Background/Purpose: Whether the presence of subclinical monosodium urate (MSU) crystal deposition leads to a pro-inflammatory state in asymptomatic hyperuricemia (AH) is unknown. We aimed to compare the inflammatory state in peripheral blood between AH patients with and without sonographic deposits.

Methods: Observational, cross-sectional study. Patients with current serum urate ≥7 mg/dl and no history of acute arthritis were consecutively recruited from internal medicine, cardiology, nephrology, endocrinology, rheumatology, and primary care. We excluded those on urate-lowering treatment or colchicine, another inflammatory rheumatic disease, or being under immunosuppressive therapy (including transplants).

Two comparative groups were predefined. Group 1: AH without deposits; and Group 2: AH with deposits. As sonographic deposits, we considered grade 2-3 double-contour sign and/or tophus according to 2021 OMERACT definitions¹, after a 10-location scanning (knees, tibiotalar joints, 1st and 2nd metatarsophalangeal joints, patellar and Achilles tendons) by a trained sonographer blinded to clinical and laboratory data. We measured serum levels of high-sensitivity C-reactive protein (hsCRP) in mg/dl (by immunoturbidimetry), serum amyloid-A in ng/ml (by nephelometry), and erythrocyte sedimentation rate (ESR) in mm/1h, as acute phase reactants. Later, using commercial ELISA kits, we analyzed: i) inflammasome NLRP3-related cytokines: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-18, IL-18 binding protein (IL-18BP); and ii) general pro-inflammatory and anti-inflammatory cytokines: tumor necrosis factor (TNF)-α, IL-6, soluble IL-6 receptor (sIL-6R), and transforming growth factor (TGF)-β.

GraphPad Prism (version 9.5.1) was used to compare AH groups, through Mann-Whitney U’s and Chi² tests.

Results: 77 subjects with AH were recruited, 71.4% men, with a mean age of 59.8 years (SD 17.3) and body mass index (BMI) of 31.2 kg/m² (SD 5.2). 37.7% and 29.9% had cardiovascular (CVD) and renal disease, respectively. Their mean uric acid was 7.6 mg/dl (SD 1.6).

Patients were classified into group 1 (n=35, 45.5%) or group 2 (n=42, 54.5%). There were no differences (group 2 vs. group 1) in age (67 vs. 56 years), men (69% vs.74.3%), BMI (31.7 vs. 29.9 kg/m²), CVD (38.1% vs. 37.1%), estimated glomerular filtration rate (73.42 vs. 75.03 ml/min/1.73m²), or current serum urate levels (7.35 vs. 7.40 mg/dl). The results of inflammatory markers and cytokines are presented in Figures 1 and 2. There were no differences between groups, but we observed numerical differences for hsCRP, IL-6, and TNF-α.

Conclusion: The inflammatory state was comparable in AH between those with and without sonographic deposits. Some hints were noted for hsCRP, IL-6, and TNF-α that further studies with larger sizes must confirm to establish the relevance of subclinical crystal deposition in AH.

Reference: [1] Christiansen SN. Semin Arthritis Rheum. 2021;51:644.

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/systemic-inflammation-associated-with-silent-deposition-of-monosodium-urate-crystals-in-asymptomatic-hyperuricemia/