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

Abstract

Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative therapy, CT) and dialysis (peritoneal dialysis, PD; hemodialysis, HD) therapies used during CKD progression may differently affect NO-synthetic pathway in RBCs. Our data demonstrated that compared to PD, although endothelial-NO-synthase activation was similarly increased, HD and CT were associated to cGMP RBCs accumulation, caused by reduced activity of cGMP membrane transporter (MRP4). In parallel, plasma cGMP levels were increased by both CT and HD and they significantly decreased after hemodialysis, suggesting that this might be caused by reduced cGMP renal clearance. As conceivable, compared to healthy subjects, plasma nitrite levels were significantly reduced by HD and CT but not in patients on PD. Additionally, the increased carotid intima-media thickness (IMT) values did not reach the significance exclusively in patients on PD. Therefore, our results show that PD might better preserve the synthetic NO-pathway in CKD-erythrocytes. Whether this translates into a reduced development of uremic vascular complications requires further investigation.

In Sickness and in Health: Erythrocyte Responses to Stress and Aging

“…Among these, a compensatory increase of RBC-NO synthase activation is included. In their article Palmerini et al [9] reported the impact of renal disease stage and therapeutic strategy (conservative therapy in stage 3 or 4 patients, peritoneal dialysis or hemodialysis in stage 5 patients) on the synthetic NO pathway activity in RBC from uremic patients. They found that the typical three therapeutic approaches affect at a variable way the ATPase activity of the cyclic guanosine monophosphate (cGMP, a biological effector of NO) transporter located on the RBC membrane, leading to lower efflux, and thus to higher cGMP accumulation inside RBC in conservative therapy and hemodialysis compared to the peritoneal dialysis.…”