[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Met...[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Methods]Retrospective analysis was made on 30 patients with DKD who were diagnosed with damp-heat stasis syndrome in the clinical proteinuria stage from March 2021 to March 2023 in Jiangsu Province Hospital of Chinese Medicine,and who took Kunkui Kidney Preserving Paste continuously for six months.The urinary albumin/creatinine ratio(UACR),urinary complement C3,and urea nitrogen(BUN)of DKD patients before and after treatment were compared,and estimated glomerular filtration rate(eGFR),blood creatinine(Scr),and cystatin C(CysC)were estimated,and the therapeutic effects on renal function and urinary protein were evaluated.[Results]After treatment,UACR significantly decreased(P<0.01),and urinary complement C3 and Scr decreased(P<0.05),while other indicators showed no significant statistical difference(P>0.05).In terms of evaluating the efficacy of urinary protein therapy,8 cases showed recent relief;8 cases showed significant effect;9 cases were effective,and 5 cases were invalid after treatment,with a total effective rate of 83.33%.In terms of renal function efficacy evaluation,8 cases showed significant effect;4 cases were effective;11 cases were stable,and 7 cases were invalid,with a total effective rate of 76.67%.In the safety evaluation,there were no obvious adverse reactions.[Conclusions]The Kunkui Kidney Preserving Past has significant clinical efficacy and safety in treating DKD patients with damp-heat stasis syndrome in the clinical proteinuria period.It has significant advantages in reducing urinary protein and protecting renal function,which is worthy of clinical promotion.展开更多
BACKGROUND Diabetic kidney disease(DKD)stands as the key contributor to chronic kidney disease worldwide.Clinical studies have shown that Kunkui Baoshen decoction(KKBS)effectively reduces proteinuria and enhances rena...BACKGROUND Diabetic kidney disease(DKD)stands as the key contributor to chronic kidney disease worldwide.Clinical studies have shown that Kunkui Baoshen decoction(KKBS)effectively reduces proteinuria and enhances renal function in DKD patients.However,its precise molecular targets and therapeutic mechanisms remain to be thoroughly clarified.AIM To evaluate the nephroprotective efficacy of KKBS in DKD and explore the underlying mechanisms of action.METHODS Liquid chromatography-tandem mass spectrometry was utilized to analyze the chemical constituents of KKBS.Metabonomic and transcriptomic analyses were conducted to identify key targets and pathways associated with the therapeutic effects of KKBS on DKD.The nephroprotective effects of KKBS were assessed both in high glucose-induced human kidney-2 cells and in db/db mice.A variety of assays were performed,including Cell Counting Kit-8,Western blot,quantitative reverse transcription-polymerase chain reaction,immunofluorescence,coimmunoprecipitation,periodic acid-Schiff staining,Masson staining,hematoxylin and eosin staining,immunohistochemistry,and mitochondrial morphology analysis.RESULTS The glutathione metabolic pathway emerged as the most prominent metabolic pathway in the metabonomic analysis of KKBS.Transcriptomic and bioinformatic analyses revealed that nuclear receptor coactivator 4(NCOA4)was instrumental in regulating ferroptosis within renal tubules of mice with DKD.Both in vitro and in vivo experiments showed that KKBS ameliorated renal dysfunction,mitigated renal tissue damage,and repressed the expression of autophagy-dependent ferroptosis markers and inflammatory fibrosis.Mechanistically,KKBS enhanced the interaction between the homologous to E6-AP C-terminus and RCC1-like domaincontaining E3 ubiquitin protein ligase(HERC2)and NCOA4,leading to K48-related ubiquitination and subsequent degradation of NCOA4.This process inhibited autophagy-dependent ferroptosis,reduced the release of pro-fibrotic inflammatory factors,and ultimately exerted an anti-fibrotic effect in DKD.CONCLUSION KKBS confers nephroprotection in DKD by modulating HERC2/NCOA4-mediated autophagy-dependent ferroptosis,thereby alleviating renal fibrosis.展开更多
基金Supported by the National Natural Science Foundation of China(82174293,82374355,82004286)Science and Technology Support Program of Jiangsu Province(ZD202208,ZT202206)Postgraduate Research and Practice Innovation Program of Jiangsu Province(SJCX22_0718).
