Glucarpidase treatment for methotrexate intoxication: a case report and review of the literature.

High-dose methotrexate (MTX) induced acute kidney injury can lead to sustained high systemic MTX levels and severe toxicity. A 39-year-old man with lymphoblastic T-cell lymphoma was admitted to our intensive care unit with elevated serum creatinine and prolonged high serum MTX levels. Standard supportive care was complemented by the addition of a relatively novel agent, glucarpidase, which rapidly lowered the extracellular levels of MTX. Several case series support this effect of glucarpidase, but no randomised controlled trial has been performed to show this leads to better outcome. Furthermore, glucarpidase might negatively affect leucovorin rescue therapy. Lastly, glucarpidase carries a significant financial burden. Based on the current evidence we cannot recommend glucarpidase until further research elucidates its role in the treatment of MTX toxicity. There is no randomised clinical evidence to support its use in severe cases and theoretical evidence suggests that after prolonged exposure to high MTX levels glucarpidase administration is unable to reverse high intracellular MTX. We recommend that new randomised controlled studies be aimed at early administration of glucarpidase in patients with high MTX levels shortly after administration to prevent direct toxic effects of MTX on kidney function and further uptake into cells.

Transient versus persistent acute kidney injury and the diagnostic performance of fractional excretion of urea in critically ill patients.

AIMS: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU. METHODS: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging. RESULTS: Of 150 patients, 51 and 41 patients were classified as having T-AKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49-0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47-0.74, and 0.58; 95% CI: 0.43-0.73, respectively). CONCLUSIONS: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.

Dosing of antimicrobial agents in critically-ill patients with acute kindey injury and continuous venvenous haemofiltration.

OBJECTIVE: To summarize the general guidelines for drug dosing in critically-ill patients with acute kidney injury and continuous venovenous haemofiltration (CVVH), and to discuss whether the predicted dose adjustment is an as reliable estimate than one based on observed data, considering the recent literature. METHODS: Literature search was done in PubMed database for human studies. CONCLUSIONS: In critically-ill patients receiving CVVH, dosing of antibiotics based on the predicted clearances yield rough estimates. Because of interpatient variability observed in the clearance of many antibiotics, monitoring of plasma concentration is highly recommended whenever possible, and especially for those antibiotics that are eliminated predominantly by the kidney, and that have a low therapeutic threshold such as aminoglycosides and glycopeptides, or in patients requiring protracted treatment. However, for many antibiotics, monitoring of blood concentrations is not routinely available and adequate concentrations can only be inferred from clinical response. Therefore, it is important to realize that among many other causes, failure to respond within the first few days of antibiotic treatment may be due to inadequate dosing.