scholarly journals The Dilemma of Dual Renin-Angiotensin System Blockade in Chronic Kidney Disease: Why Beneficial in Animal Experiments But Not in the Clinic?

2017 ◽  
pp. 181-192 ◽  
Author(s):  
V. ČERTÍKOVÁ CHÁBOVÁ ◽  
L. ČERVENKA
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Studies ◽  
Enzyme Inhibitors ◽  
Animal Experiments ◽  
Renin Angiotensin System ◽  
Dual Therapy ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin

Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients.

Intraoperative Hyperkalemia

2018 ◽  
pp. 269-274
Author(s):  
M. Angele Theard ◽  
Alexandra Bastien
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Close Monitoring ◽  
Converting Enzyme Inhibitors ◽  
Renin Inhibitors ◽  
Increased Risk ◽  
Receptor Blockers

Patients with hypertension, diabetes, and heart disease are at risk for chronic kidney disease and therefore require close monitoring of potassium (K+) levels in order to avoid some of the more concerning consequences of hyperkalemia. Medical therapy in these patients, which often includes angiotensin converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and mineralocorticoid receptor antagonists, while helpful in managing some of the aforementioned comorbidities and ameliorating chronic kidney disease in these patients, places them at increased risk for unwanted K+ elevations. Symptoms of hyperkalemia maybe nonspecific (fatigue, weakness, and gastrointestinal upset), requiring attention therefore to preoperative laboratory analysis to avert the potentially lethal intraoperative consequences of hyperkalemia like asystole and ventricular fibrillation. Emergency surgery in these patients after trauma complicated by crush injury is particularly challenging requiring that the anesthesiologist be well-versed in recognizing the signs of and managing intraoperative hyperkalemia.

scholarly journals Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study

2019 ◽  
Vol 12 (5) ◽  
pp. 663-672 ◽  
Author(s):  
Insa M Schmidt ◽  
Silvia Hübner ◽  
Jennifer Nadal ◽  
Stephanie Titze ◽  
Matthias Schmid ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Enzyme Inhibitors ◽  
Medication Use ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Median Number ◽  
Converting Enzyme Inhibitors ◽  
Ckd Stage ◽  
Multiple Drugs

Abstract Background Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce. Methods A total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR ≥60 mL/min/1.73m2 and overt proteinuria (>500 mg/day) were studied. Self-reported data on current medication use were assessed at baseline (2010–12) and after 4 years of follow-up (FU). Prevalence and risk factors associated with polypharmacy (defined as the regular use of five or more drugs per day) as well as initiation or termination of polypharmacy were evaluated using multivariable logistic regression. Results The prevalence of polypharmacy at baseline and FU was almost 80%, ranging from 62% in patients with CKD Stage G1 to 86% in those with CKD Stage G3b. The median number of different medications taken per day was eight (range 0–27). β-blockers, angiotensin-converting enzyme inhibitors and statins were most frequently used. Increasing CKD G stage, age and body mass index, diabetes mellitus, cardiovascular disease and a history of smoking were significantly associated with both the prevalence of polypharmacy and its maintenance during FU. Diabetes mellitus was also significantly associated with the initiation of polypharmacy [odds ratio (OR) 2.46, (95% confidence interval 1.36–4.45); P = 0.003]. Conclusion Medication burden in CKD patients is high. Further research appears warranted to address the implications of polypharmacy, risks of drug interactions and strategies for risk reduction in this vulnerable patient population.

scholarly journals Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Keiichi Ikeda ◽  
Tsuyoshi Isaka ◽  
Kouki Fujioka ◽  
Yoshinobu Manome ◽  
Katsuyoshi Tojo
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Channel Blockers ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin ◽  
Aldosterone Production ◽  
Ras Inhibitors

Aldosterone, a specific mineralocorticoid receptor (MR) agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin II type 1 receptor antagonists (ARBs). However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS) inhibitors) gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+channel blockers (CCBs) have inhibitory actions on aldosterone production inin vitroand in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

scholarly journals The impact of ramipril on kidney function parameters in the chronic kidney disease patient with hypertension

2020 ◽  
Vol 11 (4) ◽  
pp. 6932-6937
Author(s):  
Mohammed Salim KT ◽  
Saravanakumar RT ◽  
Dilip C ◽  
Amrutha KP
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Enzyme Inhibitors ◽  
Disease Patient ◽  
Cost Effective ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Cost Effective Technique ◽  
The Impact

The administration of angiotensin converting enzyme inhibitors had gain popularity owing to their efficacy and safety in chronic kidney disease (CKD) patients. However, it is certainly necessary to look into the impact of the ramipril in kidney impaired individuals. We had enrolled 190 CKD with hypertensive patients based on the exclusion and inclusion criteria. The elder patients constituted to have a major share in the CKD population on ramipril therapy. From the study, it was found that the high costly brand was chosen the most and least cost was preferred only for 2 patients. The glomerular filtration rate (GFR) and serum creatinine, the major determinants of kidney function, had a small relationship with the dose of ramipril. However, the antihypertensive drug showed to have a favorable impact on patients overall treatment outcome. It is vital to evaluate the amount of protein in urine in case of a CKD patient. The easiest and cost effective technique, the dipstick urine protein test was done. The test value was found to be 1+ (30mg/dl) for majority of the patients and only 2 patients were observed with more than 1000 mg/dl. The ability of ramipril to reduce the progression of CKD can be attributed to the pooling of the data in +1 (30mg/dl) range.

scholarly journals Antisense Oligonucleotide: A Potential Therapeutic Intervention for Chronic Kidney Disease

2022 ◽  
Vol 2 (1) ◽  
pp. 16-37
Author(s):  
Yalin Li ◽  
Yuqin Tan ◽  
Rui Zhang ◽  
Tao Wang ◽  
Ning Na ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Antisense Oligonucleotide ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Public Health Issue ◽  
Global Public Health ◽  
Converting Enzyme Inhibitors ◽  
Development Platform

Chronic kidney disease (CKD) is a global public health issue that places an increasing burden on the healthcare systems of both the developed and developing countries. CKD is a progressive and irreversible condition, affecting approximately 10% of the population worldwide. Patients that have progressed to end-stage renal disease (ESRD) require expensive renal replacement therapy, i.e., dialysis or kidney transplantation. Current CKD therapy largely relies on the use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). However, these treatments by no means halt the progression of CKD to ESRD. Therefore, the development of new therapies is urgently needed. Antisense oligonucleotide (ASO) has recently attracted considerable interest as a drug development platform. Thus far, eight ASO-based drugs have been granted approval by the US Food and Drug Administration for the treatment of various diseases. Herein, we review the ASOs developed for the identification of CKD-relevant genes and/or the simultaneous development of the ASOs as potential therapeutics towards treating CKD.

Renin-Angiotensin-Aldosterone System and Migraine: A Systematic Review of Human Studies

2020 ◽  
Vol 27 (6) ◽  
pp. 512-519 ◽  
Author(s):  
Karina Lúcia Moreira Sassi ◽  
Laís Bhering Martins ◽  
Aline Silva de Miranda ◽  
Antonio Lucio Teixeira
Keyword(s):  
Systematic Review ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Migraine Treatment ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
At1 Receptor Antagonists

Migraine is a common neurologic condition marked by recurrent episodes of headache. Its pathophysiology is highly complex involving neuronal, inflammatory and vascular mechanisms. The Renin-Angiotensin System (RAS) can modulate all these mechanism, being a potential pharmacological target for migraine treatment. We carried out a systematic review of the studies evaluating the involvement of RAS in patients with migraine. There is evidence from genetic studies exploring the relation between migraine and RAS-related genes and from clinical trials evaluating the efficacy of Angiotensin II Type 1 (AT1) receptor antagonists and angiotensin converting enzyme inhibitors in migraine prophylaxis. RAS seems to play a role in the pathophysiology of migraine, but more direct evidence is still missing.

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