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  1. N. McCormick1,2,3,4,
  2. L. Lu4,
  3. C. Yokose1,2,3,
  4. A. Joshi2,3,5,
  5. Y. Zhang1,2,3,
  6. H. Choi1,2,3,4
  1. 1Massachusetts General Hospital, Rheumatology, Allergy, and Immunology, Boston, United States of America
  2. 2The Mongan Institute, Medicine, Boston, United States of America
  3. 3Harvard Medical School, Medicine, Boston, United States of America
  4. 4Arthritis Research Canada, -, Vancouver, Canada
  5. 5MGH Clinical and Translational Epidemiology Unit, Medicine, Boston, United States of America


Background Serum urate (SU) is a necessary causal factor for development of gout, while chronic kidney disease (CKD) is associated with increased inflammatory biomarkers, cytokines, and reduced AMPK activity levels. Furthermore, CKD has been found to be associated with an increased risk of incident gout, even beyond (i.e., independent of) SU levels. As such, the impact of SU may be enhanced by presence of CKD, but this hypothesis has not been evaluated.

Objectives To prospectively examine whether CKD modifies the relation between SU levels and risk of incident gout.

Methods We conducted a prospective cohort analysis of UK Biobank participants with urate and creatinine levels available from baseline blood samples (2006-2010), and no prior diagnosis of gout or urate lowering therapy use. CKD Stage ≥ 3 status (eGFR <60 mL/min) was determined from latest CKD-Epi equations (NEJM 2021; JASN 2021).1,2 Incident cases of gout were ascertained from linked hospitalisation, primary care, and death records. Participants were followed from baseline up to 10 years or until gout diagnosis, death, or end of study period (Dec 31/19).

We calculated 10-year cumulative incidence of gout according to baseline SU category and CKD status and evaluated their individual and joint impact on gout risk using multivariable Cox proportional hazards models.

We further assessed for additive and multiplicative interactions3 between levels of SU and inverted eGFR, on a standardized continuous scale per SD.

Results We included 458,244 individuals (45% male, mean age 56.5 years), of whom 6,559 had CKD at baseline, and documented 5,847 cases of incident gout over 4,442,866 person-years.

10-year cumulative incidence of gout ranged from 0.2% (baseline SU < 5 mg/dL) to 33% (baseline SU ≥ 10 mg/dL), and in each category incidence was higher for those with CKD than without (Table 1; Figure 1-left), Multivariable hazard ratio (HR) for the joint effect of CKD and highest SU level (≥ 10 mg/dL), compared to non-CKD and lowest SU (<5mg/dL), was 242 (95% CI: 189 to 309) (Figure 1-right).

Table 1.

Cumulative incidence and hazard ratio (HR) of incident gout according to baseline serum urate levels and CKD status

There was a significant additive interaction between continuous SU and eGFR (relative excess risk due to interaction=0.16 [0.09 to 0.24], p < 0.001), with HRs of 3.7 (3.6 to 3.8) per SD increase of SU, 1.2 (1.2 to 1.3) per SD increase of inverted eGFR, and 4.1 (3.9 to 4.2) for their joint effect. Their multiplicative interaction was also significant (p < 0.001).

Conclusion These large prospective cohort data suggest CKD presence enhances the effect of elevated SU levels on risk of incident gout. They support roles of CKD-associated factors beyond SU in developing gout, such as reduced AMPK activity levels and altered inflammatory factors in CKD, which warrant further investigation.

References [1]PMID 34554658

[2]PMID 34556489

[3]ARD (2021) PMID 34857519

Disclosure of Interests Natalie McCormick: None declared, Leo Lu: None declared, Chio Yokose: None declared, Amit Joshi: None declared, Yuqing Zhang: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart., Grant/research support from: Ironwood and Horizon

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