Roles of Serum NLRP3 Inflammasome and Associated Cytokines in Gout-Induced Kidney Injury.

IF 2.3 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Kidney & blood pressure research Pub Date : 2025-01-01 Epub Date: 2025-04-21 DOI:10.1159/000545492

Xiaoqing Xu, Juanjuan Zhang, Yanqun Wu

{"title":"Roles of Serum NLRP3 Inflammasome and Associated Cytokines in Gout-Induced Kidney Injury.","authors":"Xiaoqing Xu, Juanjuan Zhang, Yanqun Wu","doi":"10.1159/000545492","DOIUrl":null,"url":null,"abstract":"Introduction: Gout, characterized by hyperuricemia and urate crystal deposition, is associated with systemic inflammatory complications, including kidney injury. This study aimed to investigate the role of serum nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome and associated cytokines (IL-1β and IL-18) in gout-related kidney injury (GRI).Methods: A total of 279 gout patients (96 with renal injury and 183 without renal injury) and 100 healthy controls were included. Serum NLRP3, IL-1β, and IL-18 were measured and compared using an enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was carried out to evaluate the diagnostic values of individual or combinational biomarkers. Spearman's correlation analysis was employed to analyze correlations between NLRP3, IL-1β, and IL-18 and renal function indicators or serum uric acid.Results: Serum levels of NLRP3, IL-1β, and IL-18 were significantly higher in gout patients compared to healthy controls (p < 0.001, gout group with kidney injury [GKI]: n = 96, gout group without kidney injury [GNKI]: n = 183, controls: n = 100), with elevated levels observed in GKI patients compared to GNKI (p < 0.001). Correlations between these markers were confirmed among all gout patients (n = 279), including serum NLRP3 with IL-1β (r = 0.34, p < 0.001) and NLRP3 with IL-18 (r = 0.47, p < 0.001). ROC analysis revealed that the combined model of NLRP3, IL-1β, and IL-18 showed improved diagnostic accuracy for GRI, with an AUC of 0.85 (95% CI: 0.81-0.89, p < 0.001). In GKI patients (n = 96), serum NLRP3, IL-1β, and IL-18 were inversely correlated with eGFR (NLRP3: r = -0.43, p < 0.01). Additionally, serum IL-18 positively correlated with serum uric acid levels (r = 0.27, p = 0.009).Conclusion: These findings highlight the potential of serum NLRP3, IL-1β, and IL-18 as diagnostic markers and therapeutic targets in GRI, providing insights into early intervention and improved clinical outcomes in gout patients with renal complications.","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"341-350"},"PeriodicalIF":2.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney & blood pressure research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000545492","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/21 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Gout, characterized by hyperuricemia and urate crystal deposition, is associated with systemic inflammatory complications, including kidney injury. This study aimed to investigate the role of serum nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome and associated cytokines (IL-1β and IL-18) in gout-related kidney injury (GRI).

Methods: A total of 279 gout patients (96 with renal injury and 183 without renal injury) and 100 healthy controls were included. Serum NLRP3, IL-1β, and IL-18 were measured and compared using an enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was carried out to evaluate the diagnostic values of individual or combinational biomarkers. Spearman's correlation analysis was employed to analyze correlations between NLRP3, IL-1β, and IL-18 and renal function indicators or serum uric acid.

Results: Serum levels of NLRP3, IL-1β, and IL-18 were significantly higher in gout patients compared to healthy controls (p < 0.001, gout group with kidney injury [GKI]: n = 96, gout group without kidney injury [GNKI]: n = 183, controls: n = 100), with elevated levels observed in GKI patients compared to GNKI (p < 0.001). Correlations between these markers were confirmed among all gout patients (n = 279), including serum NLRP3 with IL-1β (r = 0.34, p < 0.001) and NLRP3 with IL-18 (r = 0.47, p < 0.001). ROC analysis revealed that the combined model of NLRP3, IL-1β, and IL-18 showed improved diagnostic accuracy for GRI, with an AUC of 0.85 (95% CI: 0.81-0.89, p < 0.001). In GKI patients (n = 96), serum NLRP3, IL-1β, and IL-18 were inversely correlated with eGFR (NLRP3: r = -0.43, p < 0.01). Additionally, serum IL-18 positively correlated with serum uric acid levels (r = 0.27, p = 0.009).

Conclusion: These findings highlight the potential of serum NLRP3, IL-1β, and IL-18 as diagnostic markers and therapeutic targets in GRI, providing insights into early intervention and improved clinical outcomes in gout patients with renal complications.

查看原文本刊更多论文

血清NLRP3炎性体及相关细胞因子在痛风所致肾损伤中的作用。

痛风以高尿酸血症和尿酸盐晶体沉积为特征，与包括肾损伤在内的全身性炎症并发症相关。本研究旨在探讨血清核苷酸结合寡聚结构域样受体3 （NLRP3）炎症小体和相关细胞因子（IL-1β和IL-18）在痛风相关性肾损伤（GRI）中的作用。方法：279例痛风患者（有肾损伤96例，无肾损伤183例）和健康对照100例。采用酶联免疫吸附法测定血清NLRP3、IL-1β和IL-18并进行比较。进行受试者工作特征（ROC）分析以评估单个或组合生物标志物的诊断价值。采用Spearman相关分析分析NLRP3、IL-1β、IL-18与肾功能指标或血清尿酸的相关性。结果：痛风患者血清NLRP3、IL-1β和IL-18水平显著高于健康对照组[p < 0.001，痛风合并肾损伤组（GKI）： n = 96，痛风无肾损伤组（GNKI）： n = 183，对照组：n = 100]， GKI患者血清NLRP3、IL-1β和IL-18水平高于GNKI患者（p < 0.001）。所有痛风患者（n = 279）均证实了这些标志物之间的相关性，包括血清中含有IL-1β的NLRP3 （r = 0.34, p < 0.001）和含有IL-18的NLRP3 （r = 0.47, p < 0.001）。ROC分析显示，NLRP3、IL-1β和IL-18联合模型对GRI的诊断准确性提高，AUC为0.85 （95% CI: 0.81-0.89, p < 0.001）。GKI患者（96例）血清NLRP3、IL-1β、IL-18与eGFR呈负相关（NLRP3: r = -0.43, p < 0.01）。此外，血清IL-18与血清尿酸水平呈正相关（r = 0.27, p = 0.009）。结论：这些发现突出了血清NLRP3、IL-1β和IL-18作为GRI诊断标志物和治疗靶点的潜力，为早期干预和改善伴有肾脏并发症的痛风患者的临床结果提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.