scholarly journals Deciphering Chinese herbal medicine's efficacy and mechanisms for diabetic kidney disease: integrating web-based biochemical databases to the real-world clinical data (Preprint)

10.2196/27614 ◽  
2021 ◽  
Author(s):  
Chien-Wei Wu ◽  
Hsing-Yu Chen ◽  
Ching-Wei Yang ◽  
Yu-Chun Chen

2021 ◽  
Author(s):  
Chien-Wei Wu ◽  
Hsing-Yu Chen ◽  
Chin-Wei Yang ◽  
Yu-Chun Chen

BACKGROUND Diabetic kidney disease (DKD) is one of the most crucial causes of chronic kidney disease (CKD). However, the efficacy and biomedical mechanisms of using CHM for DKD in clinical settings remain unclear. OBJECTIVE This study aims to analyze the outcome of DKD patients with CHM-only management and the possible molecular pathways of CHM by integrating web-based biomedical databases and the real-world clinical database. METHODS A total of 152,357 patients with incident DKD from 2004 to 2012 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. The risk of mortality was estimated with the Kaplan–Meier method and Cox regression considering demographic covariates. The inverse probability of treatment weighting was used for confounding bias between CHM users and nonusers. Furthermore, to decipher the CHM used for DKD, we analyzed all CHM prescriptions using the Chinese herbal medicine network (CMN), which combined association rule mining and social network analysis among all CHM prescriptions. Further, web-based biomedical databases, including STITCH, STRING, BindingDB, TCMSP, TCM@Taiwan, DisGeNET, were integrated into the CMN and commonly used western medicine (WM) to explore the differences in possible target proteins and molecular pathways between CHM and WM. The application programming interface (API) was used to assess these online databases to obtain the latest biomedical information. RESULTS About 13.7% of patients were classified as CHM users among eligible DKD patients. The median follow-up duration of all patients was 2.49 years. The cumulative incidence of mortality among the CHM cohort was significantly lower than the WM cohort (28% versus 48%, P < .001). The risk of mortality was 0.41 among the CHM cohort with covariates adjustment (99% CI: 0.38-0.43, P < .001). A total of 173,525 CHM prescriptions were used to construct CMN with eleven CHM clusters. CHM covered more DKD-related proteins and pathways than WM; nevertheless, WM aimed at DKD more specifically. From the overrepresentation tests carried by the online website Reactome, the molecular pathways covered by the CHM clusters in CMN and WM seemed distinctive but complementary. The complementary effects were also found among DKD patients with concurrent WM and CHM use. The risks of mortality among CHM users under renin-angiotensin-aldosterone system (RAAS) inhibition therapy were lower than CHM nonusers among DKD patients with hypertension (adjusted HR: 0.47, 99%CI: 0.45-0.51, P < .001), chronic heart failure (adjusted HR: 0.43, 99%CI: 0.37-0.51, P < .001), and ischemic heart disease (adjusted HR: 0.46, 99%CI: 0.41-0.51, P < .001) CONCLUSIONS CHM users among DKD patients seemed to have a lower risk of mortality, which may benefit from potentially synergistic renoprotection effects. The framework of integrating real-world clinical databases and web-based biomedical databases could help explore the role of treatments for diseases.



2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Zhenzhen Lu ◽  
Yifei Zhong ◽  
Wangyi Liu ◽  
Ling Xiang ◽  
Yueyi Deng

Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes and is one of the main causes of end-stage renal disease (ESRD) in many countries. The pathological features of DKD are the hypertrophy of mesangial cells, apoptosis of podocytes, glomerular basement membrane (GBM) thickening, accumulation of extracellular matrix (ECM), glomerular sclerosis, and tubulointerstitial fibrosis. The etiology of DKD is very complicated and many factors are involved, such as genetic factors, hyperglycemia, hypertension, hyperlipidemia, abnormalities of renal hemodynamics, and metabolism of vasoactive substances. Although some achievements have been made in the exploration of the pathogenesis of DKD, the currently available clinical treatment methods are still not completely effective in preventing the progress of DKD to ESRD. CHM composed of natural products has traditionally been used for symptom relief, which may offer new insights into therapeutic development of DKD. We will summarize the progress of Chinese herbal medicine (CHM) in the treatment of DKD from two aspects. In clinical trials, the Chinese herbal formulas were efficacy and safety confirmed by the randomized controlled trials. In terms of experimental research, studies provided evidence for the efficacy of CHM from the perspectives of balancing metabolic disorders, reducing inflammatory response and oxidative stress, antifibrosis, protecting renal innate cells, and regulating microRNA and metabolism. CHM consisting of different ingredients may play a role in synergistic interactions and multiple target points in the treatment of DKD.



