Comparison of Hemodialysis versus Hemoperfusion in the Clearance of High‐Dose Methotrexate in Pigs

Abstract

To evaluate the different capabilities of hemo-perfusion (HP) and hemodialysis (HD) treatment in resolving the side effects during high-dose methotrexate (MTX) therapy, an experimental comparative study was done. Under general anesthesia, 12 female Large-White pigs, 35 +/- 5 kg body weight, underwent a bilateral renal vessel ligature to create an acute renal failure and avoid the physiologic elimination of MTX. An MTX i.v. infusion was performed using a dose of 12.5 g/m2 and for a specific time according to its pharmacokinetics. The animals were divided into 2 groups of 6 animals each and connected to the extracorporeal circuit; the first group was submitted to a 1-h HP with an anion exchange resin (Dow 1X-2, Dow Chemical) and the second group to 1-h HD with capillary polysulfone fibers (F6, Fresenius). Blood samples were taken at established intervals for hematological and biochemical evaluations. The results demonstrate a higher capability of HP treatment (P < 0.001) related to HD in MTX removal.

Continuous plasma resin perfusion for detoxification of methotrexate

“…Under physiological conditions, MTX is also negatively charged and hydrophilic [3] and this may explain why MTX is also highly eectively adsorbed on the BR-350 column. Moreover, our observation is con®rmed by recent data obtained from pigs demonstrating that haemoperfusion over anionic resins is the most eective method of extracorporeal MTX removal [9]. Therefore, the combined use of PRP and HDF, as well as of PRP alone are eective methods for extracorporeal treatment of MTX toxicity, avoiding the disadvantages of other treatment regimes.…”

Effective removal of methotrexate by high-flux hemodialysis

“…In our experience, HD was superior to HD with charcoal hemoperfusion [18]. In a porcine model, hemoperfusion over an exchange resin slightly outperformed HD via a Fresenius F6 (not high-flux) membrane [19]. Wall et al [11] prospectively administered MTX in patients with chronic dialysis-dependent renal insufficiency and achieved adequate clearance using high-flux HD.…”

Extracorporeal Treatment for Methotrexate Poisoning

“…A total of 1376 articles were identified after removal of duplicates. In the final analysis, 92 articles were included, including two in vitro experiments (174,175), four animal experiments (176 –179), 84 case reports and case series (24,35,88,90,126,163,170,171,180 –255), one pharmacokinetic modeling study (256), and one observational study (160). Although several articles were designed as pharmacokinetic studies in kidney failure patients (170,190,204,225,242), many participants in these studies developed methotrexate-associated toxicity and were included in case reports.…”