GFR is a Key Determinant of Red Blood Cell Survival in Anemia Associated With Progressive CKD.

INTRODUCTION: Anemia is a common and clinically significant complication observed in patients with chronic kidney disease (CKD), resulting from complex interactions between renal dysfunction, erythropoietin (EPO) deficiency, and altered iron metabolism. In murine CKD models, red blood cell (RBC) death or eryptosis, characterized by exposure of phosphatidylserine (PS) on the outer membrane of RBCs, was observed to drive anemia. However, there is limited research that has investigated this phenomenon in patients with non-dialysis-dependent CKD (NDD-CKD). METHODS: In this cross-sectional cohort study, we describe the relationship between RBC death and anemia in all stages of NDD-CKD (n = 122). Blood samples from 133 healthy blood donors were additionally analyzed as controls. RESULTS: Patients with CKD had a significantly lower hemoglobin (Hb) concentration (12.4 [interquartile range: 11.1-13.7] g/dl) when compared with the healthy group (13.8 [13.0-14.8] g/dl, P < 0.001). Hb concentrations exhibited a significant positive correlation with the estimated glomerular filtration rate (eGFR) across the entire cohort (r = 0.5, P < 0.001). RBC death rates, quantified by the binding of freshly isolated RBCs to the ligand annexin V using flow cytometry (FACS), were significantly increased by approximately 1.4-fold in patients with CKD compared with the RBC death rates in healthy blood donors. RBC death correlated with the glomerular filtration rate (GFR) stage but not with the albuminuria stage of CKD, the degree of anemia, and serum iron concentration. Using multiple linear regression, eGFR was identified as the sole independent predictor of RBC death with an inverse relationship. CONCLUSION: RBC death is stimulated in progressive NDD-CKD, possibly contributing to the development of renal anemia.