case_images: PMC11829840_01
case_images: Kidney biopsy findings. PAS staining (A), PAM staining (B), AZAN staining (C) and dark-field microscopy (D) show granular particles (arrows) and immunostaining of the proximal tubular marker CD10 (E), with proximal tubular cells showing degeneration, detachment or flattened morphology (stars). Mitochondrial production of reactive oxygen species (F). Scale bars = 50 mum
case_images: 795_2024_411_Fig1_HTML.jpg
case_images: PMC11829840_01_795_2024_411_Fig1_HTML.jpg
case_images: Fig1
case_images: Renal biopsy revealed acute tubular necrosis (ATN) with tubular cells showing degeneration, detachment or flattened morphology (Fig. 1A-C), and immunostaining for CD10 indicated that the damaged tubules were proximal tubules (Fig. 1E). Azan staining revealed white birefringent granular materials within the cells and lumen of the proximal tubules under dark-field microscopy (Fig. 1C, D). These nanoparticles may contribute to proximal tubular damage and increase mitochondrial ROS production (Fig. 1F), which can lead to ATN.
case_images: Transmission electron microscopy image of a renal biopsy sample showing the glomerulus (A, F) and proximal tubules (B-E). Arrow heads indicate nanoparticles. Magnification at x 1000 (B), x 4000 (A, C), x 20,000 (F), and x 40,000 (D, E)
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case_images: PMC11829840_01_795_2024_411_Fig2_HTML.jpg
case_images: Fig2
case_images: Electron microscopy revealed subendothelial space expansion, indicating glomerular endothelial damage (Fig. 2A), and vacuolar degeneration of the proximal tubule, with mitochondrial damage (Fig. 2B, C). Interestingly, 10-20 nm black granules and 100 nm vesicles were identified within the lysosomes and tubular lumen (Fig. 2D, E) as well as under the glomerular basement membrane (Fig. 2F).
case_images: Urinary analysis with SDS-polyacrylamide gel electrophoresis (PAGE) (A) and elemental analysis (B-E). SDS-PAGE of urinary proteins from patients with CP-induced Fanconi syndrome or IgA nephropathy at biopsy and 4 months later as well as the supernatant of powdered CP tablets dissolved in water (A). LVSEM images of the urine samples of patients with CP (B) and IgA nephropathy (C), elemental analysis of the urine of CP patient indicating Si with green dots and O with purple dots (D), and their mass concentrations (E)
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case_images: PMC11829840_01_795_2024_411_Fig3_HTML.jpg
case_images: Fig3
case_images: Analysis of powdered CP tablets. Light microscopy image (A) with dark-field illumination (B) x 400. Elemental analysis with LVSEM-EDS indicated blue dots for Si and green dots for O (C, D). Transmission electron micrographs of powdered CP tablets with particle sizes of 10-20 nm (E, F)
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case_images: PMC11829840_01_795_2024_411_Fig4_HTML.jpg
case_images: Fig4
case_images: The powdered CP tablet was poorly dissolved in water, and in addition to the orange-colored vesicles with a size of 100-200 nm, smaller fine particles that emitted white polarized light were observed in the supernatant (Fig. 4A, B). Elemental analysis via low-vacuum scanning electron microscopy (LVSEM) equipped with energy dispersive X-ray spectroscopy (EDS) revealed that the lumpy CP powder contained unevenly distributed Si in addition to C and O (Fig. 4C, D). The granule size of the CP tablets was 10-20 nm (Fig. 4E, F), which was approximately the same size as the black granules observed in the proximal tubules.