Abstract: Objective:To investigate the relationship between longitudinal serum uric acid (SUA) trajectories and the progression and prognosis of kidney injury in patients with stage Ⅲ diabetic kidney disease (DKD). Methods:This study enrolled 250 patients with biopsy-proven stage Ⅲ DKD,with a median follow-up of 4.2 years.Group-based trajectory modeling applied to serial SUA measurements was used to identify three distinct trajectory groups:a low-trajectory group [5.2 (4.6,5.7) mg/dl,n=70], a moderate-trajetory group [6.4 (5.9,7.1) mg/dl,n=125], and a high-trajectory group [7.7 (6.8,9.1) mg/dL,n=55]. The association between SUA trajectory groups and the rate of estimated glomerular filtration rate (eGFR) decline was assessed using generalized linear mixed-effects models.The composite kidney outcome was defined as a≥50% decline in eGFR,progression to end-stage kidney disease (ESKD),or initiation of kidney replacement therapy.Kaplan-Meier survival analysis and Cox proportional hazards models were employed to analyze the association between SUA trajectory groups and the kidney outcome. Results:During follow-up,for each 1mg/dL increase in SUA,on top of the annual rate of eGFR decline,the low,moderate,and high trajectory groups showed additional changes of -0.65%(95% CI-1.25%~-0.03%,P=0.04),0.45%(95% CI 0.03%~0.87%,P=0.04),and -1.03%(95% CI-1.67%~-0.38%,P<0.01), respectively. A total of 192 patients (76.8%) experienced the composite kidney outcome.In the multivariable-adjusted Cox model,compared to the low-trajectory group,the hazard ratios (HRs) for the moderate- and high-trajectory groups were 1.291 (95% CI 0.88~1.90,P=0.20) and 1.604 (95% CI 1.01~2.54,P=0.043).Conclusion: This study found that the effect of SUA on the rate of eGFR decline exhibited a U-shaped distribution across different trajectory groups.Furthermore,maintaining a high SUA level over the long term is an independent risk factor for progression to the composite kidney outcome.

Key words: stage Ⅲ diabetic kidney disease,serum uric acid,trajectory analysis,renal function decline,estimated glomerular filtration rate