Figure 1.

Tubular injury. (a) Day 10 biopsy (D10Bx) tubular epithelium with marked cytoplasmic vacuolization, blebbing, loss of brush border, and spotty cell dropout. The peritubular capillaries (PTC) show endothelial cell changes, including nuclear enlargement and protrusion into the lumen. There is also perivascular and luminal accumulation of mononuclear cells (arrow). Also see Supplementary Figure S2D. (b) Day 84 biopsy (D84Bx) tubular epithelium with diffuse cell injury, cytoplasmic swelling, vacuolization, and blebbing. There is loss of cell polarity, irregular simplification, and loss of brush border admixed with marked reparative changes (center and right). Abnormal PTC endothelial cell lining (arrows) with nuclear enlargement and hyperchromasia. Also see Supplementary Figure S2D. (c) D10Bx electron micrograph of tubule with severe tubular epithelial cell injury with cell sloughing and denudation of the basement membrane. The nuclei appear pyknotic and the cytoplasm severely vacuolated. Fragments of membranes appear in the lumen (arrow). (d) D84Bx, cytoplasmic dissolution and widespread densities consistent with damaged phospholipids suggestive of oxidative membrane injury (arrowheads). The mitochondria appear mostly condensed. (e) D10Bx, disintegration of the brush border and extensive cytoplasmic vesiculation. The mitochondria appear markedly swollen or condensed, with clusters of small mitochondria (mitospheres) (arrow). Bars: (a) and (b) = 25 μm, (c) = 3 μm, (d) and (e) = 2 μm.