Update on the epidemiology, genetics, and therapeutic options of hyperuricemia

Abstract

Hyperuricemia may occur when there is an excess of uric acid in the blood. Hyperuricemia may result from increased production or decreased excretion of uric acid. Elevated uric acid levels are a risk factor for gout, and various risk factors, including some medications, alcohol consumption, kidney disease, high blood pressure, hypothyroidism, and pesticide exposure, as well as obesity, are associated with an elevated risk of hyperuricemia. Although the mechanisms underlying the pathogenesis of hyperuricemia are complex, previously reported studies have revealed that hyperuricemia is involved in a variety of biological processes and signaling pathways. In this review, we summarize common comorbidities related to hyperuricemia and describe an update of epidemiology, pathogenesis, and therapeutic options of hyperuricemia. This systematic review highlights the epidemiology and risk factors of hyperuricemia. Moreover, we discuss genetic studies on hyperuricemia to uncover current status and advances in the pathogenesis of hyperuricemia. Additionally, we conclude with a reflection on the underlying mechanisms of hyperuricemia and present the alternative drug strategies for the treatment of hyperuricemia to offer more effective clinical interventions.

Keywords: Hyperuricemia; epidemiology; genetics; mechanisms; treatment.

Figure 1

Mechanisms of hyperuricemia. HPRT, Hypoxanthine-guanine phosphoribosyltransferase; PRS, Phosphoribosylpyrophosphate synthetase.

Figure 2

Urate transporters in humans. Overproduction and underexcretion of urate result in hyperuricemia. Underexcretion of urate occurs mainly in the proximal renal tubules. Urate overproduction in the liver and underexcretion of urate in the gut may lead to the occurrence of hyperuricemia. In the gut, Genetic variants in ABCG2 inhibit the excretion of urate and promote underexcretion. Numerous transmembrane transporters, such as ABCG2, URAT1, and GLUT9, have crucial roles in urate reuptake and secretion. OAT, organic anion transporter; NPT1, sodium-dependent phosphate cotransporter type 1; ABCG2, ABC transporter G family member 2; URAT1, urate anion exchanger 1; GLUT9, glucose transporter type 9; ABCC4, ATP-binding cassette sub-family C member 4.

Figure 3

Mechanism of urate-lowering therapy for hyperuricemia. Numerous agents can be applied to inhibit urate production, promote renal urate excretion, and increase purine metabolism to allantoin.