Association Between Time-Averaged Serum Uric Acid and Renal Outcomes in Patients with Type 2 Diabetes Mellitus with Chronic Kidney Disease: A Multicenter Retrospective Cohort Study

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The aim of this work is to explore the association of time-averaged serum uric acid (TA-SUA) with renal outcomes of type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). A cohort of T2DM with CKD from eight centers was followed from January 2013 to January 2023. A Cox proportional hazards regression model was designed to evaluate the association of TA-SUA with renal outcomes (defined as serum creatinine doubling, or initiation of dialysis, or kidney transplantation, or progression to end-stage kidney disease). Cox proportional hazards regression with cubic spline functions and smooth curve fitting were used to explore the nonlinear relationship. Detailed evaluations for TA-SUA were also performed using propensity score matching (PSM), subgroup analyses, and sensitivity analyses. A total of 1072 patients were enrolled with a mean follow-up duration of 60.4 ± 5.6 months. The baseline prevalence of hyperuricemia was 46.1% (50.4% in male vs. 37.9% in female). Patients with TA-SUA < 360 μmol/l demonstrated significantly better renal survival compared to those with TA-SUA ≥ 360 μmol/l (adjusted hazard ratio 0.63, 95% confidence interval, 0.41–0.98; P = 0.038). Restriction cubic spline analysis showed a rapid risk increase when TA-SUA exceeded 360 μmol/l, which was confirmed by PSM (P < 0.001). Subgroup analyses and sensitivity analyses showed that patients with eGFR between 30 and 59 ml/min/1.73 m 2 were the most likely to benefit from maintaining TA-SUA < 360 μmol/l. Long-term maintenance of relatively low TA-SUA levels is independently associated with slowed renal function decline and favorable renal outcomes among patients with type 2 DM with CKD.

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