Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease （DKD） in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis， and to explore its mechanism of inhibiting the endoplasmic reticulum stress （ERS）-apoptosis axis and delaying renal fibrosis （RF）. MethodsA single-center， randomized， parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine （TCM） pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group （conventional Western medicine treatment） and an experimental group （Yishen Jiangtang decoction combined with conventional Western medicine treatment）， with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters： Blood urea nitrogen （BUN）， serum creatinine （SCr）， estimated glomerular filtration rate （eGFR）， urinary albumin-to-creatinine ratio （UACR）， fasting blood glucose （FBG）， triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C）. Enzyme-linked immunosorbent assay （ELISA） kits were used to measure serum glucose-regulated protein 78 （GRP78）， serum cysteinyl aspartate-specific protease-3 （Caspase-3）， and serum and urinary transforming growth factor-β₁ （TGF-β₁） levels before and after treatment. TCM symptom scores， TCM syndrome efficacy， and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3， as well as serum and urinary levels of TGF-β1， with renal function， proteinuria， and glucose and lipid metabolism indicators in patients with DKD. In addition， safety indicators were also monitored. ResultsA total of 75 patients completed the study （38 in the control group and 37 in the experimental group）. ① Baseline data： The two groups were comparable in terms of sex and age， with no statistically significant difference. ② Efficacy outcomes： Compared with baseline levels， both groups showed reductions in BUN， SCr， UACR， FBG， TG， TC， LDL-C， and TCM symptom scores （P<0.01） and increases in eGFR level （P<0.01）. Moreover， the experimental group outperformed the control group in altering the indicators above （P<0.05）. Regarding TCM syndrome efficacy， the total response rate in the experimental group was 83.78%， which was higher than that （57.89%） in the control group （P<0.05）. Regarding overall clinical efficacy， the total response rate in the experimental group was 78.38%， which was higher than that （50.00%） in the control group （P<0.05）. ③ Mechanism outcomes： Compared with baseline levels， both groups showed declined serum levels of GRP78， Caspase-3， and TGF-β₁ and urinary level of TGF-β₁ after treatment （P<0.01）. Moreover， the experimental group showed greater declines than the control group （P<0.05）. The serum levels of GRP78， Caspase-3，and TGF-β₁ and the urinary level of TGF-β₁ in DKD patients showed positive correlations with BUN， SCr， UACR， and FBG and negative correlations with eGFR （P<0.05）. ④ Safety outcomes： Neither group showed drug-related adverse reactions， and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms， correct glucose and lipid metabolism disorders， and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.

ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease （DKD） in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis， and to explore its mechanism of inhibiting the endoplasmic reticulum stress （ERS）-apoptosis axis and delaying renal fibrosis （RF）. MethodsA single-center， randomized， parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine （TCM） pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group （conventional Western medicine treatment） and an experimental group （Yishen Jiangtang decoction combined with conventional Western medicine treatment）， with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters： Blood urea nitrogen （BUN）， serum creatinine （SCr）， estimated glomerular filtration rate （eGFR）， urinary albumin-to-creatinine ratio （UACR）， fasting blood glucose （FBG）， triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C）. Enzyme-linked immunosorbent assay （ELISA） kits were used to measure serum glucose-regulated protein 78 （GRP78）， serum cysteinyl aspartate-specific protease-3 （Caspase-3）， and serum and urinary transforming growth factor-β₁ （TGF-β₁） levels before and after treatment. TCM symptom scores， TCM syndrome efficacy， and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3， as well as serum and urinary levels of TGF-β1， with renal function， proteinuria， and glucose and lipid metabolism indicators in patients with DKD. In addition， safety indicators were also monitored. ResultsA total of 75 patients completed the study （38 in the control group and 37 in the experimental group）. ① Baseline data： The two groups were comparable in terms of sex and age， with no statistically significant difference. ② Efficacy outcomes： Compared with baseline levels， both groups showed reductions in BUN， SCr， UACR， FBG， TG， TC， LDL-C， and TCM symptom scores （P<0.01） and increases in eGFR level （P<0.01）. Moreover， the experimental group outperformed the control group in altering the indicators above （P<0.05）. Regarding TCM syndrome efficacy， the total response rate in the experimental group was 83.78%， which was higher than that （57.89%） in the control group （P<0.05）. Regarding overall clinical efficacy， the total response rate in the experimental group was 78.38%， which was higher than that （50.00%） in the control group （P<0.05）. ③ Mechanism outcomes： Compared with baseline levels， both groups showed declined serum levels of GRP78， Caspase-3， and TGF-β₁ and urinary level of TGF-β₁ after treatment （P<0.01）. Moreover， the experimental group showed greater declines than the control group （P<0.05）. The serum levels of GRP78， Caspase-3，and TGF-β₁ and the urinary level of TGF-β₁ in DKD patients showed positive correlations with BUN， SCr， UACR， and FBG and negative correlations with eGFR （P<0.05）. ④ Safety outcomes： Neither group showed drug-related adverse reactions， and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms， correct glucose and lipid metabolism disorders， and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.