Concept Map: Methotrexate Renal Toxicity

 

Picture created using biorender.com
Pathology pic obtained from google: Arkana lab collection. 

FDA Approves Glucarpidase to Reduce Toxic Levels of Methotrexate

"The FDA has approved glucarpidase (marketed as Voraxaze) to lower toxic levels of methotrexate related to kidney failure. Cancer patients may develop kidney failure when treated with high doses of methotrexate. In a study of 22 patients receiving glucarpidase, 10 patients had methotrexate levels fall below a critical level within 15 minutes and stay low for 8 days. The drug eliminated 95% of methotrexate in all patients."

This should be a resourceful drug for our patients; especially those who receive intrathecall/IV MTX and get kidney injury where we often have to do dialysis due to the toxic levels; so potentially saving patients from dialysis and it's complications.

TOPIC DISCUSSION: Methotrexate in the urine

Methotrexate can cause renal damage is well known but precipitation in the urine and appearance in urine analysis is unique.  Tubular obstruction damage and urine precipitation noted in a recent picture in Kidney International highlights this toxicity.  Check it out below

Ref:
http://www.nature.com/ki/journal/v80/n2/abs/ki201197a.html

CLINICAL CASE 38, ANSWERS AND SUMMARY

Which of these options are treatment options for management of methotrexate nephrotoxicity?

GI decontamination	4 (14%)
Aggresive hydration	8 (28%)
Urinary Alkalinization	14 (50%)
Leucovorin( IV)	13 (46%)
Leucovorin (PO)	5 (17%)
CPDG glucarpidase	3 (10%)
Recurrent intermittent Hemodialysis	4 (14%)
Continuous venovenous dialysis	3 (10%)

MTX ( methotrexate) is a chemo agent that is nephrotoxic.  At high doses, it and its metabolite can accumulate and can cause acute tubular injury.  Dosages higher than 1000mg/m2 are what is associated with renal damage. Most oncologists use prevention strategies with hydration and leucovorin to help combat this side effect.
What helps decrease MTX levels:- all the above listed are right answers. The glucarpidase is a new agent that is experimental but has shown some promise.  

For more information, see:

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/21531323

http://www.ncbi.nlm.nih.gov/pubmed/21146122

http://www.ncbi.nlm.nih.gov/pubmed/20679598