Intensive Uric Acid-Lowering Improved Outcomes in Type 2 Diabetes with CKD: A Multicenter, Retrospective, Real-World Cohort Study

Background: To explorer the effects of intensive uric acid-lowering therapy on the outcomes in type 2 DM with chronic kidney disease (CKD). Methods: Patients diagnosed of type 2 DM with CKD( DKD) were enrolled in the nephrology department of 8 hospitals from January 2013. The patients were followed up to the end of the follow-up period (October 2023). Primary outcomes encompass a composite endpoint, including doubling of Scr, 40%-decline in eGFR, initiate dialysis, progression to end-stage renal disease or all-cause mortality. The risk factors and the relationship with prognosis were analyzed. To further explore the influence of baseline SUA (B-SUA) and time average SUA (TA-SUA) level fluctuation on the prognosis of DKD patients, logistic and Cox proportional risk regression models were used to analyze.For the HUA group (n=772) and NUA group (n=300),1:1 propensity score matching was used to clarify the optimal range of SUA and explore the benefit of intensive uric acid-lowering therapy to prevent and slow down the kidney damage. Results: 1651 patients were screened, 1072 patients with a median age of 56.5±10.4 years old, and 700 males (65.3%) were enrolled. The median of follow-up was 60.4±5.6 months. The overall prevalence of hyperuricemia incurrent cohort was 46.1%, which was higher in males than in females. The SUA level increased with age and was negatively correlated with renal function. After adjusting for confounding factors, we found that B-SUA and TA-SUA were independent risk factors for prognosis. In subgroup analysis, TA-SUA 360μmol/L was consistent among subgroups of age, sex, hemoglobin, glycosylated hemoglobin and lipid-lowering, glucose-lowering, blood-pressure lowering, and urico-lowering drug use.The spline curves demonstrated a U-shaped pattern after propensity score matching at B-SUA 360μmol/L and TA-SUA 300μmol/L respectively suggesting a potential threshold effect of SUA on prognostic risk. Conclusion: In this study, we found that hyperuricemia was an independent risk factor for outcomes. Intensive uric acid-lowering therapy especially maintaining SUA levels around 300~360μmol/L, delays end-point events in DKD.