Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease

Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients. Inhibition of endothelin (ET) system in combination with established RAASis may represent such an approach. There are complex interactions between both systems and similarities in their renal physiological and pathophysiological actions that provide theoretical rationale for combined inhibition. This view is supported by some experimental studies in models of both diabetic and nondiabetic CKD showing that a combination of RAASis with ET receptor antagonists (ERAs) ameliorate proteinuria, renal structural changes, and molecular markers of glomerulosclerosis, renal fibrosis, or inflammation more effectively than RAASis or ERAs alone. Practically all clinical studies exploring the effects of RAASis and ERAs combination in nephroprotection have thus far applied add-on designs, in which an ERA is added to baseline treatment with ACEIs or ARBs. These studies, conducted mostly in patients with diabetic nephropathy, have shown that ERAs effectively reduce residual proteinuria in patients with baseline RAASis treatment. Long-term studies are currently being conducted to determine whether promising antiproteinuric effects of the dual blockade will be translated in long-term nephroprotection with acceptable safety profile.

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Diabetic nephropathy: what should cardiologist remember

Consilium Medicum ◽

10.26442/20751753.2021.1.200712 ◽

2021 ◽

Vol 23 (1) ◽

pp. 20-24

Author(s):

Natalia P. Trubitsyna ◽

◽

Natalia V. Zaitseva ◽

Anastasia S. Severinа ◽

◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Renal Replacement Therapy ◽

Renal Disease ◽

Replacement Therapy ◽

End Stage Renal Disease ◽

Kidney Diseases ◽

Renin Angiotensin Aldosterone System ◽

Stage Renal Disease ◽

End Stage

Prevalence of diabetes mellitus (DM) progressively increases around the world. Diabetic nephropathy (DN) is significant reason of end-stage renal disease and it is associated with high risk of cardiovascular disease and mortality. Necessity of expensive renal replacement therapy for patients with prominent vascular diabetic complications and end-stage renal disease has significant socio-economic impact. DM, as a one of leading causes of kidney diseases, competes for stricted resources of public health. Renal replacement therapy in patients with DM does not solve the whole problem, because survival of such patients is low, comparing with another kidney diseases, first of all because of cardiovascular diseases. Good control of glycaemia, blood pressure and cholesterol level and prescription of renin-angiotensin-aldosterone system inhibitors and statins decrease cardiovascular risk and slow down DN progression, as it was shown in many clinical trials. So patients with DM and DN should receive complex therapy for risk reduction of kidney disease and cardiovascular disorders progression. Keywords: diabetes mellitus type 2, diabetic nephropathy, nephroprotection, cardioprotection, SGLT-2 inhibitors, GLP-1 agonists, renin-angiotensin-aldosterone system For citation: Trubitsyna NP, Zaitseva NV, Severinа AS. Diabetic nephropathy: what should cardiologist remember. Consilium Medicum. 2021; 23 (1): 20–24. DOI: 10.26442/20751753.2021.1.200712

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Renin inhibition in the treatment of diabetic kidney disease

Clinical Science ◽

10.1042/cs20120468 ◽

2013 ◽

Vol 124 (9) ◽

pp. 553-566 ◽

Cited By ~ 10

Author(s):

Radko Komers

Keyword(s):

Kidney Diseases ◽

Diabetic Patients ◽

Beneficial Effects ◽

Rate Limiting Step ◽

Renin Inhibition ◽

Raas Inhibitors ◽

Stage Renal Disease ◽

End Stage ◽

Activation Cascade

Inhibition of the RAAS (renin–angiotensin–aldosterone system) plays a pivotal role in the prevention and treatment of diabetic nephropathy and a spectrum of other proteinuric kidney diseases. Despite documented beneficial effects of RAAS inhibitors in diabetic patients with nephropathy, reversal of the progressive course of this disorder or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. Incomplete inhibition of the RAAS has been postulated as one of reasons for unsatisfactory therapeutic responses to RAAS inhibition in some patients. Inhibition of renin, a rate-limiting step in the RAAS activation cascade, could overcome at least some of the abovementioned problems associated with the treatment with traditional RAAS inhibitors. The present review focuses on experimental and clinical studies evaluating the two principal approaches to renin inhibition, namely direct renin inhibition with aliskiren and inhibition of the (pro)renin receptor. Moreover, the possibilities of renin inhibition and nephroprotection by interventions primarily aiming at non-RAAS targets, such as vitamin D, urocortins or inhibition of the succinate receptor GPR91 and cyclo-oxygenase-2, are also discussed.

