Review: The pharmacokinetics and pharmacodynamics of angiotensin-receptor blockers in end-stage renal disease

Abstract

Angiotensin-converting enzyme (ACE) inhibitors and more recently angiotensin-receptor blockers (ARBs) have become popular therapies in the end-stage renal disease (ESRD) patient. The ability of either of these drug classes to reduce blood pressure in the ESRD patient is well accepted; however, there is considerably less information available to guide the clinician in the safe and effective use of these drugs in the ESRD patient with congestive heart failure and/or coronary artery disease. Head-to-head studies in the ESRD patient are lacking for both drug classes. Several pharmacokinetic factors can influence the selection of these drugs, including dialysability and the propensity for systemic accumulation. ACE inhibitors (ACE-Is) and ARBs are recognised as having a range of nonpressor effects that are pertinent to patients with ESRD. Such effects include their ability to decrease both thirst drive and erythropoiesis. These drug classes, though, are distinguishable by the unique adverse effect profile for ACE-Is. As is the case in patients without renal failure, ESRD patients can experience cough and, less frequently, angioneurotic oedema with ACE-Is. In the ESRD population, so-called anaphylactoid dialyser reactions can occur in conjunction with ACE-I use. The use of a drug from within the ARB class carries both less risk and permits a compound with a preferred pharmacokinetic profile -limited dialysability and minimal systemic accumulation -to be administered. These attributes would favour the increased use of ARBs in this population.

Activation of the ACE2/Ang-(1–7)/Mas pathway reduces oxygen–glucose deprivation-induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction

“…They may lower the risk for myocardial infarction 7 , improve the treatment of patients in end stage renal disease 75 , decrease the incidence of stroke 38, 61 , and improve stroke outcome 2 . Because of the antagonist relations between the ACE2/Ang-(1-7)/Mas axis and the Ang-II/AT1 pathway, others have suggested that augmentation of Mas signaling by pharmacological or genetic methods also may be a means of improving outcomes in these pathological situations 17, 52 .…”

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…Similarly, renal impairment differentially affects ARB pharmacokinetics, with irbesartan and telmisartan not being affected even by severe renal impairment. As ARBs pharmacodynamically have beneficial effects in patients with impaired renal function and are generally classified as renoprotective, their use in such patients is generally recommended (Sica and Gehr, 2002).…”

Association of Angiotensin-Converting Enzyme Inhibitor Therapy Initiation With a Reduction in Hemoglobin Levels in Patients Without Renal Failure

“…To our knowledge, the impact of ACE-I and ARB use on inhibition of the positive hematologic effects of renin-angiotensin system activation has been studied thoroughly only in patient populations at risk for secondary erythrocytosis [5][6][7][8][9][10][11] but not in most patients taking these pharmaceuticals for indications such as diabetes, hypertension, IHD, and left ventricular dysfunction.…”