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Burst‐promoting activity in the serum of patients with chronic renal failure undergoing long‐term hemodialysis

Anemia in patients with chronic renal failure (CRF) is multifactorial, and while the majority will respond to the paternal administration of recombinant human erythropoietin (r‐HuEPO), a role for coexistent plasma inhibitors and stimulators, such as burst‐promoting activity (BPA), remains controversial. To evaluate the latter possibility, eight individuals with CRF on long‐term hemodialysis, were studied before (mean hemoglobin 58.4 ± 8.0 g/1 and after 12 weeks of r‐HuEPO therapy (mean hemoglobin 100.4 ± 18.3 g/1). In vitro erythroid cultures using erythroid burst forming unit (BFU‐E) and erythroid colony forming unit (CFU‐E) assays were performed, plating 5 × 104 bone marrow mononuclear cells and comparing growth in heat‐inactivated autologous serum with AB serum. Using Step III sheep erythropoietin (Connaught Laboratories, Willowdale, Ontario, Canada) (n = 4), mean BFU‐E pre‐therapy were 89.7 ± 75.1, CFU‐E were 418.5 ± 150.6, whereas the corresponding figures in AB serum were 2.5 ± 2.9 and 197 ± 94.19, p = 0.1, p — 0.01, respectively. Similarly, with r‐HuEPO (EPOCONN; Connaught Laboratories, Willowdale, Ontario, Canada) (n = 4), mean BFU‐E were 145.25 ± 103.3 in autologous serum and 31.0 ± 56.75 in AB serum (p = 0.04). As controls, erythroid progenitors from two normal donors yielded 69 and 61 BFU‐E colonies in autologous serum and 103 and 42 in AB serum; the corresponding CFU‐E were 52 and 235 versus 136 and 137. To confirm that the enhanced erythroid growth in the serum of the patients was attributable to elevated levels of BPA, 5% phytohemagglutinin leucocyte conditioned medium (PHA‐LCM) as a source of this material was used to optimize BFU‐E growth in both patient and AB serum. Mean percentage BPA in the respective sera was estimated as 71.9 ± 36.7 and 12.5 ± 22. It is concluded that an erythroid enhancing factor that shares functional properties with BPA is present in the serum of patients with CRF undergoing long‐term hemodialysis.