Confounding factors of hazards of long-acting ESA

What is it about?

Recombinant erythropoietin (epoetin) in the eighties has represented for patients suffering from end-stage kidney disease ( ESKD) and their nephrologists a therapeutic revolution. Epoetins have a short biological half-life and must be administered thrice weekly at the end of the dialysis sessions. Long-acting erythropoiesis stimulating agents (ESA) (namely Darbepoetin and Epoetin beta pegol ) have been more recently engineered and are administered either once weekly ( Darbepoetin) or once monthly (Epoetin beta pegol). It was until now, widely considered that epoetins and long-acting ESAs had the same efficacy and similar side-effects. The recent analysis from the registry of the Japanese Society for Dialysis Therapy (comprising 194,968 prevalent patients on hemodialysis followed for a median time of 2 years) found an increased mortality (13%) in patients treated by long-acting ESAs (Darbepoetin and Epoetin beta pegol) as compared to epoetins (alfa, beta and kappa).

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Photo by Laura Ockel on Unsplash

Photo by Laura Ockel on Unsplash

Why is it important?

In their statistical analyses, the authors performed survival analysis using Cox proportional hazard models adjusted for various covariates known to influence survival in dialysis patients (these covariates were filled in their mega database).Unfortunately, the authors could not analyzed the influence of other confounding factors known to be of paramount importance and to certainly influence mortality in ESKD patients on hemodialysis (since they were not filled in this data base) as the Charlson comorbidity index (validated both in hemodialysis and peritoneal dialysis patients worldwide and considered as the best predictor of death in these populations) and also the type of vascular access. Finally the lack of analysis of influence of iron therapy and type of dialysis membranes like polymethylmethacrylate (PMMA) and polyethersulfone (PES) dialyzers which have been associated in Japan with lower probability of death after 2 years of follow-up (PPMA: - 16%; PES: - 12%), preclude also definitive conclusions.

Perspectives