Randomized Controlled Clinical Trial of Shenzhuo Formula in the Treatment of Macroalbuminuria in Diabetic Kidney Disease and Its Inflammation-Modulating Mechanisms
Precision Clinical Medicine, 2025
Anzhu W., Yishan H., Yu W., Lili Z., hongdong C., Xiaoqing W., Zhimei C., Bin W., Wei L., Chao C., Ye L., Zhonghua Z., Yan W., Jia M., Keda L., Ying Z., Xiaolin T., Linhua Z.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases Nephrology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
Shenzhuo Formula (SZF), a modified Didang Tang, is used for diabetic kidney disease (DKD), though high-quality evidence is limited.
Methods
In a randomized, double-blind, double-dummy, active-controlled, multicenter trial, irbesartan was the control. A Bayesian model assessed efficacy. Mechanistic studies included Olink inflammation proteomics, single-cell RNA sequencing (scRNA-seq) of KK-Ay mouse kidneys, and in vivo experiments.
Results
120 DKD patients with macroalbuminuria were randomized (SZF n = 57, irbesartan n = 63). At 24 weeks, 24hUTP change was −0.03 (−0.24 to 0.18) g/24h in the SZF group and 0.08 (−0.30 to 0.14) g/24h in the irbesartan group (P = 0.61). eGFR improved with SZF by 5.91 (1.80 to 10.01) mL/min/1.73m² but declined with irbesartan by −1.67 (−5.18 to 1.84) mL/min/1.73m² (P < 0.01). SCr decreased with SZF by −5.15 (−9.73 to −0.56) μmol/L but increased with irbesartan by 3.39 (−0.84 to 7.61) μmol/L (P < 0.01). TCM syndrome response was higher with SZF (89.47% vs. 63.49%, P < 0.01). Safety and metabolic parameters were comparable. Bayesian analysis favored SZF for renal benefit. Mechanistically, SZF downregulated CX3CL1 in endothelial cells and MCP-1 in mesangial and tubular cells, suggesting anti-inflammatory effects restoring endothelial function and attenuating fibrosis.
Conclusions
SZF matched irbesartan in proteinuria reduction but was superior in preserving renal function and improving TCM symptoms in DKD, with good safety. Benefits may involve suppression of CX3CL1/MCP-1–mediated inflammation.