Role of renin–angiotensin–aldosterone system inhibitors in heart failure and chronic kidney disease

Singhania, Namrata; Bansal, Saurabh; Mohandas, Shreya; Nimmatoori, Divya P; Ejaz, A. Ahsan; Singhania, Girish

doi:10.7573/dic.2020-7-3

Cited by 10 publications

(9 citation statements)

References 59 publications

(41 reference statements)

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“…They are proven to reduce mortality rates and prevent cardiovascular morbidity. In addition, they can slow the degeneration of kidney function in patients with hyperalbuminuria and pre-ESRD [72][73][74]. Some studies have declared that simultaneous use of more than one drug is a good strategy for treating DKD patients because of different mechanisms [75][76][77].…”

Section: Principal Findingsmentioning

confidence: 99%

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study

Wu¹,

Chen²,

Yang³

et al. 2021

JMIR Med Inform

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Background Diabetic kidney disease (DKD) is one of the most crucial causes of chronic kidney disease (CKD). However, the efficacy and biomedical mechanisms of Chinese herbal medicine (CHM) for DKD in clinical settings remain unclear. Objective This study aimed to analyze the outcomes of DKD patients with CHM-only management and the possible molecular pathways of CHM by integrating web-based biomedical databases and real-world clinical data. 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 for all CHM prescriptions. Further, web-based biomedical databases, including STITCH, STRING, BindingDB, TCMSP, TCM@Taiwan, and DisGeNET, were integrated with the CMN and commonly used Western medicine (WM) to explore the differences in possible target proteins and molecular pathways between CHM and WM. An application programming interface was used to assess these online databases to obtain the latest biomedical information. Results About 13.7% (20,947/131,410) 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 mortality rate in the CHM cohort was significantly lower than that in the WM cohort (28% vs 48%, P<.001). The risk of mortality was 0.41 in the CHM cohort with covariate adjustment (99% CI 0.38-0.43; P<.001). A total of 173,525 CHM prescriptions were used to construct the CMN with 11 CHM clusters. CHM covered more DKD-related proteins and pathways than WM; nevertheless, WM aimed at managing DKD more specifically. From the overrepresentation tests carried out by the online website Reactome, the molecular pathways covered by the CHM clusters in the CMN and WM seemed distinctive but complementary. Complementary effects were also found among DKD patients with concurrent WM and CHM use. The risk of mortality for CHM users under renin-angiotensin-aldosterone system (RAAS) inhibition therapy was lower than that for CHM nonusers among DKD patients with hypertension (adjusted hazard ratio [aHR] 0.47, 99% CI 0.45-0.51; P<.001), chronic heart failure (aHR 0.43, 99% CI 0.37-0.51; P<.001), and ischemic heart disease (aHR 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 in exploring the roles of treatments for diseases.

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Section: Principal Findingsmentioning

confidence: 99%

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study

Wu¹,

Chen²,

Yang³

et al. 2021

JMIR Med Inform

View full text Add to dashboard Cite

show abstract

Section: Principal Findingsmentioning

confidence: 99%

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study (Preprint)

Wu¹,

Chen²,

Yang³

et al. 2021

Preprint

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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.

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“…Primary dysfunction of one organ often leads to secondary dysfunction in another organ, resulting in a vicious cycle and eventually leading to cardiorenal syndrome [ 4 ]. Excessive activation of the renin-angiotensin-aldosterone system (RAAS) plays a key role in this process [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the RAAS plays a significant role in maintaining homeostasis of cardiovascular function and the balance of electrolytes and bodily fluids and regulating blood pressure, renal blood flow, and urine production [ 9 , 11 , 19 , 25 , 26 ].…”

Section: Brief Introduction Of the Raasmentioning

confidence: 99%

Role and Mechanism of the Renin-Angiotensin-Aldosterone System in the Onset and Development of Cardiorenal Syndrome

Gao

Liang

et al. 2022

J Renin Angiotensin Aldosterone Syst

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Cardiorenal syndrome (CRS), a clinical syndrome involving multiple pathological mechanisms, exhibits high morbidity and mortality. According to the primary activity of the disease, CRS can be divided into cardiorenal syndrome (type I and type II), renal heart syndrome (type III and type IV), and secondary heart and kidney disease (type V). The renin-angiotensin-aldosterone system (RAAS) is an important humoral regulatory system of the body that exists widely in various tissues and organs. As a compensatory mechanism, the RAAS is typically activated to participate in the regulation of target organ function. RAAS activation plays a key role in the pathogenesis of CRS. The RAAS induces the onset and development of CRS by mediating oxidative stress, uremic toxin overload, and asymmetric dimethylarginine production. Research on the mechanism of RAAS-induced CRS can provide multiple intervention methods that are of great significance for reducing end-stage organ damage and further improving the quality of life of patients with CRS.

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Role of renin–angiotensin–aldosterone system inhibitors in heart failure and chronic kidney disease

Cited by 10 publications

References 59 publications

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study (Preprint)

Role and Mechanism of the Renin-Angiotensin-Aldosterone System in the Onset and Development of Cardiorenal Syndrome

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