TOPLINE:

An analysis of two large, geographically independent gout cohorts revealed distinctly unique clinical and genetic features linked with different subtypes of hyperuricemia, indicating discrete pathophysiologic pathways for each subtype.

METHODOLOGY:

• Hyperuricemia, a universal condition in patients with gout, can be classified into four subtypes on the basis of the urinary uric acid excretion values; however, the unique biologic traits of each subtype have not yet been thoroughly investigated.
• This cross-sectional study conducted at two centers in North and South China aimed to understand the clinical and genetic characteristics of different hyperuricemia subtypes in 4873 patients (mean age, 44.4 years; 2.3% women) with gout.
• The hyperuricemia subtypes were defined as renal uric acid overload (ROL), renal underexcretion (RUE), combined, or renal normal subtypes on the basis of both 24-hour urinary uric acid excretion and uric acid fractional excretion values.
• Polygenic risk scores were calculated for 1240 randomly chosen patients who were genotyped for 20 distinct single nucleotide polymorphisms linked to the risk for gout.
• Before collecting laboratory samples, all participants followed a low purine diet (purine intake < 200 mg/d) and underwent a 14-day washout period during which they were instructed to stop taking any medication that may lower urate levels.
• RUE was the most prevalent subtype (60.9%), followed by combined (23.1%), ROL (8.8%), and the normal subtype (7.2%).
• The clinical predictors associated with each hyperuricemia subtype were:
  • Older age at onset, lower serum urate levels, a higher amount of sodium urate crystals in the synovial fluid, and the presence of diabetes indicated ROL.
  • A lower body mass index (BMI) and absence of diabetes indicated RUE.
  • Younger age at onset, higher BMI, higher serum urate levels, more smoking, and a less advanced stage of chronic kidney disease (CKD) indicated the combined subtype.
  • Older age, lower serum urate levels, more nephrolithiasis, and a more advanced CKD stage indicated the renal normal subtype.
• High vs low polygenic risk scores were correlated with ROL (odds ratio [OR], 9.63; 95% CI, 4.53-15.12), RUE (OR, 2.18; 95% CI, 1.57-3.03), and the combined subtype (OR, 6.32; 95% CI, 4.22-9.48).

IN PRACTICE:

“These results might enable the development of clinical and/or genetic variable-based risk model for specific subtypes and, even further, of subtype-dependent genetic-based therapies for gout/hyperuricemia,” the authors added.

SOURCE:

This study was led by Han Qi, Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, China, and published online on February 27 in Arthritis & Rheumatology.

LIMITATIONS:

Owing to the cross-sectional nature of this study, conclusions regarding responses to urate-lowering medications or disease prognosis could not be drawn. Patients experiencing frequent gout flares and other conditions before and during the washout period were not included in this analysis. Finally, the study was conducted by including solely Chinese patients with gout, limiting the generalizability of the study findings.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, Projects of International Cooperation and Exchanges NSFC, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.