Trial evaluates a traditional Chinese herbal formula for diabetic kidney disease with macroalbuminuria

Diabetic kidney disease affects a growing proportion of people with diabetes and remains the leading cause of end-stage renal disease. Clinically, the condition is marked by persistent proteinuria and a gradual decline in kidney filtration capacity. Current first-line therapies, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, typically slow renal function decline; however, sustained improvement is uncommon, and treatment-related adverse effects may limit long-term use. Increasing evidence suggests that chronic inflammation plays a central role in driving kidney fibrosis and functional loss in diabetes. Based on these challenges, there is a need to explore alternative or complementary treatments that can protect renal function by targeting inflammatory mechanisms.

Researchers from Guang'anmen Hospital of the China Academy of Chinese Medical Sciences, together with collaborators from multiple traditional Chinese medicine hospitals across China, reported (DOI: 10.1093/pcmedi/pbaf031) on November 14, 2025, in Precision Clinical Medicine the results of a multicenter, randomized, double-blind clinical trial evaluating a traditional Chinese herbal formula for diabetic kidney disease with macroalbuminuria. The 24-week study enrolled 120 patients and compared the therapy with the angiotensin receptor blocker irbesartan, assessing renal outcomes, safety, and symptom improvement. Mechanistic investigations combining proteomics, single-cell transcriptomics, and animal models were conducted to uncover inflammation-related pathways underlying the clinical effects.

The trial showed that both treatments achieved similar reductions in 24-hour urinary protein, a standard marker of kidney damage. However, patients receiving the herbal formulation experienced significantly better preservation of kidney function. Their estimated glomerular filtration rate increased over the treatment period, while it declined in the comparison group, and serum creatinine levels decreased rather than rising. Bayesian statistical analysis further supported a high probability that the herbal therapy provided meaningful renal benefits.

To understand why these differences occurred, the researchers conducted mechanistic studies. Olink inflammation proteomic profiling identified significant reductions in circulating inflammatory mediators, particularly CX3CL1 and MCP-1, following treatment. Single-nucleus RNA sequencing of diabetic mouse kidneys revealed that these molecules are predominantly expressed in endothelial, mesangial, and tubular cells—key players in kidney inflammation and fibrosis. Treatment suppressed their expression in specific cell populations, suggesting a cell-type-resolved anti-inflammatory effect.

Animal experiments reinforced these findings. Mice receiving the herbal therapy showed improved renal biochemical markers and reduced structural damage, including less fibrosis and mesangial expansion. Together, the clinical and experimental results indicate that the therapy may protect kidney function by dampening inflammation-driven injury rather than acting solely through hemodynamic control.

"The most striking aspect of this study is the improvement in kidney function, not just stabilization," said one of the corresponding investigators. "Many existing therapies slow decline, but few demonstrate an actual increase in filtration capacity. By integrating clinical trials with molecular and single-cell analyses, we were able to link these functional benefits to specific inflammatory pathways. This systems-level approach strengthens confidence that the observed effects are biologically meaningful and not simply statistical variation."

If confirmed in longer and larger trials, these findings could expand treatment options for patients with diabetic kidney disease, particularly those who cannot tolerate standard medications or remain at high residual risk. The study highlights inflammation as a viable therapeutic target and suggests that multi-component therapies may exert synergistic effects on complex disease pathways. Beyond this specific formulation, the work provides a framework for integrating traditional medicine with modern clinical trials and omics technologies. Such approaches could accelerate the discovery of complementary therapies aimed at preserving kidney function and improving quality of life for millions of patients worldwide.