Application of Imaging Techniques to Cases of Drug-Induced Crystal Nephropathy in Preclinical Studies

• DOI: 10.1093/toxsci/kfx044
• Publication Date: 2017-02-17T04:27:25Z
• Authors: Barbara Lenz; Andreas Brink; Monira Siam; Anne De Paepe; Simon Bassett; Anne Eichinger-Ch...; Pierre Maliver; Rachel Neff; Urs Niederhauser; Bernd Steinhuber; Raphael Zurbach; Thomas Singer; Christoph Funk; Franz Schuler; Mudher Albassam; Simone Schadt
• Keywords: 0303 health sciences; Drug-Related Side Effects and Adverse Reactions; Molecular Structure; Spectrophotometry, Infrared; Drug Evaluation, Preclinical; Acute Kidney Injury; Kidney; Spectrum Analysis, Raman; Rats; 3. Good health; Macaca fascicularis; Mice; 03 medical and health sciences; Pharmaceutical Preparations; Species Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Animals; Crystallization

A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and not uncommon in preclinical studies, where high doses are tested. An understanding the nature important for human risk assessment further development. Our aim was investigate ability various imaging techniques detect presence or metabolites crystals. We applied matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) imaging, Raman infrared microspectroscopy, scanning electron microscopy coupled with energy dispersive X-ray (SEM/EDX) spectroscopy standard histopathology cases drug-induced nephropathy, induced rodents primates by 4 compounds. MALDI-FTICR MS enabled identification drug-related content all without reference material accuracy. Crystals were composed unchanged parent drug and/or metabolites. Similar results obtained using microspectroscopy 2 In absence standards metabolites, showed that crystals consisted components similar, but identical, administered other compounds, a limitation these techniques. SEM/EDX which counter ions colocalized identified material, complementing findings. Therefore, we recommend as first-line methodology characterize nephropathies. may be useful when cannot applied. could considered complementary technology.