Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor

Megumi Oshima; Akinori Hara; Tadashi Toyama; Min Jun; Carol Pollock; Meg Jardine; Stephen Harrap; Neil Poulter; Mark E. Cooper; Mark Woodward; John Chalmers; Vlado Perkovic; Muh Geot Wong; Takashi Wada

Kidney International Reports (Feb 2021)

Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor

Megumi Oshima,
Akinori Hara,
Tadashi Toyama,
Min Jun,
Carol Pollock,
Meg Jardine,
Stephen Harrap,
Neil Poulter,
Mark E. Cooper,
Mark Woodward,
John Chalmers,
Vlado Perkovic,
Muh Geot Wong,
Takashi Wada

Affiliations

Megumi Oshima: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan; Renal Department, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales, Australia
Akinori Hara: Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
Tadashi Toyama: Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
Min Jun: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
Carol Pollock: Renal Department, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales, Australia
Meg Jardine: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; Nephrology Unit, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
Stephen Harrap: Department of Physiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
Neil Poulter: International Center for Circulatory Health, Imperial College, London, UK
Mark E. Cooper: Departiment of Diabetes, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
Mark Woodward: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; The George Institute for Global Health, University of Oxford, Oxford, UK; Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
John Chalmers: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
Vlado Perkovic: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
Muh Geot Wong: Department of Renal and Metabolic, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; Renal Department, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales, Australia; Muh Geot Wong, Level 5, 1 King St, Newtown, Sydney, New South Wales, Australia 2042.
Takashi Wada: Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan; Correspondence: Takashi Wada, 13-1 Takara-machi, Kanazawa, Ishikawa, Japan 920-8641.

Journal volume & issue: Vol. 6, no. 2
pp. 284 – 295

Abstract

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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. Methods: In this nested case-control study from the ADVANCE trial cohort, we included 165 case participants who had the composite kidney outcome (renal replacement therapy, renal death, or doubling of serum creatinine to ≥200 μmol/l) and 330 matched controls. We compared the associations of baseline plasma levels of anti-EPOR antibodies, tumor necrosis factor receptor (TNFR)-1 and -2, and bone morphogenetic protein (BMP)-7 with kidney outcomes. Results: Cases had higher baseline plasma levels of anti-EPOR antibodies than controls (median 1.7 vs. 0.6 enzyme-linked immunosorbent assay unit, P < 0.001). Higher levels of anti-EPOR antibodies were associated with an increased risk of kidney outcome (odds ratio 2.16 [95% confidence interval 1.51, 3.08], per 1 SD of log-transformed levels) after adjusting for conventional markers. Elevated circulating TNFR1 and TNFR2 levels, and lower BMP-7 levels at baseline, were associated with poor kidney outcome (odds ratios 2.06 [1.29, 3.30], 1.66 [1.13, 2.43], and 0.45 [0.32, 0.65], respectively). The addition of anti-EPOR antibodies into the model improved the prediction of kidney outcome, regardless of other biomarkers. Conclusion: Anti-EPOR antibodies provide a promising biomarker, as with TNFR1, TNFR2, and BMP-7, in predicting kidney disease progression in people with type 2 diabetes mellitus.

Published in Kidney International Reports

ISSN: 2468-0249 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the genitourinary system. Urology
Website: http://www.journals.elsevier.com/kidney-international-reports/

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