A glance into the future of gout

Abstract

Gout is characterized by monosodium urate (MSU) crystal deposits in and within joints. These deposits result from persistent hyperuricaemia and most typically lead to recurrent acute inflammatory episodes (gout flares). Even though some aspects of gout are well characterized, uncertainties remain; this upcoming decade should provide further insights into many of these uncertainties. Synovial fluid analysis allows for the identification of MSU crystals and unequivocal diagnosis. Non-invasive methods for diagnosis are being explored, such as Raman spectroscopy and imaging modalities. Both ultrasound and dual-energy computed tomography (DECT) allow the detection of MSU crystals; this not only provides a mean of diagnosis, but also has furthered gout knowledge defining the presence of a preclinical deposition in asymptomatic hyperuricaemia. Scientific consensus establishes the beginning of gout as the beginning of symptoms (usually the first flare), but the concept is currently under review. For effective long-term gout management, the main goal is to promote crystal dissolution treatment by reducing serum urate below 6 mg/dL (or 5 mg/dL if faster crystal dissolution is required). Current urate-lowering therapies’ (ULTs) options are limited, with allopurinol and febuxostat being widely available, and probenecid, benzbromarone, and pegloticase available in some regions. New xanthine oxidase inhibitors and, especially, uricosurics inhibiting urate transporter URAT1 are under development; it is probable that the new decade will see a welcomed increase in the gout therapeutic armamentarium. Cardiovascular and renal comorbidities are common in gout patients. Studies determining whether optimal treatment of gout will positively impact these comorbidities are currently lacking, but will hopefully be forthcoming. Overall, the single change that will most impact gout management is greater uptake of international rheumatology society recommendations. Innovative strategies, such as nurse-led interventions based on these recommendations have recently demonstrated treatment success for people with gout.

The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics

“…In certain states (fasting) and with certain medicines (thiazide diuretics, favipiravir), SUA concentration can increase ( Zhang, 2021 ). Furthermore, renal insufficiency patients have difficulty maintaining normal urate levels due to damaged renal urate transport proteins ( Sivera, Andres & Dalbeth, 2022 ).…”

“…Reduced urate levels result in the crystals gradually dissolving, thus improving gout sufferers’ outcomes. In general, ULT options consist of reducing urate synthesis (allopurinol and febuxostat), increasing renal urate excretion (benzbromarone and probenecid), and using uricase ( Sivera, Andres & Dalbeth, 2022 ). Asymptomatic hyperuricemia therapy has attracted attention in addition to the therapeutic management of gout patients.…”

“…An analysis of retrospective data in China showed that SUA levels were associated with rapid glomerular filtration rate declines ( Zhou et al, 2019 ). As SUA levels rise, urate crystals form in the renal tubules and interstitial spaces, ultimately causing renal damage ( Sivera, Andres & Dalbeth, 2022 ; Su et al, 2020 ). A high purine diet or excessive intake of fructose and alcohol can induce the degradation of purine nucleotides, leading to the production of UA ( Zhang, Jiao & Kong, 2017 ).…”

Evaluation of the efficacy and safety of pegloticase for the treatment of chronic refractory gout through meta-analysis

“…Given that more than 40% of patients develop antibodies against pegloticase, strategies for delivering pegloticase are being reassessed (11). Methotrexate has been the most investigated agent as a drug that reduces the tolerability of pegloticase.…”

A Brief Review of Natural Products with Urate Transporter 1 Inhibition for the Treatment of Hyperuricemia

“…Due to the great potential of URAT1 inhibitors in the treatment of hyperuricemia and gout, researchers have been exploring new URAT1 inhibitors [38]. As an important source of new drugs, natural products have received more and more attention for their inhibitory effects on URAT1 [39].…”