Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients
Abstract Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads t...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26519-x |
| _version_ | 1797952528362504192 |
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| author | Yuki Ohashi Masao Toyoda Nobumichi Saito Masahiro Koizumi Genta Kanai Hirotaka Komaba Moritsugu Kimura Takehiko Wada Hiroo Takahashi Yuichiro Takahashi Naoto Ishida Takatoshi Kakuta Masafumi Fukagawa Kimiyoshi Ichida |
| author_facet | Yuki Ohashi Masao Toyoda Nobumichi Saito Masahiro Koizumi Genta Kanai Hirotaka Komaba Moritsugu Kimura Takehiko Wada Hiroo Takahashi Yuichiro Takahashi Naoto Ishida Takatoshi Kakuta Masafumi Fukagawa Kimiyoshi Ichida |
| author_sort | Yuki Ohashi |
| collection | DOAJ |
| description | Abstract Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction. |
| first_indexed | 2024-04-10T22:47:48Z |
| format | Article |
| id | doaj.art-0e483fa5cdb84734b9795fd2b63716f9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T22:47:48Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0e483fa5cdb84734b9795fd2b63716f92023-01-15T12:12:00ZengNature PortfolioScientific Reports2045-23222023-01-0113111110.1038/s41598-022-26519-xEvaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patientsYuki Ohashi0Masao Toyoda1Nobumichi Saito2Masahiro Koizumi3Genta Kanai4Hirotaka Komaba5Moritsugu Kimura6Takehiko Wada7Hiroo Takahashi8Yuichiro Takahashi9Naoto Ishida10Takatoshi Kakuta11Masafumi Fukagawa12Kimiyoshi Ichida13Department of Pathophysiology, Tokyo University of Pharmacy and Life SciencesDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Tokai University Oiso HospitalDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineJinken ClinicJinken ClinicSeichi ClinicDivision of Nephrology, Endocrinology and Metabolism, Tokai University Hachioji HospitalDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of MedicineDepartment of Pathophysiology, Tokyo University of Pharmacy and Life SciencesAbstract Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.https://doi.org/10.1038/s41598-022-26519-x |
| spellingShingle | Yuki Ohashi Masao Toyoda Nobumichi Saito Masahiro Koizumi Genta Kanai Hirotaka Komaba Moritsugu Kimura Takehiko Wada Hiroo Takahashi Yuichiro Takahashi Naoto Ishida Takatoshi Kakuta Masafumi Fukagawa Kimiyoshi Ichida Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients Scientific Reports |
| title | Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients |
| title_full | Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients |
| title_fullStr | Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients |
| title_full_unstemmed | Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients |
| title_short | Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients |
| title_sort | evaluation of abcg2 mediated extra renal urate excretion in hemodialysis patients |
| url | https://doi.org/10.1038/s41598-022-26519-x |
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