Urece (dotinurad) / Fuji Yakuhin, Mochida, Fortress, Eisai - LARVOL DELTA

POTENTIAL NEPHROPROTECTION WITH NOVEL URAT1 INHIBITOR DOTINURAD: A SYSTEMATIC REVIEW OF KIDNEY FUNCTION CHANGES (ISN-WCN 2026) - "Unlike traditional agents such as allopurinol or febuxostat, preliminary clinical observations suggest dotinurad may offer unique renoprotective properties beyond urate reduction. Dedicated randomized controlled trials with eGFR as the primary endpoint are urgently needed, particularly with CKD stage-stratified analyses, long-term outcomes (>1 year), and establishment of optimal patient selection criteria. This review provides crucial preliminary evidence to inform such trial designs."

Review • Chronic Kidney Disease • Inflammation • Renal Disease

EFFECT OF DOTINURAD VERSUS FEBUXOSTAT ON THE ONE-YEAR EGFR SLOPE IN CKD PATIENTS WITH HYPERURICEMIA: A RETROSPECTIVE COHORT STUDY (ISN-WCN 2026) - "The within-group change in eGFR slope (post minus pre) was +4.2 ml/min/1.73 m2/year for dotinurad (p = 0.021) and −0.5 ml/min/1.73 m2/year for febuxostat (p = 0.731).Conclusion In this real-world cohort of CKD patients with hyperuricemia, initiation of dotinurad was associated with a significantly greater improvement in kidney function slope compared with febuxostat, even after adjustment for major confounders. These findings suggest that dotinurad, a selective urate reabsorption inhibitor, may confer renal benefits distinct from xanthine oxidase inhibitors, supporting the importance of the mechanism of urate lowering in CKD management"

Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hypertension • Metabolic Disorders • Nephrology • EGFR

RENOPROTECTIVE EFFECT OF DOTINURAD IN PATIENTS WITH HYPERURICEMIA: A SINGLE-CENTER RETROSPECTIVE COHORT STUDY (ISN-WCN 2026) - "However, no improvement in proteinuria was observed. Given the single-center design and small sample size, further multicenter prospective studies are warranted to confirm these findings and elucidate the mechanisms underlying the renoprotective effects of dotinurad."

Retrospective data • Renal Disease

LOW-DOSE DOTINURAD, A NOVEL URIC ACID-LOWERING AGENT THAT PROMOTES URIC ACID SECRETION, IS AN EFFECTIVE TREATMENT FOR MODERATE TO ADVANCED CHRONIC KIDNEY DISEASE (ISN-WCN 2026) - "Interestingly, the urine became alkalized, indicating that this agent may also inhibit the production of urinary stones. In the future, we need to increase the number of people involved and conduct further research."

Metastases • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Gout • Hypertension • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

Industry Symposium 3: Uric Acid and Kidney Disease (ISN-WCN 2026) - "In Japan, dotinurad, a selective uric acid reabsorption inhibitor, is available for use. Its efficacy is attracting attention as it does not affect other uric acid transporters.Learning Objectives: This seminar will provide an overview from two experts, incorporating their own case studies, on the relationship between uric acid and renal impairment, its physiology and pathophysiology, as well as the classification of hyperuricaemia subtypes and the types and selection of urate-lowering drugs."

Chronic Kidney Disease • Nephrology • Renal Disease

COMPARATIVE EFFICACY AND SAFETY OF DOTINURAD AND FEBUXOSTAT IN GOUT PATIENTS WITH UNDEREXCRETION-TYPE HYPERURICEMIA: A POST-HOC ANALYSIS OF THE MULTICENTER, DOUBLE-BLIND, PHASE 3 TRIAL NCT05007392 (EULAR 2026) - P3 | No abstract available

Clinical • P3 data • Retrospective data • Gout • Inflammatory Arthritis • Rheumatology

FYU-981-CRYS-301: Phase 3 Study of Dotinurad vs Allopurinol in Participants With Gout (clinicaltrialsregister.eu) - P2/3 | N=65 | Recruiting | Sponsor: Crystalys Therapeutics Inc.

New P2/3 trial • Gout • Inflammatory Arthritis • Rheumatology

Changes in uric acid levels and estimated glomerular filtration rate slope after treatment with dotinurad in patients with hyperuricemia. (PubMed, BMC Nephrol) - No abstract available

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Research progress on multidimensional intervention strategies for hyperuricemia: Western medicine, Traditional Chinese Medicine, and emerging therapies. (PubMed, Front Endocrinol (Lausanne)) - "This article systematically reviews the current various intervention methods and research status for the treatment of hyperuricemia: In the field of Western medicine, it deeply analyzes the efficacy, mechanism of action, and clinical limitations of drugs that promote uric acid excretion (such as benzbromarone and dotinurad), drugs that inhibit uric acid synthesis (such as allopurinol, febuxostat, and topiroxostat), and drugs that promote uric acid hydrolysis (such as pegloticase and rasburicase). It focuses on elaborating the research breakthroughs of URAT1 inhibitor derivatives and the new drug SHR4640...At the same time, it details the action pathways and clinical evidence of emerging therapies such as SGLT2 inhibitors, the GLP-1/GCG dual-receptor agonist Mazdutide, probiotics, and washed microbiota transplantation (WMT). By summarizing mechanistic insights, clinical progress, and translational prospects, this review aims to inform the development of individualized and..."