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Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End-Stage Renal Disease

The American Journal of the Medical Sciences ◽

10.1016/j.amjms.2015.12.021 ◽

2016 ◽

Vol 351 (3) ◽

pp. 309-316 ◽

Cited By ~ 7

Author(s):

Teresa Slomka ◽

Emily S. Lennon ◽

Hina Akbar ◽

Elvira O. Gosmanova ◽

Syamal K. Bhattacharya ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Stage Renal Disease ◽

End Stage

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A Review of the Potential Benefits of Pentoxifylline in Diabetic and Non-Diabetic Proteinuria

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3bp4g ◽

2011 ◽

Vol 14 (1) ◽

pp. 128 ◽

Cited By ~ 22

Author(s):

Shirinsadat Badri ◽

Simin Dashti-Khavidaki ◽

Mahboob Lessan-Pezeshki ◽

Mohammad Abdollahi

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Large Scale ◽

Kidney Diseases ◽

Scientific Basis ◽

Sustained Reduction ◽

Number Of Patients ◽

Stage Renal Disease ◽

End Stage

Chronic kidney disease (CKD) as a considerable health problem may have proteinuria as the main complication and strong risk factor to reach end-stage renal disease (ESRD). Decreasing proteinuria is the mainstay of therapy in order to delay the progression of CKD. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to ESRD. Pentoxifylline (PTF) is known for its potent inhibitory effects against cell proliferation and inflammation which play important roles in CKD progression. Data derived from both human studies and animal models demonstrated that PTF has broad-spectrum renoprotective effects and therefore, provide a scientific basis for the use of PTF as an anti-proteinuric agent. Conclusion of this review is that short-term use of PTF may produce a significant reduction of proteinuria in subjects with diabetic and also non-diabetic kidney diseases but the reports of long-term use of PTF also show that urinary protein excretion exhibits a progressive and sustained reduction in patients treated with PTF. Whether the long-term use of PTF could be a pharmacological alternative for delaying or preventing the development of end stage renal disease, is among the questions that remained to be appropriately answered in large-scale clinical trials.

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Diabetes and Renin-Angiotensin-Aldosterone System: Pathophysiology and Genetics

10.5772/intechopen.97518 ◽

2021 ◽

Author(s):

A.H.M. Nurun Nabi ◽

Akio Ebihara

Keyword(s):

Diabetes Mellitus ◽

Cardiovascular Diseases ◽

Kidney Diseases ◽

Association Studies ◽

Plasma Renin ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Genome Wide ◽

Renal Vascular

Diabetes mellitus (DM) is a metabolic disorder and characterized by hyperglycemia. Being a concern of both the developed and developing world, diabetes is a global health burden and is a major cause of mortality world-wide. The most common is the type 2 diabetes mellitus (T2DM), which is mainly caused by resistance to insulin. Long-term complications of diabetes cause microvascular related problems (eg. nephropathy, neuropathy and retinopathy) along with macrovascular complications (eg. cardiovascular diseases, ischemic heart disease, peripheral vascular disease). Renin-angiotensin-aldosterone system (RAAS) regulates homeostasis of body fluid that in turn, maintains blood pressure. Thus, RAAS plays pivotal role in the pathogenesis of long-term DM complications like cardiovascular diseases and chronic kidney diseases. T2DM is a polygenic disease, and the roles of RAAS components in insulin signaling pathway and insulin resistance have been well documented. Hyperglycemia has been found to be associated with the increased plasma renin activity, arterial pressure and renal vascular resistance. Several studies have reported involvement of single variants within particular genes in initiation and development of T2D using different approaches. This chapter aims to investigate and discuss potential genetic polymorphisms underlying T2D identified through candidate gene studies, genetic linkage studies, genome wide association studies.