Author(s):  
Fatima Rodriguez ◽  
Donghyun J. Lee ◽  
Sanchit S. Gad ◽  
Matheus P. Santos ◽  
Robert J. Beetel ◽  
...  


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yuyang Wang ◽  
Hailing Zhao ◽  
Qian Wang ◽  
Xuefeng Zhou ◽  
Xiaoguang Lu ◽  
...  

Diabetic kidney disease (DKD), a leading cause of end-stage renal disease (ESRD), has become a serious public health problem worldwide and lacks effective therapies due to its complex pathogenesis. Recent studies suggested defective autophagy involved in the pathogenesis and progression of DKD. Chinese herbal medicine, as an emerging option for the treatment of DKD, could improve diabetic kidney injury by activating autophagy. In this review, we briefly summarize underlying mechanisms of autophagy dysregulation in DKD, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), and the sirtuin (Sirt) pathways, and we particularly concentrate on the current status of Chinese herbal medicine treating DKD by regulating autophagy. The advances in our understanding regarding the treatment of DKD via regulating autophagy with Chinese herbal medicine will enhance the clinical application of Chinese medicine as well as discovery of novel therapeutic agents for diabetic patients.



BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e025653 ◽  
Author(s):  
La Zhang ◽  
Lihong Yang ◽  
Johannah Shergis ◽  
Lei Zhang ◽  
Anthony Lin Zhang ◽  
...  

ObjectivesTo provide a broad evaluation of the efficacy and safety of oral Chinese herbal medicine (CHM) as an adjunctive treatment for diabetic kidney disease (DKD), including mortality, progression to end-stage kidney disease (ESKD), albuminuria, proteinuria and kidney function.DesignA systematic review and meta-analysis.MethodsRandomised controlled trials (RCTs) comparing oral CHM with placebo as an additional intervention to conventional treatments were retrieved from five English (Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Allied and Complementary Medicine Database and Cumulative Index of Nursing and Allied Health Literature) and four Chinese databases (China BioMedical Literature, China National Knowledge Infrastructure, Chonqing VIP and Wanfang) from inception to May 2018. RCTs recruiting adult DKD patients induced by primary diabetes were considered eligible, regardless of the form and ingredients of oral CHM. Mean difference (MD) or standardised mean difference (SMD) was used to analyse continuous variables and RR for dichotomous data.ResultsFrom 7255 reports retrieved, 20 eligible studies involving 2719 DKD patients were included. CHM was associated with greater reduction of albuminuria than placebo, regardless of whether renin–angiotensin system (RAS) inhibitors were concurrently administered (SMD −0.56, 95% CI [−1.04 to –0.08], I2=64%, p=0.002) or not (SMD −0.92, 95% CI [−1.35 to –0.51], I2=87%, p<0.0001). When CHM was used as an adjunct to RAS inhibitors, estimated glomerular filtration rate was higher in the CHM than placebo group (MD 6.28 mL/min; 95% CI [2.42 to 10.14], I2=0%, p=0.001). The effects of CHM on progression to ESKD and mortality were uncertain due to low event rates. The reported adverse events in CHM group included digestive disorders, elevated liver enzyme level, infection, anaemia, hypertension and subarachnoid haemorrhage, but the report rates were low and similar to control groups. The favourable results of CHM should be balanced with the limitations of the included studies such as high heterogeneity, short follow-up periods, small numbers of clinical events and older patients with less advanced disease.ConclusionsBased on moderate to low quality evidence, CHM may have beneficial effects on renal function and albuminuria beyond that afforded by conventional treatment in adults with DKD. Further well-conducted, adequately powered trials with representative DKD populations are warranted to confirm the long-term effect of CHM, particularly on clinically relevant outcomes.PROSPERO registration numberCRD42015029293.



Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1126-P
Author(s):  
HIDDO LAMBERS. HEERSPINK ◽  
PAUL PERCO ◽  
JOHANNES LEIERER ◽  
MICHAEL K. HANSEN ◽  
ANDREAS HEINZEL ◽  
...  


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 526-P
Author(s):  
MARIANA E. GUADALUPE ◽  
GRACIELA B. ALVAREZ CONDO ◽  
FANNY E. VERA LORENTI ◽  
BETTY J. PAZMIÑO GOMEZ ◽  
EDGAR I. RODAS NEIRA ◽  
...  


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  


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