Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial
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...
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Elsevier
2024-02-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024923016133 |
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| author | Akihiko Koshino Brendon L. Neuen Megumi Oshima Tadashi Toyama Akinori Hara Clare Arnott Bruce Neal Meg Jardine Sunil V. Badve Kenneth W. Mahaffey Carol Pollock Michael K. Hansen Takashi Wada Hiddo J.L. Heerspink |
| author_facet | Akihiko Koshino Brendon L. Neuen Megumi Oshima Tadashi Toyama Akinori Hara Clare Arnott Bruce Neal Meg Jardine Sunil V. Badve Kenneth W. Mahaffey Carol Pollock Michael K. Hansen Takashi Wada Hiddo J.L. Heerspink |
| author_sort | Akihiko Koshino |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4bbeffd5bfad4b1d8618533bd597bd4b |
| institution | OA Journals |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-4bbeffd5bfad4b1d8618533bd597bd4b2025-08-20T02:31:47ZengElsevierKidney International Reports2468-02492024-02-019234735510.1016/j.ekir.2023.11.024Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE TrialAkihiko Koshino0Brendon L. Neuen1Megumi Oshima2Tadashi Toyama3Akinori Hara4Clare Arnott5Bruce Neal6Meg Jardine7Sunil V. Badve8Kenneth W. Mahaffey9Carol Pollock10Michael K. Hansen11Takashi Wada12Hiddo J.L. Heerspink13Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, JapanThe George Institute for Global Health, University of New South Wales Sydney, Sydney, New South Wales, AustraliaDepartment of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, JapanDepartment of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, JapanDepartment of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, JapanThe George Institute for Global Health, University of New South Wales Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, AustraliaThe George Institute for Global Health, University of New South Wales Sydney, Sydney, New South Wales, Australia; School of Public Health, Imperial College London, UKThe George Institute for Global Health, University of New South Wales Sydney, Sydney, New South Wales, Australia; NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia; Concord Repatriation General Hospital, Sydney, New South Wales, AustraliaThe George Institute for Global Health, University of New South Wales Sydney, Sydney, New South Wales, Australia; Department of Nephrology, St George Hospital, Sydney, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, AustraliaStanford Center for Clinical Research, Stanford University School of Medicine, Stanford, California, USAKolling Institute of Medical Research, Sydney Medical School, University of Sydney, New South Wales, Australia; Royal North Shore Hospital, St Leonards, New South Wales, AustraliaJanssen Research and Development, LLC, Spring House, Pennsylvania, USADepartment of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan; Correspondence: Takashi Wada, Department of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-0934, Japan.Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; The George Institute for Global Health, University of New South Wales Sydney, Sydney, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, AustraliaIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2468024923016133anemiabiomarkercardiovascularkidneymortalitySGLT2 inhibitor |
| spellingShingle | Akihiko Koshino Brendon L. Neuen Megumi Oshima Tadashi Toyama Akinori Hara Clare Arnott Bruce Neal Meg Jardine Sunil V. Badve Kenneth W. Mahaffey Carol Pollock Michael K. Hansen Takashi Wada Hiddo J.L. Heerspink Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial Kidney International Reports anemia biomarker cardiovascular kidney mortality SGLT2 inhibitor |
| title | Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial |
| title_full | Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial |
| title_fullStr | Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial |
| title_full_unstemmed | Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial |
| title_short | Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A Post Hoc Analysis of CREDENCE Trial |
| title_sort | autoantibodies to erythropoietin receptor and clinical outcomes in patients with type 2 diabetes and ckd a post hoc analysis of credence trial |
| topic | anemia biomarker cardiovascular kidney mortality SGLT2 inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S2468024923016133 |
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