Nephrotoxicity induced by drugs: The case of foscarnet and atazanavir-A SEM and μFTIR investigation

Biopsies of native or transplanted kidneys in patients suffering chronic or acute renal failure are commonly stained for tissue examination and search for possible crystal deposits which are then identified by polarizing microscopy and staining by von Kossa's method revealing mainly calcium deposits. Renal biopsies presumably containing crystal deposits were analyzed with a Spotlight 400 μFTIR (Fourier Transform Infra Red) imaging system in the mid-infrared spectral range to obtain infrared maps of tissue slides at high spatial resolution, down to 10 microns. When required, an optional ATR imaging accessory was used, improving the spatial resolution by a factor four, down to 3 microns at 1000 cm−1. Among the 685 renal biopsies, 72% contained abnormal non-proteic material. Among them, 2.16% contained drug crystals (triamterene, N-acetylsulfadiazine, ciprofloxacine, indinavir, atazanavir, foscarnet, and vancomycine). We focused on foscarnet and atazanavir deposits. In the case of foscarnet-induced renal failure, two types of crystals were found in one patient. They were located in different parts of the nephron: sodium and/or calcium phosphonoformate crystals within glomerules and carbapatite in the proximal tubular cells. By contrast, atazanavir was only found in the tubular lumen of the nephron.A precise identification of crystal deposits is essential for the diagnosis of an unexplained renal failure. Common histological procedures clearly fail to identify crystals deposits accurately. In most cases, light and polarizing microscopic examination should be completed by FTIR analysis.