Exploratory Mediation-Informed Analysis and Dose-Response Analysis of Uric Acid Reduction and Kidney Outcomes in SGLT2 Inhibitor Therapy Compared to Allopurinol
Abstract
Background: Hyperuricemia has long been linked to the progression of chronic kidney disease (CKD), although the role of serum uric acid (sUA) reduction in kidney preservation remains uncertain. Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower sUA levels and exert renoprotective effects, but it is unclear whether these findings are mechanistically related. Methods: Adult patients with type 2 diabetes mellitus and hyperuricemia were included from a retrospective cohort. Patients treated with empagliflozin (n = 70) or dapagliflozin (n = 78) were pooled into a single group and compared with an allopurinol-treated group (n = 66). Exploratory mediation-informed analysis models assessed associations between treatment, changes in sUA (ΔsUA), and changes in estimated glomerular filtration rate (ΔeGFR) at 12 and 36 months. Dose-response and nonlinear associations between ΔsUA and ΔeGFR were additionally examined. Results: At 12 months, SGLT2 inhibitor treatment was associated with greater ΔsUA compared with allopurinol (B = 22.62, p = 0.040); its direct association with ΔeGFR remained significant after adjustment for ΔsUA (B = -6.14, p < 0.001). At 36 months, the association of treatment with ΔsUA was no longer significant, whereas association with ΔeGFR persisted (B = -11.8, p < 0.001). No dose-response or nonlinear relationship was identified between ΔsUA and ΔeGFR, while treatment remained an independent predictor of ΔeGFR at both time points. Conclusions: Reductions in sUA…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 78 participants or records.
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