Effects of Empagliflozin on Uric Acid and Gout in CKD

Kaitlin J. Mayne and colleagues conducted exploratory analyses of data from the EMPA-KIDNEY trial to determine the effects of sodium-glucose co-transporter-2 (SGLT2) inhibition on uric acid and gout in patients with chronic kidney disease (CKD). EMPA-KIDNEY comprised 6,609 patients with CKD (eGFR ≥20 and <90 mL/min/1.73m2) who were randomized to receive empagliflozin 10 mg daily or placebo over a median of two years of follow-up.  

The researchers measured serum uric acid at randomization, at two months, and at 18 months. They used a prespecified mixed model repeated measures approach to evaluate the effects of empagliflozin and analyzed patient-reported gout events in Cox regression models (first events) with the Andersen-Gill extension (total events). EMPA-KIDNEY primary and kidney disease progression outcomes were assessed in subgroups of baseline serum uric acid, and a post-hoc composite outcome included new initiation of uric acid lowering therapy or colchicine.  

Mean serum uric acid concentration was 431±114 µmol/L at baseline. Randomization to the empagliflozin group resulted in a serum uric acid between-group difference of -25.6 (95% CI, -30.3 to -21.0) µmol/L. Larger effects were observed in participants with higher eGFR (trend P<.001) and without diabetes (heterogeneity P<.001).  

Empagliflozin did not significantly reduce first or total gout events compared to placebo (HR, 0.87; 95% CI, 0.74-1.02 for the 595 first events, and 0.86, 0.72-1.03 for the 869 total events). Hazard ratios were similar for the post-hoc composite and across subgroups, including diabetes and eGFR. The effects of empagliflozin on the primary outcome and kidney disease progression outcomes were similar regardless of baseline uric acid level. 

In conclusion, the authors said, “SGLT2 inhibition reduces serum uric acid in patients with CKD with larger effects at higher eGFR and in the absence of diabetes. However, the effect on uric acid is modest and did not translate into reduced risk of gout in EMPA-KIDNEY.” 

Source: Nephrology Dialysis Transplantation.