文摘[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Methods]Retrospective analysis was made on 30 patients with DKD who were diagnosed with damp-heat stasis syndrome in the clinical proteinuria stage from March 2021 to March 2023 in Jiangsu Province Hospital of Chinese Medicine,and who took Kunkui Kidney Preserving Paste continuously for six months.The urinary albumin/creatinine ratio(UACR),urinary complement C3,and urea nitrogen(BUN)of DKD patients before and after treatment were compared,and estimated glomerular filtration rate(eGFR),blood creatinine(Scr),and cystatin C(CysC)were estimated,and the therapeutic effects on renal function and urinary protein were evaluated.[Results]After treatment,UACR significantly decreased(P<0.01),and urinary complement C3 and Scr decreased(P<0.05),while other indicators showed no significant statistical difference(P>0.05).In terms of evaluating the efficacy of urinary protein therapy,8 cases showed recent relief;8 cases showed significant effect;9 cases were effective,and 5 cases were invalid after treatment,with a total effective rate of 83.33%.In terms of renal function efficacy evaluation,8 cases showed significant effect;4 cases were effective;11 cases were stable,and 7 cases were invalid,with a total effective rate of 76.67%.In the safety evaluation,there were no obvious adverse reactions.[Conclusions]The Kunkui Kidney Preserving Past has significant clinical efficacy and safety in treating DKD patients with damp-heat stasis syndrome in the clinical proteinuria period.It has significant advantages in reducing urinary protein and protecting renal function,which is worthy of clinical promotion.
基金Supported by National Natural Science Foundation of China,No.82205025,No.82374355,and No.82174293.
文摘BACKGROUND Diabetic kidney disease(DKD)stands as the key contributor to chronic kidney disease worldwide.Clinical studies have shown that Kunkui Baoshen decoction(KKBS)effectively reduces proteinuria and enhances renal function in DKD patients.However,its precise molecular targets and therapeutic mechanisms remain to be thoroughly clarified.AIM To evaluate the nephroprotective efficacy of KKBS in DKD and explore the underlying mechanisms of action.METHODS Liquid chromatography-tandem mass spectrometry was utilized to analyze the chemical constituents of KKBS.Metabonomic and transcriptomic analyses were conducted to identify key targets and pathways associated with the therapeutic effects of KKBS on DKD.The nephroprotective effects of KKBS were assessed both in high glucose-induced human kidney-2 cells and in db/db mice.A variety of assays were performed,including Cell Counting Kit-8,Western blot,quantitative reverse transcription-polymerase chain reaction,immunofluorescence,coimmunoprecipitation,periodic acid-Schiff staining,Masson staining,hematoxylin and eosin staining,immunohistochemistry,and mitochondrial morphology analysis.RESULTS The glutathione metabolic pathway emerged as the most prominent metabolic pathway in the metabonomic analysis of KKBS.Transcriptomic and bioinformatic analyses revealed that nuclear receptor coactivator 4(NCOA4)was instrumental in regulating ferroptosis within renal tubules of mice with DKD.Both in vitro and in vivo experiments showed that KKBS ameliorated renal dysfunction,mitigated renal tissue damage,and repressed the expression of autophagy-dependent ferroptosis markers and inflammatory fibrosis.Mechanistically,KKBS enhanced the interaction between the homologous to E6-AP C-terminus and RCC1-like domaincontaining E3 ubiquitin protein ligase(HERC2)and NCOA4,leading to K48-related ubiquitination and subsequent degradation of NCOA4.This process inhibited autophagy-dependent ferroptosis,reduced the release of pro-fibrotic inflammatory factors,and ultimately exerted an anti-fibrotic effect in DKD.CONCLUSION KKBS confers nephroprotection in DKD by modulating HERC2/NCOA4-mediated autophagy-dependent ferroptosis,thereby alleviating renal fibrosis.
