Schwere renale Methotrexat-Ausscheidungsstörung nach Hochdosis-Therapie

Abstract

Even in patients with normal renal function, high-dose methotrexate therapy (HDMTX) may be followed by extremely prolonged MTX elimination through alkaline diuresis is performed correctly. By inquiry in Germany, Austria and Switzerland for HDMTX infusions with MTX plasma concentration 42 h after start of exposure (MTX-42) higher than 5 mumol/l (microM), we analyzed data from 21 patients in whom impairment of renal methotrexate elimination had received 5 g/m2.24h, 3 had received 12 g/m2.4h. They presented with MTX-48 serum level between 1.7 and 1404 microM. There was no recognizable causative factor. As early signs for impaired elimination, we identified enhanced vomiting during MTX infusion in 8/21, elevated steady-state-MTX in 11/15, and a rise of serum creatinine greater than 50% in 14/16 patients in whom respective data were available. Creatinine rose to a maximum of 1.0-4.9 mg/dl within 1-4 days in 19/21 patients (accompanied by diuresis problems in only 5 patients) and normalized within 3-17 days in all but two patients. Creatinine maximum correlated weakly with MTX-48 (r = 0.34) and with extrarenal toxicity. 8 patients had normal (WHO 0-II degree), 8 other had intensified (III-IV degrees) but not critical extrarenal MTX toxicity with calcium folinate (CF) doses of 0.2-1.6 mg/kg.microM MTX q 6 h started 28-54 h after beginning of MTX exposure. 5 patients had unusual toxicity. 2 patients suffered from severe but reversible encephalopathies with CF doses of 0.05 and 1 mg/kg.microM MTX q 6 h started after 51 and 36 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

High‐dose methotrexate‐induced nephrotoxicity in patients with osteosarcoma

“…14 However, reports of significant morbidity and mortality secondary to HDMTX-induced renal dysfunction have continued to appear in the literature. 11,[15][16][17][18][19] Because there is no centralized reporting mechanism for MTX nephrotoxicity, to our knowledge the current incidence of HDMTX-induced renal dysfunction is unknown.…”

Two Pediatric Osteosarcoma Cases with Delayed Methotrexate Excretion: Its Clinical Course and Management

“…The excretion of MTX is influenced by many factors such as age, the hydration status and the concurrent use of nephrotoxic agents [2]. Furthermore, it has been reported that delayed MTX excretion may occur in the absence of any predisposing factor [5,10,11], and in our cases, the reason for delayed MTX excretion was not determined. However, we surmise that a young age or a small body size might have contributed to its development.…”

“…However, the factors that predisposed the patients to delayed MTX excretion were unclear in these cases. A reduced effective blood volume or the concurrent use of nephrotoxic agents are known to be related to the development of delayed MTX excretion [5,6], but neither patient had signs of decreased blood volume nor they were concurrently receiving any nephrotoxic agent [7]. Furthermore, the previous courses of HD MTX in case 2 and the following chemotherapy (case 1) were uneventful.…”

Methotrexate Side Effects: Review Article

“…It consists frequently on a nonoliguric renal failure which generally disappears in two to three weeks [12][13][14]. Some patients may develop nausea, vomiting or diarrhea as prodroms [14,15]. Urine alkalinization and leucoverin rescue are the cornerstones of the management of the earlier signs of renal dysfunction.…”