Complement activated leucopenia during hemodialysis: effect of pulse methyl-prednisolone.
We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was withheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97-27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 micrograms/ml +/- SEM 33) and in patients off dialysis (177 micrograms/ml +/- 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.
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Centro di Fisiologia Clinica del Consiglio Nazionale delle Ricerche, Reggio Calabria, Italy.
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D058186:Acute Kidney Injury / Q000097:blood / Q000276:immunology / Q000628:therapy; D002449:Cell Aggregation / Q000187:drug effects; D003167:Complement Activation; D015936:Complement C5a / Q000032:analysis; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000097:blood* / Q000209:etiology / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D006435:Renal Dialysis / Q000009:adverse effects*
D015936:Complement C5a; D008775:Methylprednisolone