The Relationship between an Oxidative Stress Biomarker and Plasma Haemoglobin in Patients with Chronic Kidney Disease

Abstract

Introduction Evidence suggests that decreased haemoglobin plasma concentration may be a predictor of adverse cardiovascular events in patients with chronic kidney disease (CKD). We hypothesized that in CKD patients, oxidative stress could influence the development of cardiovascular damage via a relationship with haemoglobin levels. Methods We assayed plasma levels of the biomarker of oxidative stress 8-ISO-prostaglandin F2α (8-ISO-PGF2α) and of haemoglobin in 193 stage 2-5 CKD patients, investigating their relationship. Eighty healthy subjects and 80 patients with primary hypertension having normal renal function were enrolled as controls. Results The CKD group was divided according to 8-ISO-PGF2α quartiles, and decreasing levels of both haemoglobin and estimated glomerular filtration rate (eGFR) along with increasing quartiles were observed. In the 193 CKD patients, the linear analysis of correlation showed inverse correlations of 8-ISO-PGF2α with both haemoglobin and eGFR (r = −0.47; r = −0.81; p < 0.00001, respectively). In the control groups, no correlation between haemoglobin and 8-ISO-PGF2α was found. The multiple regression analysis carried out in CKD patients, by a model with 8-ISO-PGF2α as the dependent variable, and including haemoglobin and all confounding factors, confirmed the inverse relationship between haemoglobin and 8-ISO-PGF2α (β = −0.50; p < 0.00001). In this model, only when eGFR was added did the relationship between haemoglobin and 8-ISO-PGF2α lose statistical significance. In this final multivariate model, 8-ISO-PGF2α correlated independently with eGFR (β = −0.82; p < 0.0001). Conclusions In CKD, haemoglobin plasma level is inversely related to oxidative stress, depending on GFR. It remains to be elucidated whether or not the biochemistry of nitric oxide and haemoglobin interaction has a role in causing this relationship.