Oxidative Stress, Inflammatory Cytokine Levels Associated With Clinical Outcomes in Gout

Oxidative stress and inflammatory cytokine levels may affect the development and clinical manifestations of gout and associated comorbidities.

Oxidative stress and inflammatory cytokine levels may affect the clinical outcomes of patients with gout and associated comorbidities, according to research results published in The Journal of Rheumatology.

Researchers aimed to identify phenotype clusters and pathophysiologic subtypes of patients with gout that may help guide adjunctive treatment.

A clinic-based cross-sectional study was conducted among patients with gout from the University of Alabama at Birmingham from January 2018 to December 2019.

Using the electronic health record system, demographic, clinical and laboratory information were collected. Clinical data included body mass index (BMI), age of onset of gout, tophi, gout flares, urate-lowering therapies (ULTs), number of gout flares, ischemic heart disease, cerebrovascular disease, dyslipidemia, hypertension, diabetes mellitus, and nephrolithiasis.

Oxidative stress and inflammatory markers were also collected and assessed in conjunction with clinical data.

When clustering patients with gout based on clinical data, a total of 3 clusters were identified. Cluster 1 (C1; n=24/88) included dyslipidemia, hypertension and early-onset gout without tophi. Cluster 2 (C2; n=25/88) included hypertension, dyslipidemia, nephrolithiasis, and obesity. Cluster 3 (C3; n=39/88) included all comorbidities and tophi.

Our findings provide novel insights into, and expand our understanding of, the pathogenesis of gout and gout-associated comorbidities.

The mean serum urate levels of C2 were higher than those of C1 and C3 (7.74 vs 6.83 and 5.67 mg/dL, respectively). Patients in C1 vs C2 and C3 had higher levels of inflammatory markers (3-nitrotyrosine oxyHb, total heme, C-reactive protein [CRP], tumor necrosis factor [TNF], interleukin [IL]-1B, platelet-derived growth factor [PDGF]-AA and PDGF-BB). However, patients in C2 vs C1 and C3 had higher levels of hemolysis and oxidative stress markers, suggestive of a connection to kidney impairment and multiple comorbidities. Patients in C3 vs C1 and C2 had higher inflammatory cytokines (carbonyl, nitrite, 8-isoprostane, IL-6, CCL2/MCP).

When reclustering for 6 biological markers (3 oxidative stress markers and 3 inflammatory cytokines), significant differences were noted compared with the initial 3 clusters (C*1, C*2, C*3). Patients in C*3 were found to be older at the time of diagnosis than those in C*1 and C2 (52.40 vs 46.23 and 48.33 years, respectively). Patients in C*2 had a higher mean serum creatinine (1.82 mg/dL) than that among patients in the other 2 clusters. 

Reclustering of patients with gout based on all biological markers also led to significantly different clusters compared with the initial 2 clusters (C**1, C**2, C**3). Compared with patients in C**2 and C**3, those in C**1 were at a younger age at the time of diagnosis. Patients in C**3 vs C**1 and C**2 were found to be primarily of African American descent and younger at enrollment (60.33 vs 61.56 and 62.56 years, respectively).

Notably, patient clusters contingent on disease severity/onset and comorbidities differed by inflammatory and oxidative stress markers. Systemic oxidative stress was shown to be prominent in patients with gout with hyperuricemia, chronic kidney disease, coronary artery disease, or cerebrovascular disease. 

Study limitations included the cross-sectional design; lack of data from a control group; and the inability to adjust for multiple comparisons. 

The study authors concluded, “…mitigating oxidative stress and inflammatory cytokine levels could be a valuable adjunctive strategy for the effective management of difficult-to-treat gout.” They added, “Our findings provide novel insights into, and expand our understanding of, the pathogenesis of gout and gout-associated comorbidities.”


Alduraibi FK, Saleem M, Ricart K, Patel RP, Szalai AJ, Singh JA. Clustering patients with gout based on comorbidities and biomarkers: a cross-sectional study. J Rheum. Published online February 1, 2023. doi:10.3899/jrheum.220635