ArticleScientific reports2020
Cardio-renal protective effect of the xanthine oxidase inhibitor febuxostat in the 5/6 nephrectomy model with hyperuricemia.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Urate-lowering therapy for CKD patients with asymptomatic hyperuricemia without proteinuria elucidated by attribute-based research in the FEATHER Study.Scientific reports · 2022Trial
- Isobavachin Attenuates Renal and Cardiac Injury in Chronic Hyperuricemia via Modulation of NF-κB and NLRP3 Signaling Pathways.Journal of biochemical and molecular toxicology · 2026Article
- Multiscale Imaging of Human Adipose Tissue: A Neglected Partner in Proteinuria Linked to Obesity.Biomedicines · 2025Review
- Effects of febuxostat on heart failure patients with asymptomatic hyperuricaemia: a retrospective cohort study.BMJ open · 2025Article
- Overview of pharmacodynamical research of traditional Chinese medicine on hyperuricemic nephropathy: from the perspective of dual-regulatory effect on the intestines and kidneys.Frontiers in pharmacology · 2025Review
- Hyperuricemia-induced complications: dysfunctional macrophages serve as a potential bridge.Frontiers in immunology · 2025Review
- The Role of Hyperuricemia in Cardiac Diseases: Evidence, Controversies, and Therapeutic Strategies.Biomolecules · 2024Review
- Metabolomics Assessment of Volume Overload-Induced Heart Failure and Oxidative Stress in the Kidney.Metabolites · 2023Article
- Cardiomyopathy in chronic kidney disease: clinical features, biomarkers and the contribution of murine models in understanding pathophysiology.Clinical kidney journal · 2023Review
- The potential relationship of coronary artery disease and hyperuricemia: A cardiometabolic risk factor.Heliyon · 2023Review
- Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD.Antioxidants (Basel, Switzerland) · 2022Article
- Sex Differences in Time-Series Changes in Pseudo-Journal of personalized medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although hyperuricemia has been shown to be associated with the progression of cardiovascular disorder and chronic kidney disease (CKD), there is conflicting evidence as to whether xanthine oxidase (XO) inhibitors confer organ protection besides lowering serum urate levels. In this study, we addressed the cardio-renal effects of XO inhibition in rodent CKD model with hyperuricemia. Sprague-Dawley rats underwent 5/6 nephrectomy and received a uricase inhibitor oxonic acid for 8 weeks (RK + HUA rats). In some rats, a XO inhibitor febuxostat was administered orally. Compared with control group, RK + HUA group showed a significant increase in albuminuria and renal injury. Febuxostat reduced serum uric acid as well as urinary albumin levels. Histological and immunohistochemical analysis of the kidney revealed that febuxostat alleviated glomerular, tubulointerstitial, and arteriolar injury in RK + HUA rats. Moreover, in the heart, RK + HUA showed individual myofiber hypertrophy and cardiac fibrosis, which was significantly attenuated by febuxostat. We found that renal injury and the indices of cardiac changes were well correlated, confirming the cardio-renal interaction in this model. Finally, NF-E2-related factor 2 (Nrf2) and the downstream target heme oxygenase-1 (HO-1) protein levels were increased both in the heart and in the kidney in RK + HUA rats, and these changes were alleviated by febuxostat, suggesting that tissue oxidative stress burden was attenuated by the treatment. These data demonstrate that febuxostat protects against cardiac and renal injury in RK + HUA rats, and underscore the pathological importance of XO in the cardio-renal interaction.
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