The Long-Term Effects of the Selective Inhibitor of Urate Transporter 1, Dotinurad, on Metabolic Parameters and Renal Function in Japanese Patients With Asymptomatic Hyperuricemia
Bibliographic record
Abstract
Background: Epidemiological studies have reported that hyperuricemia is associated with the development of metabolic syndrome, hypertension, dyslipidemia, type 2 diabetes, and chronic kidney disease (CKD). Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) in renal proximal tubule epithelial cells. Recently, URAT1 was found to be expressed in the liver and adipose tissue in addition to the kidney. UA enters such organs via URAT1 and induces inflammation and oxidative stress, which may lead to metabolic disorders. We investigated the effects of long-term treatment with the novel uricosuric drug, a highly selective inhibitor of URAT1, dotinurad, on metabolic parameters and renal function. Methods: We retrospectively picked up patients who had taken dotinurad for the treatment of asymptomatic hyperuricemia for more than 2 years. We compared metabolic parameters and renal function at baseline with the data at 6, 12, 18, and 24 months after starting dotinurad. Results: Pharmacologically, dotinurad decreases serum UA, by selectively inhibiting URAT1 and decreasing renal reabsorption of UA, which was supported by our result that dotinurad significantly increased urine UA and reduced serum UA. In addition to UA-lowering, dotinurad was associated with improvements in body weight, liver function, hepatic steatosis index as the marker for metabolic dysfunction-associated steatotic liver disease (MASLD), serum lipids, and albuminuria. The ATP-binding cassette transporter G2 (ABCG2) regulates renal and intestinal excretion of UA and uremic toxins and strongly affects renal function. Our study also indicates that switching from xanthine oxidase inhibitors, which inhibit ABCG2, to dotinurad, which does not inhibit ABCG2, was beneficial for albuminuria and maintaining the estimated glomerular filtration rate. Conclusion: Dotinurad may improve obesity, MASLD, serum lipids, and CKD by blocking the entry of UA via URAT1 to the adipose tissue, liver, and kidney.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".