Journal • Review • Cardiovascular • Gout • Inflammatory Arthritis • Metabolic Disorders • Rheumatology • Transplantation • GCG

Benzoheterocyclic analogues of dotinurad as orally efficacious human urate transporter 1 inhibitors: Design, synthesis, structure-activity relationships, and pharmacokinetic studies. (PubMed, Eur J Med Chem) - "Mechanistic investigation revealed that the substantial excretion of unchanged prototype compounds into the urine ensured a high local concentration within the renal tubule lumen, which effectively compensated for their moderate in vitro affinity. These findings validated the design strategy and highlighted compounds 9, 13, and 14 as promising candidates for hyperuricemia treatment."

Journal • PK/PD data

Effectiveness and Safety of the Novel Selective Urate Reabsorption Inhibitor Dotinurad After Switching from Febuxostat in Patients with Stage B/C Heart Failure. (PubMed, Drugs Real World Outcomes) - "Switching from febuxostat to dotinurad may be effective and safe over the short term in patients with Stage B/C heart failure and hyperuricemia."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Gout • Heart Failure • Inflammatory Arthritis • Nephrology • Renal Calculi • Renal Disease • Rheumatology • Urolithiasis

Effect of Dotinurad on Uric Acid and Hepatorenal Parameters in Steatotic Liver Disease: A Pilot Study in Japanese Patients. (PubMed, Biomedicines) - " DOT effectively reduced serum uric acid and modestly improved renal and hepatobiliary parameters in HU-SLD without any patient-reported complications. These real-world findings support the potential of DOT as a well-tolerated therapeutic option beyond urate lowering and warrant further investigation in larger, controlled studies."

Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Switching from febuxostat to dotinurad, a novel selective urate reabsorption inhibitor, may substantially reduce serum urate levels, through URAT1 inhibition, potentially without adversely affecting ABCG2 function: findings from the SWITCH SURI study. (PubMed, Front Endocrinol (Lausanne)) - "Switching to dotinurad was significantly reduced serum urate levels via URAT1 inhibition, potentially without adversely affecting ABCG2 function, with the majority of patients achieving the target urate level (≤6.0 mg/dL) by week 24. Including the absence of new safety concerns, dotinurad appears to be an effective urate-lowering therapy for patients with type 2 DKD."

Journal • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • ABCG2

A Single- and Multiple-Dose Study to Characterize the Pharmacokinetics and Safety of Dotinurad in Healthy Chinese Adults. (PubMed, Clin Drug Investig) - P1 | "Single- and multiple-dose PK of dotinurad in healthy Chinese adults showed rapid absorption, rapid elimination, linear PK, and no accumulation with once-daily dosing. Dotinurad was well-tolerated during the 7-day treatment course."

Journal • PK/PD data • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Tophaceous Gout (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Crystalys Therapeutics | Trial completion date: Oct 2027 ➔ Dec 2027 | Trial primary completion date: Sep 2027 ➔ Dec 2027

Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Crystalys Therapeutics | Trial primary completion date: Aug 2027 ➔ Nov 2027

Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Crystalys Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Changes in urinary albumin levels with dotinurad oral administration in hyperuricemic patients with microalbuminuria: a post hoc analysis. (PubMed, Clin Exp Nephrol) - P3 | "A significant decrease in UACR following dotinurad administration was observed. Additional RCTs with appropriate control groups are needed to further confirm these findings."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Renal Disease

Efficacy and Safety of Dotinurad in Patients with Advanced Chronic Kidney Disease. (PubMed, Intern Med) - "No adverse events were observed. Conclusion Dotinurad can safely lower serum uric acid levels in hyperuricemic patients with advanced CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: Crystalys Therapeutics

New P3 trial • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Tophaceous Gout (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Crystalys Therapeutics

New P3 trial • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Tophaceous Gout (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Crystalys Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Dotinurad, a novel urate reabsorption inhibitor, prolongs survival in Alport mice. (PubMed, Kidney360) - "These findings suggest that dotinurad may exert renoprotective effects in CKD. Further research is needed to confirm these effects in clinical settings."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Fibrosis • Genetic Disorders • Glomerulonephritis • Gout • Hepatology • Immunology • Inflammatory Arthritis • Liver Failure • Nephrology • Renal Disease • Rheumatology

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. (PubMed, J Clin Med Res) - "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. Dotinurad may improve obesity, MASLD, serum lipids, and CKD by blocking the entry of UA via URAT1 to the adipose tissue, liver, and kidney."

Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus • ABCG2

Dotinurad Treatment for Patients With Hyperuricemia Complicating CKD. (PubMed, Kidney Int Rep) - "Dotinurad therapy may be well-tolerated in patients with hyperuricemia and may have efficacy comparable with existing standard treatment in patients with CKD stages G3/G4. Randomized controlled trials in larger patient groups are needed."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease