cardiovascular-agents and Proteinuria

There is increasing evidence that endothelin receptor blockade and, in particular, ET(A) receptor blockade not only confers protection against proteinuric renal disease in diabetes but also confers vasculoprotection.. Recent clinical trials using ET(A) receptor blockade in treating proteinuria and chronic kidney disease as well as atherosclerosis show great promise; however, adverse effects are still problematic.. Endothelin receptor blockade is associated with a significant attenuation of proteinuria and these effects are mediated in part via inhibition of inflammatory and oxidative stress related pathways as well profibrotic pathways. The addition of ET(A) receptor blockade to currently established therapies such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may result in additional or synergistic renoprotection and vasculoprotection in hypertension and, in particular, in the context of diabetes.

Topics: Animals; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Diabetic Nephropathies; Endothelin Receptor Antagonists; Endothelins; Humans; Hypertension; Kidney; Kidney Diseases; Proteinuria; Receptors, Endothelin; Signal Transduction

Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI significantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Complications; Drug Administration Schedule; Heart Failure; Humans; Hypertension; Indoles; Myocardial Infarction; Proteinuria; Treatment Outcome; Ventricular Dysfunction, Left

Management of hypertension is the mainstay of prevention and treatment of diabetic renal disease; evidence suggests that tight blood pressure control slows renal disease progression in established diabetic nephropathy. Inhibition of the renin-angiotensin-aldosterone system (RAAS) has renoprotective effects over and above those achieved by lowering systemic blood pressure. To date, however, no long-term study using hard end points has directly compared current mechanisms for RAAS inhibition, angiotensin II receptor blockade (ARB) and angiotensin-converting enzyme (ACE) inhibition. This issue was addressed in the recently published Diabetics Exposed to Telmisartan and Enalapril (DETAIL) study, a head-to-head comparison of telmisartan and enalapril in 250 patients with hypertension and type 2 diabetes mellitus and early-stage nephropathy. After 5 years' treatment, change in glomerular filtration rate (GFR), the primary efficacy end point, was equivalent in the 2 treatment groups, as were all secondary end points. The expected steep decline in GFR in the first year was followed by a lesser decrease in the second year and then almost complete stabilization of renal function at > or =3 years. Over 5 years, no patient went into end-stage renal disease or required dialysis. There were also no increases in albumin excretion rate, nor was there an increase in creatinine beyond 200 mumol/L. Incidence of cardiovascular morbidity and mortality was extremely low in both treatment groups, a remarkable outcome given that almost 50% of patients had evidence of cardiovascular disease at randomization. Inhibition of the RAAS should play a major part in management of patients with type 2 diabetes with nephropathy, for which both telmisartan and enalapril provide long-term renoprotection.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Benzoates; Cardiovascular Agents; Diabetic Nephropathies; Enalapril; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Proteinuria; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Telmisartan; Time Factors; Treatment Outcome

Optimal care of lupus nephritis patients should include the treatment of proteinuria and hypertension, other measures to delay the progression of chronic kidney disease, the vigorous management of cardiovascular risk factors and finally, the treatment of advanced chronic kidney disease and its consequences. These topics are briefly reviewed in the present paper, with particular emphasis on the recent progresses in antiproteinuric treatment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Disease Progression; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Lupus Nephritis; Patient Care; Proteinuria; Risk Factors

Topics: Aged; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Diabetic Nephropathies; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Proteinuria; Rats; Renin-Angiotensin System; Ventricular Dysfunction, Left

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Interactions; Enalapril; Female; Humans; Male; Middle Aged; Proteinuria