Front Physiol. 2015 Jun 3;6:167. doi: 10.3389/fphys.2015.00167. eCollection 2015.
Erythropoietin (Epo) is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs). Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo production by REPs causes renal anemia and anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic hypoxia-responsive cells to dynamic fibrogenic cells. In chronic kidney disease, REPs are the major source of scar-forming myofibroblasts and actively produce fibrogenic molecules, including inflammatory cytokines. Notably, myofibroblast-transformed REPs (MF-REPs) recover their original physiological properties after resolution of the disease insults, suggesting that renal anemia and fibrosis could be reversible to some extent. Therefore, understanding the plasticity of REPs will lead to the development of novel targeted therapeutics for both renal fibrosis and anemia. This review summarizes the regulatory mechanisms how hypoxia-inducible Epo gene expression is attained in health and disease conditions.
OBJECTIVE: The aim was to investigate the efficacy and safety of erythropoietin (EPO) to prevent acute kidney injury (AKI) in patients with critical illness or perioperative care. METHODS: Randomized controlled trials comparing EPO with placebo for AKI prevention in adult patients with critical illness or perioperative care were searched in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, and Clinical Trials.gov until October 2014. The outcomes of interest included the incidence of AKI, dialysis requirement, mortality, and adverse event. Fixed effect model was used to calculate the pooled risk ratio (RR) and 95% confidence interval (CI) for eligible studies. RESULTS: Ten randomized controlled trials involving 2759 participants were identified and included in the analysis. Compared with placebo, EPO administration did not reduce the incidence of AKI (RR, 0.97; 95% CI, 0.79-1.19; P = 0.782), dialysis requirement (RR, 0.72; 95% CI, 0.31-1.70; P = 0.457), or mortality (RR, 0.96; 95% CI, 0.78-1.18; P = 0.705). Moreover, EPO had no effect on the risk of adverse events, but estimations of RR were difficult due to their relatively infrequent occurrence. CONCLUSIONS: This meta-analysis suggests that prophylactic administration of EPO in patients with critical illness or perioperative care does not prevent AKI, dialysis requirement, or mortality.