Dr. Monica Beaulieu, MD, FRCPC, MHA (biography and disclosures)
What I Did Before
Several observational studies have linked low hemoglobin with adverse outcomes in chronic kidney disease (CKD). Nephrologists often use erythropoietin stimulating agents (ESA’s) to treat the anemia of CKD. The rationale for use has been based on observational data that higher hemoglobin is associated with improved quality of life and potentially improved cardiovascular prognosis. In other words, we presumed that by increasing hemoglobin we were improving outcomes in patients with CKD, but did not have a placebo-controlled trial to guide us….until now.
What Changed My Practice
The Trial to Reduce Cardiovascular Events with Aranesp therapy (TREAT) trial was a randomized, double blinded, placebo-controlled trial that randomized patients with type 2 diabetes, chronic kidney disease and anemia to placebo or darbepoetin. Patients in the treatment arm were initiated on darbopoeitin when their Hb fell to 110g/L, with a target of 130 g/L.
There was no difference in death, nonfatal cardiovascular events, or end-stage renal disease between the groups. Patients in the darbepoetin group required fewer blood transfusions and had a very minimal benefit on quality of life (QOL) scores.
Patients in the darbepoetin group had a higher risk of stroke (fatal and nonfatal) and thromboembolic events (both venous and arterial). In addition, among patients with a history of a malignant condition at baseline, more patients in the darbepoeitin group died from cancer.
What I Do Now
This important study is concordant with other recent studies in patients with CKD not on dialysis. The bottom line is that the evidence strongly suggests that there is little to no benefit gained by raising the Hb over > 100g/L (and perhaps even lower) in diabetic patients with CKD not on dialysis. The risk of harm was also highlighted in this study with an increased risk of ischemic stroke, thromboembolism, and cancer-related death in patients with a pre-existing diagnosis of cancer.
We now initiate therapy only when the hemoglobin is <100g/L for most patients. Our therapeutic target has generally been between 110 -125 g/L, and we now aim for the lower end of the target. We predict that even the therapeutic target of 110-125 g/L may be reviewed in the near future and we do not tend to increase the dose of ESA in patients with Hb between 100-110 g/L if they are unlikely to benefit from a QOL perspective.
We are more cognizant of the risk of malignancy (also supported by other trials) and avoid ESA’s in patients with potentially curable cancers or in patients with previous history of malignancies with the potential to recur.
In addition, we proceed with a more in depth risk-benefit discussion with all patients, specifically in terms of the minimal benefit in QOL and the heightened risk of stroke.
Patients awaiting kidney transplant may be one group who may benefit from the reduced need for blood transfusions (to prevent the development of antibodies).
We encourage primary care providers and non-nephrologists caring for patients with CKD related anemia to ensure that patients are iron replete (targeting a transferrin saturation of at least 0.22) which will improve the Hb in the majority of patients with CKD related anemia. Iron therapy is under-utilized in the non-nephrologist referred CKD population. Referral to nephrology specifically for the initiation of ESA’s should only be considered in those patients with Hb <100 g/L despite adequate iron supplementation where you feel that the patient could benefit from a quality of life perspective or because of the need for fewer blood transfusions.
Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D et al. The TREAT Investigators. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease. N Engl J Med. 2009 Oct 30. Article Request Form. Note: Direct article downloads and article requests require a login ID with the BC College of Physicians website