Effects of an Angiotensin II Receptor Antagonist and Angiotensin-Converting Enzyme Inhibitors on Burst Forming Units-Erythroid in Chronic Hemodialysis Patients

Abstract

Background: Angiotensin-converting enzyme (ACE) inhibitors have been reported to reduce the response to erythropoietin (EPO) administration in chronic hemodialysis patients, but the mechanism for this effect has not yet been clarified. To clarify the mechanism of ACE inhibitors- and angiotensin II type 1 (AT1) receptor antagonist-induced anemia in hemodialysis patients, we examined the effect of ACE inhibitors and AT1 receptor antagonist on burst-forming units-erythroid (BFU-E) in the peripheral blood of hemodialysis patients and healthy controls in vitro. Methods: Peripheral blood mononuclear cells (PBMNCs) were isolated by gradient centrifugation from 10 patients on regular hemodialysis and 7 healthy control volunteers. A colony assay of hematopoietic progenitors was performed using the methylcellulose culture system. PBMNCs of 1 or 2 × 10⁵ were plated in a medium containing EPO with various concentrations of ACE inhibitors or AT1 receptor antagonist and incubated for 14 days. Colonies of BFU-E were counted under an inverted microscope. Results: The PBMNCs from the chronic hemodialysis patients formed fewer BFU-Es than those from healthy volunteers. AT1 receptor antagonist in both healthy volunteers and hemodialysis patients suppressed the number of BFU-Es. The ACE inhibitors produced a smaller effect than the AT1 receptor antagonist. Conclusion: AT1 receptor blockade can directly inhibit erythropoiesis in vitro.

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

“…Repetitive BFU-E expansion and/or peripheral recruitment during decompensations may later contribute to their quantitative exhaustion in the compensated state. While ACE-inhibitors, ARBs and β 2 -adrenergic receptor blockers could also account for low BFU-E counts in our anaemic subjects [40,41], the use of these drugs did not differ between anaemic and non-anaemic patients, suggesting that other factors intrinsic to the deranged milieu of CHF were more likely responsible.…”

Advanced heart failure and nocturnal hypoxaemia due to central sleep apnoea are associated with increased serum erythropoietin

“…Angiotensin converting enzyme inhibitor therapy reduces the response to EPO among dialysis patients 24 and in vitro evidence suggests that the angiotensin II receptor blocker losartan directly suppresses erythroid blast formation. 25 It has been suggested that diuretics which act primarily on the proximal tubule may inhibit EPO production mediated via an increase of local oxygen tension. 26 However, our study did not suggest a relationship between HF medication and serum EPO concentration.…”

Anaemia correction in predialysis elderly patients: influence of the antihypertensive therapy on darbepoietin dose

“…The high prevalence of hypertension (77.5% of our These two groups of antihypertensive agents are particularly recommended in patients with chronic renal insufficiency [11][12][13][14], but the blockade of the renin-angiotensin axis that they produce can worsen anaemia. Several mechanisms have been described in the literature: prevention of the stimulatory effect of angiotensin II on the synthesis of erythropoietin; increase renal plasma flow, reducing the hypoxic stimulus for erythropoietin formation; diminished precursors of erythropoietin; direct effect on red blood stem cells [17]. These drugs are particularly indicated in CKD patients because, with one exception [10], all other studies have been shown them to delay the progression of renal disease [11,12].…”

“…However, both drugs have been shown to worsen anaemia in uraemic patients [15,16]. The pathogenesis of anaemia associated with the blockade of the renin-angiotensin axis is multifactorial [17].…”