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Gail Randall, Jill Meyer, Charles Swanepoel, Peter Jacobs, Burst-promoting activity in the serum of patients with chronic renal failure undergoing long-term hemodialysis, Stem Cells, Volume 11, Issue 5, 1993, Pages 428–434, https://doi.org/10.1002/stem.5530110510
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Abstract
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.
