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Clin Chim Acta ; 487: 1-5, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30205081

RESUMO

BACKGROUND: High-dose methotrexate (HDMTX) therapy is a key component of many chemotherapy protocols. However, some patients develop HDMTX-induced nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in patients with nephrotoxicity and delayed elimination. Despite the frequency of HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are rarely identified by conventional chemical methods. OBJECTIVE: To determine the composition of crystalluria in a patient with osteosarcoma who was treated with CPDG2. METHODS: Crystalluria was evaluated by optical microscopy, and chemical identification was performed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Orbitrap™ high-resolution mass spectrometry (HRMS). RESULTS: The HRMS spectra of the patient's urine sediment showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA [(C15H15O2N7) + H+]. The FT-IR spectral patterns of the sediment and DAMPA were not identical. SEM was unable to identify the crystal. CONCLUSION: DAMPA crystalluria was identified by Orbitrap™ HRMS in a patient treated with CPDG2 after HDMTX nephrotoxicity. This case reinforces the need to implement adequate measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity, urine sediment analysis should be requested.


Assuntos
Rim/efeitos dos fármacos , Metotrexato/análogos & derivados , Metotrexato/efeitos adversos , Osteossarcoma/metabolismo , gama-Glutamil Hidrolase/metabolismo , Adulto , Feminino , Humanos , Hidrólise , Rim/metabolismo , Rim/patologia , Metotrexato/química , Metotrexato/metabolismo , Metotrexato/uso terapêutico , Metotrexato/urina , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Tamanho da Partícula , Propriedades de Superfície , gama-Glutamil Hidrolase/fisiologia
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