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

• Published in: Kidney international reports Vol. 6; no. 2; pp. 284 - 295
• Main Authors: Oshima, Megumi, Hara, Akinori, Toyama, Tadashi, Jun, Min, Pollock, Carol, Jardine, Meg, Harrap, Stephen, Poulter, Neil, Cooper, Mark E., Woodward, Mark, Chalmers, John, Perkovic, Vlado, Wong, Muh Geot, Wada, Takashi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2021; Elsevier
• Subjects: biomarker; Clinical Research; end-stage kidney disease; type 2 diabetes; biomarker; end-stage kidney disease; type 2 diabetes
• ISSN: 2468-0249; 2468-0249
• DOI: 10.1016/j.ekir.2020.10.039

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. 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. 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. 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. [Display omitted]