In their recently published article, Sakaguchi et al.1 analyzed data from the renal registry of the Japanese Society for Dialysis Therapy (comprising 194,698 patients on hemodialysis followed for a median time of 2 years) and found increased mortality (13%) in patients treated with long-acting erythropoiesis-stimulating agents, namely darbepoetin and epoetin β pegol, when compared with epoetins (α, β, and κ) with a shorter biologic t1/2.
These authors performed a survival analysis using Cox proportional hazard models adjusted for various covariates known to influence survival in patients on dialysis.1 In addition to the factors included in their models, other confounding factors are also known to influence mortality in patients with ESKD on hemodialysis and should also be analyzed as covariates. These include the Charlson comorbidity index (validated in both patients on hemodialysis and peritoneal dialysis worldwide, and which includes items other than age, diabetes, and cardiovascular disease per se) and also the type of vascular access (native fistula versus catheter, although the percentage of dialysis catheters is known to be low in Japan).2
Most importantly, two other factors related to the dialysis technique itself should also be analyzed in Cox proportional hazard models as time-dependent covariates because they could strongly influence mortality and lead to spurious conclusions: First, the type of dialysis membrane: Abe et al.3 (who were involved in the study published in JASN) analyzed the same registry in Japan in 2017 and elegantly showed that polymethyl methacrylate and polyethersulfone dialysis membranes were associated with a lower probability of death after 2 years of follow-up in patients with ESKD treated by hemodialysis (polymethyl methacrylate, −16%; polyethersulfone, −12%). Second, more recently, Mercadal et al.4 of the French dialysis registry (Renal Epidemiology and Information Network) highlighted an increased risk of death as high as 40% in French patients with ESKD on hemodialysis that was associated with the use of citrate dialysates as compared with classic dialysates containing either acetate or hydrochloric acid, leading the French Drugs and Devices Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé) to implement a national materiovigilance survey.
Finally, in Sakaguchi et al.’s study,1 the lack of analysis of the influence (protective, neutral, or detrimental) of oral and parental (low-dose) iron therapy limits the validity of the conclusions. Thus, detailed analyses of all possible confounding factors are mandatory before considering that long-acting erythropoiesis-stimulating agents (darbepoetin and epoetin β pegol) are deleterious in patients with ESKD on hemodialysis.
Disclosures
None.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
References
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