HDCN Article Review/Hyperlink

Ifudu O, Feldman J, Friedman EA

The intensity of hemodialysis and the response to erythropoietin in patients with end-stage renal disease

N Engl J Med (Feb) 334:420-425 1996

Studies from as early as the 1950s have suggested that there may be a factor in the serum of uremic patients which might impair erythropoiesis. In patients who receive suboptimal hemodialysis, it is possible that such a factor could be an important cause of resistance to rHuEPO therapy. In this report, Ifudu et al sought to explore this possibility. 135 rHuEPO-treated hemodialysis patients were studied. An initial cross-sectional analysis examined the relationship between hematocrit and several measured variables. Multivariate analysis revealed a weak independent positive correlation between hematocrit and urea reduction ratio and serum albumin (regression coefficient=0.101 and 2.41 respectively, p less than 0.05 for both). In 20 patients with an initial URR less than 65%, a 6 week prospective interventional study was performed to increase dialysis intensity. Patients were switched from an Althin Medical MCA 160 dialyzer to a Fresenius Inc. F80 dialyzer., and time was increased to 4.5 hours. This resulted in an increase in URR from 60.7% to 72.0%. The mean hematocrit increased from 28.4+/-0.8% to 32.3+/-0.7%, p=0.002. There was no statistically significant change in the rHuEPO dose from baseline to study completion.

Comment: This study demonstrates an association between dialysis dose and erythropoietic response. The interventional portion of the study is provocative, despite the small number of patients studied. However, because the intervention involved a change in several dialysis parameters (KoA, biocompatibility and flux properties of the dialyzer, and dialysis time), the study is unable to determine which was the cause of the positive effect on erythropoiesis. The improved small solute clearance (as measured by the URR) may well have mediated the effect. Alternatively, the change to high-flux dialysis may have improved the clearance of a middle molecular weight toxin which could have had a detrimental effect on erythropoiesis. The increase in dialysis time was probably too small to have had an independent effect (ex: improved fluid removal with a secondary increase in hematocrit). (Steve Fishbane, M.D., Mineola, NY)