Should low‐dose methotrexate therapy be prescribed to dialysis patients?

Methotrexate for rheumatoid arthritis patients who are on hemodialysis

“…Methods to try to eliminate MTX included hemoperfusion, hemodialysis, and plasmapheresis. What was certain from these studies is that even low doses of MTX such as 2.5 mg, if not fatal in this cohort can cause severe pancytopenia for several weeks with placement in a sterile room as even the immunosuppression of low-dose MTX can lead to opportunistic infection [10,11].…”

“…Whether it is affective in altering clinical outcome remains uncertain as only 4 patients have undergone HD treatment for MTX toxicity with 2 surviving and 2 dying [10]. The difficulty of MTX removal by dialysis is owed to the fact that MTX undergoes polyglutamination, which alters the spectrum of the enzyme inhibition by the drug and causes retention of the polyglutamated metabolites of MTX within the cell, and all but one of these are less effective than MTX as an inhibitor of dihydrofolate reductase [12][13][14].…”

Efficacy and safety of tacrolimus treatment for rheumatoid arthritis patients undergoing hemodialysis

“…MTX is not recommended in patients with creatinine clearance \10 ml/min because MTX is primarily cleared by the kidney and up to 90% of the dose is excreted in urine as an unchanged form [1]. Bressolle et al suggested that individual testing is required rather than a general decrease of the MTX dose based only on creatinine clearance [12].…”

“…Bressolle et al suggested that individual testing is required rather than a general decrease of the MTX dose based only on creatinine clearance [12]. Regarding dialysis, hemodialysis clearance of MTX using high-flux membranes has been previously reported to be 92.1± 10.3 ml/min [13], although peritoneal dialysis, conventional hemodialysis, hemoperfusion, and plasmapheresis are reported to be ineffective for MTX intoxication [1]. Besides, there have been several cases of life-threatening pancytopenia caused by low-dose MTX therapy in RA patients undergoing hemodialysis.…”

“…MTX is cleared primarily by the kidney and has been associated with lethal complications in RA patients on hemodialysis even at very low doses [1]. Whether MTX can be administered to patients with renal failure undergoing hemodialysis has not been adequately addressed.…”