The cellular and molecular mechanisms of cold storage‐ATN are not well characterized. In our earlier studies, cold storage caused necrosis of human proximal tubular epithelial (RPTE) cells, whereas apoptosis was prominent during rewarming. An intriguing finding was the pronounced swelling of the mitochondria in the cold, which promoted us to further characterize its role in rewarming‐associated apoptosis. Human proximal tubular epithelial cells were cold stored in University of Wisconsin (UW) solution for 48 h followed by 24 h of rewarming in regular cell culture medium. During the cold storage, there was no significant change in the Bcl‐2 to Bax protein ratio, mitochondrial location of cytochrome C or caspse‐3 activity. However, during rewarming, the Bcl‐2 to Bax ratio increased, cytochrome C was translocated to cytosol, and caspase‐3 was activated: events and timing were consistent with the occurrence of apoptosis during rewarming. In a time‐course experiment, mitochondrial swelling was discernable by electron microscopy as early as at 2 h. Cold storage of isolated‐mitochondria for 2 h was attended by an increase in the opening of the permeability transition pores (PTP), suggesting PTP opening as an early mechanism for mitochondrial swelling. Addition of antioxidants (deferoxamine or 2‐methyaminochroman) to the storage solution suppressed mitochondrial pore opening and swelling, Bcl‐2 to Bax ratio increase, cytochrome C translocation, caspase‐3 activation as well as rewarming‐induced apoptosis. Our data demonstrate for the first time that apoptosis following cold storage and rewarming of human renal tubular cells is accompanied by specific mitochondrial events, and that these events and apoptosis can be suppressed by adding antioxidants to the cold storage solution.

Weight gain is associated with an expanded renal medullary interstitium in humans and in animal models of obesity. In this study, the consequence of obesity and this expanded matrix on renal papillary structure was examined in 15 obese rabbits fed a high fat diet for 8-12 weeks compared to 21 rabbits fed a standard diet. When examined under a dissecting microscope, the tips of the renal papillae from formalin-fixed, methylene blue-stained kidneys showed patent ducts of Bellini in 5 of 5 instances from 2 lean rabbits, but in only 2 out of 12 ducts from 3 obese rabbits. The ostia of the remaining ducts were significantly distended (205 +/- 42 microns versus 56 +/- 8 microns) and occupied by lightly staining granular material. When examined with scanning electron microscopy, all ducts were patent in lean rabbits (6 ducts in 4 rabbits, averaging 104 +/- 12 microns across), whereas only 6 of 11 ducts were patent in papillae from 4 obese rabbits. Renal medullary parenchymal tissue appeared at the openings of the remaining 5 ducts of Bellini in the 4 rabbits. Not only were these 5 ducts significantly distended by the interstitial material (with openings averaging 248 +/- 56 microns across), but the associated collecting ducts were dilated relative to control (100 +/- 15 microns versus 75 +/- 7 microns). Since the ducts of Bellini are the only renal openings that are not corsetted by a fibrous capsule, the authors speculate that the expanded medullary interstitium and increased renal sinus lipid partially obstruct renal outflow and elevate renal interstitial hydrostatic pressure in obesity, causing a prolapse of parenchymal contents, further obstructing urine outflow and leading to distention of the collecting ducts and ducts of Bellini.

No abstract

Propylthiouracil (6-propyl-2-thiouracil), an anti-thyroid agent, was fed to mice in a concentration equal to 0.1% of their diet for periods of 10 and 15 weeks. The cells of the inner zone of the adrenal cortex were examined with the electron microscope. In animals receiving propylthiouracil for ten weeks mitochondria were altered and the smooth endoplasmic reticulum (SER) showed a marked focal proliferation. In contrast to control animals rough endoplasmic reticulum was abundant and was frequently associated with the hyperplastic SER. After 15 weeks these alterations were no longer present but had been replaced by a spectrum of "brown degeneration." The less affected cells were characterized by increased numbers of liposomes and lysosomes and the more affected cells by liposomal and mitochondrial degeneration. These observations emphasize that "brown degeneration" is a true degenerative process and not a spontaneous proliferation of ceroid pigment. It is suggested that the changes described may be directly related to an alteration in cholesterol metabolism.