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Methotrexate-Induced Crystal Nephropathy

Michael Kuperman, MD renal pathologist at arkana laboratories
By Michael Kuperman, MD

Aug 13, 2019

Methotrexate-induced acute kidney injury, Methotrexate-Induced Crystal Nephropathy, teaching points, Arkana Laboratories

The patient is a 50-year-old male who presents with a creatinine of 4.2 mg/dL (baseline 1.0 mg/dL). He has been receiving high dose methotrexate for treatment of osteosarcoma. Image 1 shows a normal glomerulus. Image 2 shows moderate interstitial fibrosis. Image 3, 4, and 5 shows polarizable silver-positive crystals within the tubular lumens. This is a case of methotrexate-induced crystal nephropathy.

Methotrexate-induced crystal nephropathy is characterized by acute tubular injury with scattered intratubular and interstitial needle-shaped, golden-brown crystals which are frequently arranged in annular structures. The crystals show birefringence under polarized light and are methenamine silver positive.  Methotrexate-induced crystal nephropathy is believed to be an under-recognized entity. It has been reported in the absence of toxic methotrexate levels and the crystals can also be seen in the urine. Methotrexate-induced acute kidney injury is usually reversible and treatment is directed at volume repletion and alkalization of the urine.


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