Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

Abstract

Patients suffering from chronic renal failure have a higher burden of cardiovascular events, which increases in a dose-dependent fashion as renal function worsens. Increased cardiovascular risk in these patients is thought to be mediated by the simultaneous presence of both traditional and non-traditional cardiovascular risk factors, the latter being associated with renal impairment. Red blood cells are usually considered as carries of nutrients for tissues and respiratory gases, less so as compartments essential to vascular integrity. However, erythrocyte number, size, and integrity seem to severely affect cardiovascular morbidity and mortality as established in recent clinical studies with large patient cohorts. In particular, the role of red blood cells in chronic renal failure tends only to be considered exclusively in relation to a change in their number. However, these cells in the uremic milieu are prone to many alterations, which may adversely affect the cardiovascular system. In this review, we highlight the main qualitative erythrocyte alterations that may have a pathophysiologic role in the elevated cardiovascular risk of chronic renal failure.

Blood Cell Proteomics in Chronic Kidney Disease

“…To be noted that exposure of PS on uremic RBC membrane is expected to promote not only cell removal [59], but also procoagulant properties [60], and increased adhesion to endothelium decreasing NO release [61], an effect associated with CV mortality in ESRD. These findings may shed some light on the erythrocyte pathophysiology in ESRD, and further support the potential role of uremic RBCs per se as CV risk factor [37].…”

“…The main cause of renal anemia is a reduced erythropoietin (EPO) production, though shortened RBC lifespan, uremic toxins, and inflammation also play a role [36]. Besides a reduction in their number, erythrocytes in the uremic milieu are also prone to many structural and functional impairments, including alterations in the production of nitric oxide, reduced antioxidant activity, increased adhesion to the endothelium and pro-coagulant activity, and modification in the composition of plasma membrane, all aspects that may jeopardize their properties [37].…”

Predialysis and Dialysis Therapies Differently Affect Nitric Oxide Synthetic Pathway in Red Blood Cells from Uremic Patients: Focus on Peritoneal Dialysis

“…Indeed, we and others have shown that RBCs form NO through nitrite reduction under hypoxia conditions and synthesize NO through an active endothelial nitric oxide synthase (eNOS) during normoxia, both contributing to the circulating NO pool [ 5 , 6 , 7 , 8 ]. These findings have raised the idea that alterations in such and other RBCs functions may lead to increased cardiovascular risk as already hypothesized in diabetes mellitus, coronary artery disease (CAD), hypertension and CKD [ 8 , 9 , 10 , 11 , 12 , 13 ].…”

“…Therefore, as the uremic environment has been shown to impair several RBCs functions [ 13 ], studying the effects that the different therapies used in CKD could have on RBCs changes would add an important piece of knowledge to this intricate scenario.…”

MALDI TOF Mass Spectrometry Imaging of Blood Smear: Method Development and Evaluation

“…Different mechanical obstacles that may exist in circulation cause visible deformation of the blood cells. Even blood plasma chemistry changes, caused by some liver or kidney diseases, lead to specific RBC membrane chemical changes that manifest themselves as deformations detectable by light microscopy [ 2 ]. Unfortunately, the light microscopy of native or even stained blood smears cannot detect chemical signatures carried by blood cells which are caused by other organ pathologies.…”