TY - JOUR
T1 - Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor
AU - Oshima, Megumi
AU - Hara, Akinori
AU - Toyama, Tadashi
AU - Jun, Min
AU - Pollock, Carol
AU - Jardine, Meg
AU - Harrap, Stephen
AU - Poulter, Neil
AU - Cooper, Mark E.
AU - Woodward, Mark
AU - Chalmers, John
AU - Perkovic, Vlado
AU - Wong, Muh Geot
AU - Wada, Takashi
N1 - Funding Information:
MO and TT are supported by the Japan Society for the Promotion of Science Program for Fostering Globally Talented Researchers. M Jun is supported by a Scientia Fellowship from the University of New South Wales Sydney and reports receiving research support from the Australian National Health and Medical Research Council and VentureWise (a wholly owned subsidiary of NPS MedicineWise) to conduct a project funded by AstraZeneca. CP has received honoraria for serving on advisory boards and as a speaker for Merck Sharpe. M Jardine is supported by a Medical Research Future Fund Next Generation Clinical Researchers Program Career Development Fellowship; is responsible for research projects that have received unrestricted funding from Baxter, Amgen, Eli Lilly, and Merck Sharpe Dohme; serves on a Steering Committee sponsored by CSL; has served on advisory boards sponsored by Akebia, Baxter, Boehringer Ingelheim, and Vifor; and has spoken at scientific meetings sponsored by Janssen; with any consultancy, honoraria, or travel support paid to her institution. SH reports lecture fees from Servier, Takeda, and Novartis. NP received honoraria from Servier Laboratories, Takeda Pharmaceutical Company, Menarini Group, and Pfizer, grant support from Servier Laboratories, and Pfizer and personal fees from Servier Laboratories, Takeda Pharmaceutical Company, Menarini Group, and Pfizer. MEC received consulting fees from Merck, GlaxoSmithKline, Amgen and AstraZeneca, and lecture fees from Servier. MW reports consultancy fees from Amgen and Kirin and is supported by National Health and Medical Research Foundation of Australia grants 1080206 and 1149987. JC received research grants from the National Health and Medical Research Council of Australia and from Servier for the ADVANCE trial and ADVANCE-ON post-trial follow-up, and honoraria for speaking about these studies at scientific meetings, and reports grant support from Program Grant APP1149987 from the National Health and Medical Research Council of Australia. VP has received fees for advisory boards, steering committee roles or scientific presentations from AbbVie, Astellas, AstraZeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, Vifor, and Tricida. MGW has received honorarium for scientific lectures from AstraZeneca, Amgen and Baxter, and is supported by a Diabetes Australia Research Trust Millennium Grant. TW received research grants from Shiseido Company and honoraria for speaking from Kirin and Mitsubishi Tanabe Pharma Corporation. AH declared no competing interests.
Funding Information:
The biomarker work was funded by the Japan Society for the Promotion of Science Program for Fostering Globally Talented Researchers, the George Institute for Global Health (Sydney, Australia), and the Diabetes Australia Millennium Grant. The ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) was funded by the grants from the National Health and Medical Research Council (NHMRC) of Australia and Servier. The funders were not involved in the study design, data collection, data analysis, data interpretation, writing this report, or the decision to submit the report for publication. All authors had full access to all the data and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2020 International Society of Nephrology
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - biomarker
KW - end-stage kidney disease
KW - type 2 diabetes
UR - https://www.scopus.com/pages/publications/85098879630
U2 - 10.1016/j.ekir.2020.10.039
DO - 10.1016/j.ekir.2020.10.039
M3 - Article
C2 - 33615053
AN - SCOPUS:85098879630
SN - 2468-0249
VL - 6
SP - 284
EP - 295
JO - Kidney International Reports
JF - Kidney International Reports
IS - 2
ER -
