Serum Uric Acid and the Risk of Incident and Recurrent Gout: A Systematic Review

Shiozawa, Aki; Szabo, Shelagh M.; Bolzani, Anna; Cheung, Antoinette; Choi, Hyon K.

doi:10.3899/jrheum.160452

Cited by 122 publications

(72 citation statements)

References 37 publications

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“…Gout is known to be a disease where the deposition of urate crystals is continuous, while the flares are intermittent . Moreover, the higher the urate load, the more frequent the acute attacks are known to occur . It is tempting to speculate that MSU crystals could also prime circulating or resident cells for elevated inflammatory responses via innate immune memory‐like mechanisms.…”

Section: Urate‐induced Immune Programmingmentioning

confidence: 58%

“…5 Moreover, the higher the urate load, the more frequent the acute attacks are known to occur. 107 It is tempting to speculate that MSU crystals could also prime circulating or resident cells for elevated inflammatory responses via innate immune memory-like mechanisms. Indeed, one study did show that MSU crystals were able to enhance the phagocytosis and killing capacity of murine macrophages leading to a more enduring response to BCG vaccination in mice.…”

Section: Urate Crystal-dependent Inflammation and Epigenetic Regulamentioning

confidence: 99%

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Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia

Cabău

Crişan

Klück

et al. 2019

Immunological Reviews

140

110

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Trained immunity is a process in which innate immune cells undergo functional reprogramming in response to pathogens or damage‐associated molecules leading to an enhanced non‐specific immune response to subsequent stimulation. While this capacity to respond more strongly to stimuli is beneficial for host defense, in some circumstances it can lead to maladaptive programming and chronic inflammation. Gout is characterized by persistent low‐grade inflammation and is associated with an increased number of comorbidities. Hyperuricemia is the main risk factor for gout and is linked to the development of comorbidities. Several experimental studies have shown that urate can mechanistically alter the inflammatory capacity of myeloid cells, while observational studies have indicated an association of hyperuricemia to a wide spectrum of common adult inflammatory diseases. In this review, we argue that hyperuricemia is a main culprit in the development of the long‐term systemic inflammation seen in gout. We revisit existing evidence for urate‐induced transcriptional and epigenetic reprogramming that could lead to an altered functional state of circulating monocytes consisting in enhanced responsiveness and maladaptive immune responses. By discussing specific functional adaptations of monocytes and macrophages induced by soluble urate or monosodium urate crystals and their contribution to inflammation in vitro and in vivo, we further enforce that urate is a metabolite that can induce innate immune memory and we discuss future research and possible new therapeutic approaches for gout and its comorbidities.

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Section: Urate‐induced Immune Programmingmentioning

confidence: 58%

Section: Urate Crystal-dependent Inflammation and Epigenetic Regulamentioning

confidence: 99%

Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia

Cabău

Crişan

Klück

et al. 2019

Immunological Reviews

140

110

View full text Add to dashboard Cite

show abstract

“…A number of variables contribute to the risk of progressive disease, with serum urate levels being the most important variable identified to date [43]. However, serum urate levels alone do not reliably predict progression of disease.…”

Section: Translation Of Genetic Discoveries Into Clinical Practice: Tmentioning

confidence: 99%

The genetics of gout: towards personalised medicine?

Dalbeth

Stamp

Merriman

2017

BMC Med

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Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

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“…По данным систематизированного обзора популяционных проспективных исследований, частота развития подагры варьировалась от 3 случаев на 1000 пациенто-лет при сывороточном уровне мочевой кислоты <6 мг/дл до 70 случаев на 1000 пациенто-лет при повышении уровня мочевой кислоты >10 мг/дл. Сходные результаты были получены при анализе частоты рецидивирования подагры, которая достигала 60-90% при гиперурикемии более 9 мг/дл [9]. Даже при отсутствии симптомов у 15-25% пациентов с гиперурикемией можно выявить отложение кристаллов моноурата натрия [7].…”

Section: диагностика подагрыunclassified

Canakinumab for the treatment of recurrent gouty arthritis

Moiseev¹,

Novikov²,

Рамеев³

2019

CPT

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Ключевую роль в развитии острого подагрического артрита играет активация NLRP3 инфламмасомы под действием кристаллов моноурата натрия. В состав инфламмасомы входит прокаспаза-1, которая превращается в активную каспазу-1, вызыващую секрецию интерлейкина (ИЛ-1β)основного провоспалительного цитокина, индуцирующего острый воспалительный ответ. Канакинумаб -это человеческие моноклональные IgG1 антитела к интерлейкину (ИЛ)-1β, которые связываются с цитокином и блокируют его взаимодействие с рецепторами. В двух рандомизированных клинических исследованиях 3 фазы канакинумаб (одна инъекция 150 мг подкожно) превосходил триамцинолона ацетонид по эффективности в лечении острого подагрического артрита у пациентов с частыми приступами подагры. Лечение канакинумабом по сравнению с глюкокортикостероидом привело к значительному увеличению времени до первого обострения и снижению риска обострений на 62% за 12 недель. Применение канакинумаба у пациентов с острым подагрическим артритом обосновано при наличии противопоказаний к назначению нестероидных противовоспалительных препаратов и/или колхицина, недостаточной их эффективности или плохой переносимости.Ключевые слова. Острый подагрический артрит, интерлейкин-1β, канакинумаб.

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Serum Uric Acid and the Risk of Incident and Recurrent Gout: A Systematic Review

Cited by 122 publications

References 37 publications

Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia

Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia

The genetics of gout: towards personalised medicine?

Canakinumab for the treatment of recurrent gouty arthritis

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