Hyperuricemia: a novel old disorder—relationship and potential mechanisms in heart failure

Borghi, Claudio; Palazzuoli, Alberto; Landolfo, Matteo; Cosentino, Eugenio Roberto

doi:10.1007/s10741-019-09869-z

Cited by 34 publications

(27 citation statements)

References 91 publications

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“…237 At present, multiple clinical applications of SGLT-2i have emerged, and multiple clinical trials have reported its urate-lowering effect. 238…”

Section: The Therapeutic Strategy Of Hyperuricemiamentioning

confidence: 99%

<p>Converging Relationships of Obesity and Hyperuricemia with Special Reference to Metabolic Disorders and Plausible Therapeutic Implications</p>

Gong¹,

Su²,

Nguyen³

et al. 2020

DMSO

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Background: Obesity and hyperuricemia mutually influence metabolic syndrome. This study discusses the metabolic relationships between obesity and hyperuricemia in terms of pathophysiology, complications, and treatments. Methods: We searched for preclinical or clinical studies on the pathophysiology, complications, and therapy of obesity and hyperuricemia on the PubMed database. Results: In this systemic review, we summarized our searching results on topics of pathophysiology, complications and therapeutic strategy. In pathophysiology, we firstly introduce genetic variations for obesity, hyperuricemia and their relationships by genetic studies. Secondly, we talk about the epigenetic influences on obesity and hyperuricemia. Thirdly, we describe the central metabolic regulation and the role of hyperuricemia. Then, we refer to the character of adipose tissue inflammation and oxidative stress in the obesity and hyperuricemia. In the last part of this topic, we reviewed the critical links of gut microbiota in the obesity and hyperuricemia. In the following part, we review the pathophysiology of major complications in obesity and hyperuricemia including insulin resistance and type 2 diabetes mellitus, chronic kidney disease, cardiovascular diseases, and cancers. Finally, we recapitulate the therapeutic strategies especially the novel pharmaceutic interventions for obesity and hyperuricemia, which concurrently show the mutual metabolic influences between two diseases. Conclusion: The data reviewed here delineate the metabolic relationships between obesity and hyperuricemia, and provide a comprehensive overview of the therapeutic targets for the management of metabolic syndromes.

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“…237 At present, multiple clinical applications of SGLT-2i have emerged, and multiple clinical trials have reported its urate-lowering effect. 238…”

Section: The Therapeutic Strategy Of Hyperuricemiamentioning

confidence: 99%

<p>Converging Relationships of Obesity and Hyperuricemia with Special Reference to Metabolic Disorders and Plausible Therapeutic Implications</p>

Gong¹,

Su²,

Nguyen³

et al. 2020

DMSO

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“…have concluded, that higher SUA levels in patients with DM type 1 are associated with a higher risk of CV events, mortality, and kidney function decline, independently of other factors [ 61 ]. A recent review has additionally highlighted the importance of SUA on development and clinical prognosis of heart failure, where drugs that are associated with improved CV outcomes such as SGLT2 inhibitors and ARNI, also presented an SUA lowering capability [ 62 ].…”

Section: Hyperuricemia and Cardiovascular Diseasementioning

confidence: 99%

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

et al. 2020

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Background: Hyperuricemia is a state in which the serum levels of uric acid are elevated. As such it has a pronounced effect on vascular and renal function with their consequences, while also showing some antioxidant effects that show to be beneficial. Summary: Hyperuricemia has shown to have a J-shaped relationship with mortality, is frequently associated with development and progression of heart and kidney disease, and is correlated with malnutrition-inflammation-atherosclerosis syndrome, although several Mendelian studies have failed to show an association with morbidity and mortality. Hyperuricemia is usually associated with gout flares and tophi development but can also present as asymptomatic hyperuricemia. It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for cardiovascular or renal disease and as such its treatment is questionable. Key messages: Some possible tools for future decision making are the use of noninvasive techniques such as pulse wave analysis, urinary sediment analysis, and joint ultrasound, which could help identify individuals with asymptomatic hyperuricemia that could benefit from urate lowering therapy most.

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“…Uric acid and its salts are polar compounds but with poor solubility (Iwata et al, 1989). The redundant uric acid and its salts are precipitated in the kidneys, bones and joints as tophi, usually resulting in renal dysfunction and gout (Feig, 2014); however, the relationship between hyperuricemia and other diseases is still unclear (Borghi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Uricase-deficient rat is generated with CRISPR/Cas9 technique

Zhang

Dong

et al. 2020

PeerJ

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Urate oxidase (uricase, Uox) is a big obstacle for scientists to establish stable animal models for studying hyperuricemia and associated disorders. Due to the low survival rate of uricase-deficient mice, we generated a Uox-knockout model animal from Sprague Dawley (SD) rats using the CRISPR/Cas9 technique by deleting exons 2 to 4 of the Uox gene. The uricase-deficient rats were named “Kunming-DY rats”, and were apparently healthy with more than a 95% survival up to one year. The male rats’ serum uric acid (SUA) increased to 48.3 ± 19.1 µg/ml, significantly higher than those of wild-type rats. Some indexes of the blood fat like total triglyceride, low density lipoprotein, and renal function indexes including blood urea nitrogen and serum creatinine were significantly different from those of wild-type rats, however, all the indexes were close to or in normal ranges. Histological renal changes including mild glomerular/tubular lesions were observed in these uricase-deficient rats. Thus, “Kunming-DY rats” with stable uricase-deficiency were successfully established and are an alternative model animal to study hyperuricemia and associated diseases mimicking human conditions.

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Hyperuricemia: a novel old disorder—relationship and potential mechanisms in heart failure

Cited by 34 publications

References 91 publications

<p>Converging Relationships of Obesity and Hyperuricemia with Special Reference to Metabolic Disorders and Plausible Therapeutic Implications</p>

<p>Converging Relationships of Obesity and Hyperuricemia with Special Reference to Metabolic Disorders and Plausible Therapeutic Implications</p>

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

Uricase-deficient rat is generated with CRISPR/Cas9 technique

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