: The presence of anti-EPOR antibodies may reflect disease activity in patients with IgAN. Funding: Government Support - Non-U.S.

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