Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia
Background: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also rela...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.634932/full |
| _version_ | 1818601574328434688 |
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| author | Tomohito Gohda Naotake Yanagisawa Maki Murakoshi Seiji Ueda Yuji Nishizaki Shuko Nojiri Yasuo Ohashi Iwao Ohno Yugo Shibagaki Naohiko Imai Satoshi Iimuro Masanari Kuwabara Hiroshi Hayakawa Kenjiro Kimura Tatsuo Hosoya Yusuke Suzuki |
| author_facet | Tomohito Gohda Naotake Yanagisawa Maki Murakoshi Seiji Ueda Yuji Nishizaki Shuko Nojiri Yasuo Ohashi Iwao Ohno Yugo Shibagaki Naohiko Imai Satoshi Iimuro Masanari Kuwabara Hiroshi Hayakawa Kenjiro Kimura Tatsuo Hosoya Yusuke Suzuki |
| author_sort | Tomohito Gohda |
| collection | DOAJ |
| description | Background: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also related with future GFR decline in patients with diabetes. The aims of this study are to investigate the association between baseline TNFR levels and early change in TNFR levels by the non-purine selective xanthine oxidase inhibitor, febuxostat, and future eGFR decline chiefly in chronic kidney disease (CKD) patients without diabetes.Methods: We conducted a post-hoc analysis of the FEATHER study on patients with asymptomatic hyperuricemia and CKD stage 3, who were randomly assigned febuxostat 40 mg/day or matched placebo. This analysis included 426 patients in whom baseline stored samples were available. Serum TNFR levels at baseline were measured using enzyme-linked immunosorbent assay. Those levels were also measured using 12-week stored samples from 197 randomly selected patients.Results: Compared with placebo, short-term febuxostat treatment significantly decreased the median percent change from baseline in serum uric acid (−45.05, 95% CI −48.90 to −41.24 mg/dL), TNFR1 (1.10, 95% CI−2.25 to 4.40), and TNFR2 (1.66, 95% CI −1.72 to 4.93), but not TNFR levels. Over a median follow-up of 105 weeks, 30 patients (7.0%) experienced 30% eGFR decline from baseline. In the Cox multivariate model, high levels of baseline TNFR predicted a 30% eGFR decline, even after adjusting for age, sex, systolic blood pressure, high sensitivity C-reactive protein, uric acid, and presence or absence of febuxostat treatment and diabetes, in addition to baseline albumin to creatinine ratio and eGFR.Conclusion: Early change in circulating TNFR levels failed to predict future eGFR decline; however, regardless of febuxostat treatment, the elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia. |
| first_indexed | 2024-12-16T12:53:33Z |
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| id | doaj.art-52beb291f3f449959e4629eecd215f07 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-16T12:53:33Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-52beb291f3f449959e4629eecd215f072022-12-21T22:31:04ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-07-01810.3389/fmed.2021.634932634932Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic HyperuricemiaTomohito Gohda0Naotake Yanagisawa1Maki Murakoshi2Seiji Ueda3Yuji Nishizaki4Shuko Nojiri5Yasuo Ohashi6Iwao Ohno7Yugo Shibagaki8Naohiko Imai9Satoshi Iimuro10Masanari Kuwabara11Hiroshi Hayakawa12Kenjiro Kimura13Tatsuo Hosoya14Yusuke Suzuki15Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, JapanMedical Technology Innovation Center, Juntendo University, Tokyo, JapanDepartment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, JapanDepartment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, JapanMedical Technology Innovation Center, Juntendo University, Tokyo, JapanMedical Technology Innovation Center, Juntendo University, Tokyo, JapanDepartment of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, JapanDivision of General Medicine, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanInnovation and Research Support Center, International University of Health and Welfare, Tokyo, JapanIntensive Care Unit, Department of Cardiology, Toranomon Hospital, Tokyo, JapanInternal Medicine, Kanto Central Hospital, Tokyo, JapanTokyo Takanawa Hospital, Tokyo, Japan0Division of Chronic Kidney Disease Therapeutics, The Jikei University, Tokyo, JapanDepartment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, JapanBackground: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also related with future GFR decline in patients with diabetes. The aims of this study are to investigate the association between baseline TNFR levels and early change in TNFR levels by the non-purine selective xanthine oxidase inhibitor, febuxostat, and future eGFR decline chiefly in chronic kidney disease (CKD) patients without diabetes.Methods: We conducted a post-hoc analysis of the FEATHER study on patients with asymptomatic hyperuricemia and CKD stage 3, who were randomly assigned febuxostat 40 mg/day or matched placebo. This analysis included 426 patients in whom baseline stored samples were available. Serum TNFR levels at baseline were measured using enzyme-linked immunosorbent assay. Those levels were also measured using 12-week stored samples from 197 randomly selected patients.Results: Compared with placebo, short-term febuxostat treatment significantly decreased the median percent change from baseline in serum uric acid (−45.05, 95% CI −48.90 to −41.24 mg/dL), TNFR1 (1.10, 95% CI−2.25 to 4.40), and TNFR2 (1.66, 95% CI −1.72 to 4.93), but not TNFR levels. Over a median follow-up of 105 weeks, 30 patients (7.0%) experienced 30% eGFR decline from baseline. In the Cox multivariate model, high levels of baseline TNFR predicted a 30% eGFR decline, even after adjusting for age, sex, systolic blood pressure, high sensitivity C-reactive protein, uric acid, and presence or absence of febuxostat treatment and diabetes, in addition to baseline albumin to creatinine ratio and eGFR.Conclusion: Early change in circulating TNFR levels failed to predict future eGFR decline; however, regardless of febuxostat treatment, the elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia.https://www.frontiersin.org/articles/10.3389/fmed.2021.634932/fullTNF receptorCKDuric acidxanthine oxidase inhibitoreGFR |
| spellingShingle | Tomohito Gohda Naotake Yanagisawa Maki Murakoshi Seiji Ueda Yuji Nishizaki Shuko Nojiri Yasuo Ohashi Iwao Ohno Yugo Shibagaki Naohiko Imai Satoshi Iimuro Masanari Kuwabara Hiroshi Hayakawa Kenjiro Kimura Tatsuo Hosoya Yusuke Suzuki Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia Frontiers in Medicine TNF receptor CKD uric acid xanthine oxidase inhibitor eGFR |
| title | Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia |
| title_full | Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia |
| title_fullStr | Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia |
| title_full_unstemmed | Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia |
| title_short | Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia |
| title_sort | association between kidney function decline and baseline tnfr levels or change ratio in tnfr by febuxostat chiefly in non diabetic ckd patients with asymptomatic hyperuricemia |
| topic | TNF receptor CKD uric acid xanthine oxidase inhibitor eGFR |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.634932/full |
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