ACE Inhibitors and anemia

ACE Inhibitors and anemia

Angiotensin converting enzyme (ACE) inhibitors have been implicated in the worsening of anemia in patients with chronic kidney disease (CKD) on dialysis and renal transplant recipients. Both ACE inhibitors and angiotensin receptor blockers (ARB) have some effect on erythropoietin synthesis and can cause suppression of erythropoiesis in those with CKD. This can sometimes be overcome by escalating the dose of exogenously administered erythropoietin. It is known that activation of renin-angiotensin system enhances the production of erythropoietin in peritubular fibroblasts of the kidney. Some studies also suggest that ACE inhibitors and ARBs suppress the effect of erythropoietin, while others do not.

Ishani A et al [1], using the Studies Of Left Ventricular Dysfunction (SOLVD) database showed that enalapril increased the odds of incident anemia at one year. Still enalapril was protective of overall mortality after adjustment for incident anemia.

ACE inhibitors have been shown to reduce hemoglobin level in those with post transplant erythrocytosis, high altitude polycythemia and in those on chronic hemodialysis. In vitro studies have suggested that angiotensin II stimulate erythroid precursors through AT1 receptors on them. ACE inhibitors can lower levels of insulin like growth factors which are also involved in erythroid stimulation. Yet another mechanism proposed is the inhibition of catabolism of N-acetyl-seryl-aspartyl-proline, an inhibitor of proliferation of red cell precursors [1].

Another study involving 96 patients with heart failure also concluded that ACE inhibitors are associated with anemia. They noted that perindopril had a higher risk than ramipril when used in heart failure patients in their study [2].

References

1. Ishani A, Weinhandl E, Zhao Z, Gilbertson DT, Collins AJ, Yusuf S, Herzog CA. Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2005 Feb 1;45(3):391-9.
2. Guirguis K. Anaemia in heart failure patients: the prevalence of haematinic deficiencies and the role of ACE inhibitors and aspirin doses as risk factors. Pharm Pract (Granada). 2019 Jan-Mar;17(1):1406.