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Renin-Angiotensin-Aldosterone System Blockade Strategies and the Risk of Acute Kidney Injury in Septic and Critically Ill Patients

10.21203/rs.2.22152/v1 ◽

2020 ◽

Author(s):

Ruey-Hsing Chou ◽

Shang-Feng Yang ◽

Cheng-Hsueh Wu ◽

Yi-Lin Tsai ◽

Ya-Wen Lu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Angiotensin Receptor Blockers ◽

Kidney Injury ◽

Secondary Outcome ◽

Converting Enzyme Inhibitors ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Raas Blockade ◽

Icu Admission

Abstract Background: Renin-angiotensin-aldosterone system (RAAS) blockers are widely used for the treatment of hypertension and heart failure, but the usage of angiotensin- converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) demands caution due to a potential risk of causing acute kidney injury (AKI). Whether long-term RAAS blockade increases AKI risk and should be withdrawn during critical illness remains inconclusive. This study aimed to investigate the associations between RAAS blockade strategies and AKI incidence in patients admitted to intensive care units (ICUs). Methods: Twenty-four hundred dialysis-free patients admitted to ICUs during December 2015–July 2017 were enrolled. Patients with pre-ICU AKI (n=568) were excluded when examining in-ICU AKI events. Patients using ACEi or ARB for more than 1 month before hospitalization were defined as long-term ACEi/ARB users. ACEi/ARB users were further grouped by ACEi/ARB continuation/withdrawal at ICU admission. Daily urine output and serum creatinine were measured in ICU. The primary outcome was occurrence of AKI within 48 hours after ICU admission, and the secondary outcome was all-cause mortality within 1 year. Results: Totally 1181 (49.2%) AKI cases and 895 (37.3%) deaths within 1 year occurred. ACEis/ARBs were continued for 122 patients and withdrawn for 239 patients. ACEi/ARB users were older and had lower initial estimated glomerular filtration rates (eGFRs). Compared with non-use, long-term ACEi/ARB use [odds ratio (OR) 1.03, 95% confidence interval (CI) 0.85–1.26, p=0.741] and continued ICU use (OR 1.14, 95% CI 0.78–1.68, p=0.491) were not associated with increased AKI risk. ACEi/ARB use was associated with less 1-year mortality. However, compared with withdrawal, continued ACEi/ARB use in ICUs was associated with higher AKI incidence among patients with sepsis (OR 2.89, 95% CI 1.35–6.20, p=0.006). Conclusions: Long-term RAAS blockade was not associated with a higher AKI or mortality incidence during acute illness. Continued ACEi/ARB use in ICUs may increase AKI risk in septic patients. Long-term and continued ACEi/ARB use are recommended, with cautious evaluation at ICU admission.

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Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease

Kidney International ◽

10.1046/j.1523-1755.2001.00769.x ◽

2001 ◽

Vol 60 (1) ◽

pp. 46-54 ◽

Cited By ~ 80

Author(s):

Emanuela Lovati ◽

Alain Richard ◽

Brigitte M. Frey ◽

Felix J. Frey ◽

Paolo Ferrari

Keyword(s):

Renal Disease ◽

Genetic Polymorphisms ◽

End Stage Renal Disease ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Stage Renal Disease ◽

End Stage

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Depression among Chronic Kidney Diseases Patients Receiving Hemodialysis

Journal of Karnali Academy of Health Sciences ◽

10.3126/jkahs.v3i2.31326 ◽

2020 ◽

Vol 3 (2) ◽

pp. 73-79

Author(s):

Shanti Khadka ◽

Rita Adhikari ◽

Tarun Paudel

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Diseases ◽

Cross Sectional ◽

Prevalence Of Depression ◽

Depression Level ◽

Western Regional ◽

Stage Renal Disease ◽

End Stage

Background: Chronic Kidney Disease (CKD) is a progressive irreversible loss of renal function over a period of months or years. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintains life. Hemodialysis is used for patients who require short term dialysis (days to weeks) and for patients with advanced CKD and End Stage renal Disease (ESRD) who require long term or permanent renal replacement therapy. Hemodialysis significantly and adversely affects the lives of patients, both physically and psychologically. Depression is the most common psychological condition among patients with ESRD. Depression in dialysis patients not only effect mortality, but increased rate of hospitalizations and dialysis withdrawal is also very common. Methods: A descriptive cross sectional research design was carried out to identify the depression level of chronic kidney disease patients receiving Hemodialysis in Western Regional Hospital, Pokhara using Beck Depression Inventory among forty six patients. Results: The study findings revealed that majority of the patients (84.8%) has various degree of depression i.e. mild (21.7%), moderate (30.8%) and severe (32.6%). Only fifteen percent of patient has no depression. There was no statistical association between the level of depression and socio-demographic variables. It can be concluded that the prevalence of depression is high among patients receiving Hemodialysis. Conclusion: The prevalence of depression is high among patients receiving Hemodialysis. It is effective to provide mental health services to the CKD patients receiving Hemodialysis which help them better psychologically adaptation to their disease and improve their quality of life.

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