LAUSR

High-dose methotrexate (MTX) chemotherapy is used to treat a variety of malignancies, including lymphoma, lymphoid leukemia, and sarcomas. Since MTX binds to proteins at a binding ratio of 50%, and nearly 90% of MTX in the blood is excreted via the kidneys, impaired kidney function would cause accumulation of MTX and result in complications. We encountered 4 patients who developed acute renal failure following high-dose MTX administration, but recovered after several modalities of blood purification therapies at our hospital. To clarify which blood purification method might be the most effective to remove accumulated MTX, we retrospectively investigated the removal rate of MTX by different modalities of blood purification therapy. Four patients (3 males and 1 female) who developed acute renal failure immediately after the start of administration of high-dose MTX therapy received blood purification therapies, including hemodialysis (HD), hemodiafiltration (HDF), plasma exchange (HD + PE), direct hemoperfusion (DHP), or any combination of the above, from January 2010 to December 2015. Case 1: Patient (female, 57 years old, weight 54 kg) received HD (9times) followed by HDF (5 times) for 4 h each using a cellulose triacetate (CTA) membrane. Case 2: Patient (male, 56 years old, weight 90.7 kg) received HD (8 times) with 2different membranes (polyethersulfone and polyarylate blended polymer (PEPA); CTA; polymethyl methacrylate (PMMA)) for 4 h each. Case 3: Patient (male, 79 years old, weight 56 kg) received HD (3 times) followed by HDF (6times), HD + PE (once) for 4 h each. Case 4: Patient (male, 23 years old, weight 104.6kg) received HDF using CTA (3 times) membranes, followed by HD + PE, HD + DHP (3 times) and DHP (once) for 4 h each. We retrospectively investigated the blood level of MTX before and after each of the blood purification therapies and compared the removal rate of MTX by the different modalities. The average dose of MTX prescribed was 1.1 g/m2 (0.9-3.8). The blood levels of MTX reduced from 29.4 μM (9.8-57.8) to 0.06 μM (0.02-0.09) after several treatment sessions, and improvement of the renal function was observed in all cases. The highest removal rate was observed with HD + DHP (61.7%, n = 3), followed by DHP (50.0%, n = 1), HDF (44.1%, n = 19), HD (34.6%, n = 23) and HD + PE (30.3%, n = 2). As for the most effective membrane used for HD, the highest removal ratio was observed with PEPA (69.6%, n = 3), followed by PMMA (36.5%, n = 3) and CTA (28.2% %, n = 17). In regard to the most effective modality for removing accumulated MTX from the blood, high removal efficiencies were observed for HD + DHP and DHP. Therefore, it appears that use of these modalities would be the most desirable, as these appear to be highly capable of effectively removing accumulated MTX. Higher removal rates were observed with the use of the PEPA membranes than with that of the CTA and PMMA membrane, probably due to the better adsorption capacities of PEPA membrane. From these results, we conclude that HD or HDF with a high-adsorption characteristics (PEPA) combined with DHP might be the most effective method for removing accumulated MTX from the blood, as well as controlling water removal and correcting electrolyte concentrations. Improvement of the renal function was observed after several sessions of blood purification therapy in all patients who developed acute renal failure after high-dose MTX therapy. The removal efficiency of MTX was sufficiently high when HD + DHP, HDF or HD was performed, especially with the use of a membrane with high adsorption characteristics.