Background: Gout is a frequent comorbidity in kidney transplant (KT) recipients. However, assessing the independent effect of gout on KT outcomes is difficult because of multiple confounders (e.g., temporal changes in estimated glomerular filtration rate [eGFR], cyclosporine or tacrolimus dose, urate-lowering medication use) that obscure a clear picture of gout’s potential impact.
Objectives: This investigation assessed if the development of new-onset gout after KT was an independent risk factor for loss of graft function, as assessed by the need for maintenance hemodialysis following KT.
Methods: This retrospective cohort study analyzed data on patients in the United States Renal Data System (USRDS) who received a primary KT between 1/1/2008 and 12/31/2015. The date of transplantation was the ‘index’ date. Eligible patients were required to have ≥24 months of Medicare coverage and no prior history of gout, defined as ≥1 claim with a gout diagnosis code in the 24 months prior to the index date. All patients were also required to have ≥12 months of coverage post index. Patients who died, experienced graft failure, or returned to dialysis <12 months post index were excluded. Because the first year following transplant is associated with the highest frequency of rejections, we evaluated subjects beginning 1 year after transplant. The exposure of interest was new-onset gout, defined as the presence of ≥2 claims for gout post index, and the primary endpoint was return to dialysis >12 months post index. Baseline time-invariant confounders included recipient and donor demographics and clinical characteristics at index. Time-varying confounders included body mass index (BMI) adjusted tacrolimus and cyclosporine dose, eGFR, and urate-lowering medication use post index. Patients who died or lost Medicare coverage >12 months post index were censored; all patients remaining at the end of the study period (12/31/2016) were also censored. A marginal structural model (MSM) was fitted to determine the relative risk of new-onset gout on return to dialysis, while controlling for both time-invariant and time-varying confounders.
Results: 18,525 of 466,589 KT recipients in the USRDS met study eligibility. Within the observation period, 1,399 (7.6%) developed new-onset gout and 1,420 (7.7%) returned to dialysis >12 months post index. Median time from index to new-onset gout and from index to return to dialysis was 16.2 months (IQR: 33.4) and 32.8 months (IQR: 28.4), respectively. Adjusting for baseline time-invariant and time-varying confounders via the MSM showed new-onset gout was associated with a 51% increased risk of return to dialysis >12 months post index (RR: 1.51, 95% CI: 1.03, 2.20).
Conclusion: New-onset gout was independently associated with a 51% increased risk of return to dialysis >12 months after primary KT compared to a control cohort without gout. To our knowledge, this is the first observation of this outcome in an appropriately controlled cohort study of KT recipients with gout. Results from this analysis may have important implications for the monitoring and management of new-onset gout in the kidney transplant population.
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Disclosure of Interests: : Justin Li: None declared, David Yin: None declared, Zheng Wang: None declared, Mark Brigham: None declared, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Jeffrey Kent Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Richard Johnson Shareholder of: Colorado Research Partners LLC, XORTX Therapeutics, Consultant of: Horizon Therapeutics, Eli Lilly, Speakers bureau: Horizon Therapeutics, Nandini Hadker: None declared, Kevin Francis: None declared, Herman Sanchez: None declared, Gavin Miyasato: None declared
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