Erythropoiesis stimulating agents and reno-protection: a meta-analysis

Abstract

BackgroundErythropoiesis stimulating agents (ESAs) were proposed to enhance survival of renal tissues through direct effects via activation of EPO receptors on renal cells resulting in reduced cell apoptosis, or indirect effects via increased oxygen delivery due to increased numbers of Hb containing red blood cells. Thus through several mechanisms there may be benefit of ESA administration on kidney disease progression and kidney function in renal patients. However conflicting ESA reno-protection outcomes have been reported in both pre-clinical animal studies and human clinical trials. To better understand the potential beneficial effects of ESAs on renal-patients, meta-analyses of clinical trials is needed.MethodsLiterature searches and manual searches of references lists from published studies were performed. Controlled trials that included ESA treatment on renal patients with relevant renal endpoints were selected.ResultsThirty two ESA controlled trials in 3 categories of intervention were identified. These included 7 trials with patients who had a high likelihood of AKI, 7 trials with kidney transplant patients and 18 anemia correction trials with chronic kidney disease (predialysis) patients. There was a trend toward improvement in renal outcomes in the ESA treated arm of AKI and transplant trials, but none reached statistical significance. In 12 of the anemia correction trials, meta-analyses showed no difference in renal outcomes with the anemia correction but both arms received some ESA treatment making it difficult to assess effects of ESA treatment alone. However, in 6 trials the low Hb arm received no ESAs and meta-analysis also showed no difference in renal outcomes, consistent with no benefit of ESA/ Hb increase.ConclusionsMost ESA trials were small with modest event rates. While trends tended to favor the ESA treatment arm, these meta-analyses showed no reduction of incidence of AKI, no reduction in DGF or improvement in 1-year graft survival after renal transplantation and no significant delay in progression of CKD. These results do not support significant clinical reno-protection by ESAs.

Risk Factors for Recurrent Acute Kidney Injury in a Large Population-Based Cohort

“…Whether identification and treatment of potentially reversible causes of anemia or treatment of anemia can positively influence the risk for recurrent AKI without causing significant adverse effects is unknown. 29 In terms of potentially modifiable risk factors, we found that severe hypertension (ie, systolic blood pressure > 180 mm Hg) was an independent risk factor for recurrent AKI. It has been previously shown that among severely hypertensive individuals, AKI is a common complication and is associated with increased morbidity and mortality.…”

Erythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial

“…Thus, in trauma patients EPO could the expected to have some protective effects within 24‐48 hours after injury. Despite experimental and evidence, a lack in positive effects on renal function has been shown in patients undergoing kidney transplantation and in this study, in TBI patients with trauma . It needs to be noted that the renal endpoints we studied, that is, KDIGO although relevant, may be too crude to detect smaller changes in renal function.…”

“…Enrolled patients received either weekly doses of 40 000 IU of subcutaneous epoetin alfa (Eprex Janssen‐Cilag Pty Ltd, Titusville, NJ, USA) or placebo (0.9% sodium chloride). The randomization process and administration of drug has been described previously . The administration of EPO continued until patients had received a maximum of three doses, or until the patients was discharged from the ICU .…”

“…The use EPO for prevention of AKI has been studied in patients undergoing cardiac surgery and following renal transplantation, but thus far the data are conflicting . No studies have assessed the effect of EPO on kidney function in patients with trauma . Accordingly, we aimed to assess the incidence and factors increasing the likelihood as well as survival association of AKI in patients with moderate to severe TBI.…”

Advances in Understanding the Effects of Erythropoietin on Renal Fibrosis

“…Elliott et al found that EPO-R protein was below the detection limit in tissues and renal cells and no evidence of EPO-R expression and function in the kidneys (33). A subsequent meta-analysis of clinical trials by Elliott et al showed that ESAs had no clear renoprotective effect, at least in the included subjects (34). Thus, it is currently controversial whether functional EPO-R occurs on the plasma membranes of renal cells.…”