Critiques of Clinical Guidelines in Nephrology: Anaemia

Abstract

Chronic kidney disease (CKD) is characterised by reduced erythropoietin production and anaemia. The introduction in the late 1980s of recombinant human erythropoietin transformed the quality of life and the blood transfusion requirements of patients with advanced CKD, and several erythropoietin analogues or derivatives with the collective name of erythropoiesis-stimulating agents (ESAs) are now available. However, despite the treatment of hundreds of thousands of patients with ESAs there have still been relatively few randomised controlled trials comparing outcomes at pre-specified haemoglobin (Hb) concentrations. Several unanswered questions remain regarding the optimal use of ESAs, including the ideal target Hb level for an individual and a CKD population. The conclusion from the available interventional studies is that there is no evidence for a beneficial effect of complete correction of Hb and there is weak evidence of harm with an increase in cardiovascular events and mortality. This has prompted some renal advisory bodies to modify their guidance on ESA prescribing. This critique reviews current clinical guidelines and recommendations, their scientific basis, and identifies areas of controversy including the role of newer agents, the long-term safety of ESAs, the influence of the pharmaceutical industry, and the associated healthcare costs.

2009

“…T he recombinant human erythropoietins (rHuEPOs; epoetins) and allied proteins (epoetin alfa, attempted copies and biosimilar variants of epoetin alfa, epoetin beta, epoetin delta, epoetin zeta, epoetin theta, epoetin omega, darbepoetin alfa, and methoxy-polyethylene glycol-epoetin beta) are among the most successful and earliest examples of biotechnologically manufactured products to be used in clinical medicine (1). In the past two decades, they have been used in more than 1,000,000 patients, mainly in those with chronic kidney diseases (CKDs).…”

Potency, Proliferation and Engraftment Potential of Stem Cell Therapeutics: The Relationship between Potency and Clinical Outcome for Hematopoietic Stem Cell Products

“…In a clinical setting, for example in patients suffering from anemia of chronic renal disease, administration of EPO results in a dose-dependent clinical outcome, namely the alleviation of the anemia [5,6]. In other cases, such as the anemia associated with some cancers, the administration of EPO may not have any effect and therefore a clinical outcome may not be observed [7]. In this case, potency will not correlate with clinical outcome.…”

Progress in the Detection of Erythropoietin in Blood, Urine, and Tissue

“…Until the use of erythropoiesis-stimulating agents (ESAs), blood transfusion was the main way to treat patients with renal anemia. Frequent blood transfusions have caused the spread of Hepatitis C among patients undergoing hemodialysis [25][26][27][28][29]. ESAs and Prolyl Hydroxylase Domain (PHD) inhibitors have largely changed the treatment of patients with renal anemia [15][16][17][18][19][30][31][32][33][34][35][36].…”