Dataset Information

Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial.

ABSTRACT:

Introduction

Autoantibodies to erythropoietin receptor (anti-EPOR antibodies) have been identified in patients with various kidney diseases. However, data in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) is limited. We assessed the prevalence of anti-EPOR antibodies and their association with clinical outcomes in this population.

Methods

The CREDENCE randomized patients with T2D and CKD to canagliflozin or placebo. Serum anti-EPOR antibodies, the exposure of interest, were measured using enzyme-linked immunosorbent assay. The primary outcome was doubling of serum creatinine, end-stage kidney disease, or death from kidney or cardiovascular (CV) causes. Secondary outcomes included CV and all-cause mortality. Multivariable Cox-regression models estimated associations between anti-EPOR antibodies and outcomes. The effects of canagliflozin on hemoglobin and hematocrit, stratified by the presence of anti-EPOR antibodies were assessed with a repeated measures mixed effects model.

Results

Of 2600 participants with available biosamples, 191 (7.3%) were positive for anti-EPOR antibodies. Higher baseline anti-EPOR antibodies were associated with increased risk of primary outcome (hazard ratio [HR] per 1-SD increase = 1.12, 95% confidence interval [CI] = 1.01-1.24, P = 0.04), with CV death (HR = 1.27, 95% CI = 1.08-1.48, P < 0.01) and all-cause mortality (HR = 1.26, 95% CI = 1.11-1.43, P < 0.01). During follow-up, canagliflozin, compared to placebo, increased hemoglobin and hematocrit by 7.0 g/l (95% CI = 6.2-7.9) and 2.4% (2.2-2.7), respectively. These effects were consistent across patients with and without anti-EPOR antibodies (P-interaction = 0.24 and 0.36, respectively).

Conclusion

In patients with T2D and CKD, anti-EPOR antibodies were associated with the composite kidney and CV outcome, as well as CV and all-cause mortality. Canagliflozin increased hemoglobin and hematocrit regardless of anti-EPOR antibodies.

SUBMITTER: Koshino A

PROVIDER: S-EPMC10850998 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A <i>Post Hoc</i> Analysis of CREDENCE Trial.

Koshino Akihiko A Neuen Brendon L BL Oshima Megumi M Toyama Tadashi T Hara Akinori A Arnott Clare C Neal Bruce B Jardine Meg M Badve Sunil V SV Mahaffey Kenneth W KW Pollock Carol C Hansen Michael K MK Wada Takashi T Heerspink Hiddo J L HJL

Kidney international reports 20231201 2

<h4>Introduction</h4>Autoantibodies to erythropoietin receptor (anti-EPOR antibodies) have been identified in patients with various kidney diseases. However, data in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) is limited. We assessed the prevalence of anti-EPOR antibodies and their association with clinical outcomes in this population.<h4>Methods</h4>The CREDENCE randomized patients with T2D and CKD to canagliflozin or placebo. Serum anti-EPOR antibodies, the exposure of ...[more]

PMID: 38344715

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