Abstract:Objective To compare the clinical efficacy of Kunkui Baoshen Formula and Huangkui Capsules in patients with high or extremely high-risk diabetic kidney disease (DKD), and to explore the safety of their clinical application. Methods This study enrolled 314 high or extremely high-risk DKD patients from the Department of Endocrinology ofJiangsu Province Hospital of Chinese Medicine between February 2021 and August 2023. The patients were randomly divided into a control group and an experimental group (n=157, each). In addition to metabolic control, the control group received Huangkui Capsules (5 capsules per dose, 3 times a day, orally), while the experimental group received Kunkui Baoshen Formula. Both groups were treated for 3 months. Pre- and post-treatment, changes in urine protein- related indicators [urine albumin-to-creatinine ratio (UACR), urinary microalbumin (Um-Alb), urine retinol-binding protein (U-RBP), urine complement 3, urine α2-macroglobulin (MG) ], kidney function-related indicators [serum creatinine (Scr), cystatin C (Cys-C), estimated glomerular filtration rate (eGFR) ], and metabolic indicators [fasting blood glucose (FBG), glycated hemoglobin (HbA_1C), triglycerides (TG), systolic blood pressure, triglyceride-glucose (TyG) index]were observed. The clinical efficacy of proteinuria reduction, the recent reversal rate of proteinuria, kidney function efficacy, and changes in DKD clinical risk staging were also evaluated, and adverse reactions during treatment were recorded. Results Fourteen patients in the experimental group were lost to follow-up or excluded, and 143 patients completed the trial. Seventeen patients in the control group were lost to follow-up or excluded, and 140 patients completed the trial. After treatment, the UACR, Um-Alb, urine complement 3, and U-RBP in the experimental group significantly decreased compared to before treatment (P＜0.01), and urine α2-MG showed a downward trend. The reduction in UACR and Um-Alb was significantly superior to the control group (P＜0.01). The total clinical efficacy rate of proteinuria reduction was 83.22%, significantly better than 49.29% in the control group (χ²= 36.523, P＜0.01). The proportion of DKD patients with a reduction in UACR>30% reached 58.04%, which was significantly higher than 29.29% in the control group (χ²=23.763, P＜0.01). The decrease in serum creatinine and Cys -C, and the increase in eGFR in the experimental group were significantly better than those in the control group (P＜ 0.01), and the total effective rate of creatinine reduction was 67.83%, significantly better than 48.57% in the control group (χ²=10.795, P＜0.01). The FBG, TG, systolic blood pressure, and TyG index in the experimental group significantly decreased compared to before treatment (P＜0.05), with the reduction in TG, systolic blood pressure, and TyG index being superior to the control group (P＜0.05). Regarding changes in DKD clinical risk staging, the efficacy rate in the experimental group was higher than in the control group (36.36% vs 18.57%, χ²=11.217, P＜0.01). Both groups did not experience any severe adverse reactions during treatment, and there was no significant difference in the incidence of adverse reactions between the experimental group and control group (3.50% vs 1.43%, χ²=0.543, P= 0.461). Conclusion Kunkui Baoshen Formula has certain advantages over Huangkui Capsules in reducing proteinuria, protecting kidney function, improving related metabolic factors, and reversing DKD clinical risk staging. It demonstrates significant clinical efficacy and good safety.