The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications

Li, Delun; Yuan, Siyu; Deng, Yiyao; Wang, Xiaowan; Wu, Shouhai; Chen, Xuesheng; Li, Yimeng; Ouyang, Jianting; Lin, Danyao; Quan, Haohao; Fu, Xinwen; Li, Chuang; Mao, Wei

doi:10.3389/fimmu.2023.1282890

Cited by 7 publications

(4 citation statements)

References 125 publications

(186 reference statements)

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“…On the one hand, UA can induce cell damage through the activation of inflammatory responses and oxidative stress. On the other hand, UA can also affect the function of the immune system, including leukocyte migration and cytokine production (6). Therefore, UA may play a role in regulating the development of sepsis-induced inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…This finding indicated that the initial serum UA levels during hospitalization should serve as a predictive indicator for the prognosis of sepsis in the pediatric intensive care unit (ICU) (5). Serum UA may play an important role in inflammatory responses, oxidative stress, and immune regulation (6). Inflammation caused an increase in the release of purines within cells, which in turn promoted the production and release of UA (7).…”

Section: Introductionmentioning

confidence: 99%

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Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Qin,

Yang,

Ning

2024

Shock

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Objective Several epidemiological studies have identified a potential link between serum uric acid(UA), gout and sepsis. The primary objective of this study is to delve deeper into this connection, investigating the causal effect of UA and gout on sepsis by applying Mendelian Randomization (MR). Methods The causal relationship was analyzed using data from genome-wide association study(GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Three complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple median method. Horizontal pleiotropy was identified by MR-Egger intercept test. Cochran’s Q statistics were employed to assess the existence of instrument heterogeneity. The leave-one-out method was used as a sensitivity analysis. Results The IVW results indicated that there was a positive causal relationship between UA and sepsis(critical care) (OR = 0.24, 95%CI: 0.04 to 0.43, P = 0.018, F = 4291.20). There was no significant association between UA and sepsis(28 day death in critical care) (OR = 0.10, 95%CI: -0.29 to 0.50, P = 0.604). There was no significant association between gout and sepsis(critical care) (OR = 0.85, 95%CI: -4.87 to 6.57, P = 0.771), and sepsis(28 day death in critical care) (OR = -6.30, 95%CI: -17.41 to 4.81, P = 0.267). Horizontal pleiotropy was absent in this study. The results were robust under all sensitivity analyses. Conclusion The study revealed that elevated UA levels was causally linked with sepsis(critical care). No causal relationship had been found between UA and sepsis(28 day death in critical care), as well as between gout and sepsis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Qin,

Yang,

Ning

2024

Shock

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“…Dehydration and acidic urinary pH also favour the precipitation of urate, obstructing the collecting ducts and increasing intrarenal pressure, with a reduction in blood flow and renal glomerular filtration rate (GFR) [ 11 , 12 ]. Tissues damaged by crystals act as a lure for the initiation of the inflammatory response and, ultimately, cell death [ 13 , 14 , 15 ]. In addition to obstruction and oxidative stress, UA causes endothelial dysfunction due to a reduction in nitric oxide, renal vasoconstriction, loss of autoregulation, activation of angiotensin II, reduction in glomerular filtration, hypertension, renal ischaemia and activation of the immune system [ 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario

Melero,

Torroba-Sanz,

Goicoechea

et al. 2024

IJMS

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Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.

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“…In immune cells, high uric acid is shown to promote ferroptosis of immune cells. Uric acid crystals can accumulate in target organs, leading to the development of systematic inflammation, activation of immune cells and induce oxidative stress ( 4 , 5 ). Burnier discussed in the current research topic the role of gout and hyperuricaemia and their epidemiological and genetic associations with CVDs.…”

mentioning

confidence: 99%

Editorial: The interplay between oxidative stress, immune cells and inflammation in cardiovascular diseases

Nosalski,

Siedlinski,

Neves

et al. 2024

Front. Cardiovasc. Med.

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The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications

Cited by 7 publications

References 125 publications

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario

Editorial: The interplay between oxidative stress, immune cells and inflammation in cardiovascular diseases

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