Poloxamer 188 vs Placebo for Painful Vaso-occlusive Episodes in Children and Adults With Sickle Cell Disease/Poloxamer 188 vs Placebo for Painful Vaso-occlusive Episodes in Children and Adults With Sickle Cell Disease/Poloxamer 188 vs Placebo for Painful Vaso-occlusive Episodes in Children and Adults With Sickle Cell Disease-Reply

The EPIC study investigators were aware of the prior cardiac studies cited by Drs Kenter and Cohen suggesting nephrotoxicity due to poloxamer 188. It is important to note that these early studies used commercial-grade poloxamer 188. Subsequent studies showed that removal of impurities from this preparation reduced nephrotoxicity in a rat model and that the isolated impurities caused nephrotoxity. A phase 1 study of the resulting purified poloxamer 188 for acute chest syndrome in 43 participants with SCD focused on safety and included studies of urinary N-acetylglucosaminidase, retinol-binding protein, creatinine and creatinine clearance, albumin, and IgG excretion; participants were followed up for up to 10 days with repeat measurements at 28 to 35 days. The investigators concluded that there were no time-related increases in serum creatinine or creatinine clearance and no evidence of adverse effects on glomerular integrity, permeability, filtration, or proximal or distal tubular function. Phase 2 and 3 studies of purified poloxamer 188 for vaso-occlusive episodes in SCD also showed no evidence of nephrotoxicity based on serum creatinine levels. The effects of poloxamer 188 on the kidney are more fully explained in Supplement 3 of our article.