Uric acid as a cardiorenal mediator: pathogenesis and mechanistic insights

ABSTRACT

Introduction: The role of serum uric acid as a connector in cardiorenal interactions has been long debated and studied extensively in the past decade. Epidemiological, and clinical data suggest that hyperuricemia may be an independent risk factor as well as a strong predictor of morbidity and mortality in cardiovascular diseases (CVD) and renal diseases. New data suggesting that urate lowering therapies may improve outcomes in cardiovascular diseases have generated interest.

Areas Covered: This review attempts to summarize the pathophysiological mechanisms by which hyperuricemia causes cardiorenal dysfunction. It also provides a summary of the recent evidence for urate lowering therapies and the possible underlying mechanisms which lead to cardiovascular benefits. This was a narrative review with essential references or cross references obtained via expert opinion.

Expert Opinion: Emphasis on newer drugs that address the cardio-renal metabolic axis and the relation to their effects on uric acid may help further elucidate underlying mechanisms responsible for their cardiovascular and renal benefits. Once these benefits are well established, we will be able to come up with guidelines for targeting hyperuricemia. This can potentially lead to a change in clinical practice and can possibly lead to improved cardiovascular and renal outcomes.

KEYWORDS:

• Heart failure
• hyperuricemia
• cardiovascular disease
• chronic kidney disease

Article highlights

• Uric Acid is a strong mediator of both cardiovascular and renal diseases.

• Hyperuricemia has been implicated in both worsening heart failure as well as worsening of kidney dysfunction.

• SUA reduction by XO inhibitors has shown conflicting evidence in terms of benefits in patients with heart failure.

• SGLT-2 inhibitors have shown evidence of shown cardiovascular benefits and may exert these beneficial outcomes by lowering levels of SUA.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.