Traditional Chinese Medicine for Diabetic Kidney Disease: Predominantly Preclinical Evidence, Mechanistic Pathways, and Translational Challenges.

Diabetic kidney disease (DKD) is a type of kidney microvascular complication resulting from diabetes, and it is one of the leading causes of end-stage kidney disease (ESKD). Existing drugs improve kidney function but do not markedly delay progression to ESKD or reduce mortality, so complementary approaches are urgently needed. This paper summarizes the evidence for traditional Chinese medicine (TCM) in DKD, organized by pathological mechanism. The studies identified here were almost exclusively preclinical, based on rodent models of DKD and on kidney cells exposed to high glucose. Across these studies, TCM interventions improved kidney function indices and attenuated glomerular and tubulointerstitial injury. The evidence is unevenly developed and was graded accordingly. Attenuation of oxidative stress, inflammation and kidney fibrosis is the best supported, whereas the modulation of autophagy, ferroptosis and the gut microbiota rests on a smaller number of studies. Podocyte injury, pyroptosis, apoptosis and mitochondrial dysfunction are each supported by only a few reports, and all of these mechanisms remain exploratory. Reported effects included restored antioxidant enzyme activity, reduced pro-inflammatory cytokine production, suppressed profibrotic signaling, increased levels of autophagy-related proteins, preserved glutathione peroxidase 4, reduced abundance of uremic toxin-producing gut taxa and preserved podocyte markers. Only a few agents have entered controlled trials, and some support comes from population-based cohorts, which report lower risks of ESKD and all-cause mortality among TCM users. Because reported outcomes are largely surrogate endpoints, TCM may currently be positioned only as a complementary or adjunctive therapy, pending confirmation in large multicenter randomized trials with hard kidney outcomes.