Forbes MS, Thornhill BA, Minor JJ, Gordon KA, Galarreta CI, Chevalier RL. Fight-or-flight: murine unilateral ureteral obstruction causes extensive proximal tubular degeneration, collecting duct dilatation, and minimal fibrosis. Unilateral ureteral obstruction (UUO) is the most widely used animal model of progressive renal disease. Although renal interstitial fibrosis is commonly used as an end point, recent studies reveal that obstructive injury to the glomerulotubular junction leads to the formation of atubular glomeruli. To quantitate the effects of UUO on the remainder of the nephron, renal tubular and interstitial responses were characterized in mice 7 and 14 days after UUO or sham operation under anesthesia. Fractional proximal tubular mass, cell proliferation, and cell death were measured by morphometry. Superoxide formation was identified by nitro blue tetrazolium, and oxidant injury was localized by 4-hydroxynonenol and 8-hydroxydeoxyguanosine. Fractional areas of renal vasculature, interstitial collagen, ␣-smooth muscle actin, and fibronectin were also measured. After 14 days of UUO, the obstructed kidney loses 19% of parenchymal mass, with a 65% reduction in proximal tubular mass. Superoxide formation is localized to proximal tubules, which undergo oxidant injury, apoptosis, necrosis, and autophagy, with widespread mitochondrial loss, resulting in tubular collapse. In contrast, mitosis and apoptosis increase in dilated collecting ducts, which remain patent through epithelial cell remodeling. Relative vascular volume fraction does not change, and interstitial matrix components do not exceed 15% of total volume fraction of the obstructed kidney. These unique proximal and distal nephron cellular responses reflect differential "fight-or-flight" responses to obstructive injury and provide earlier indexes of renal injury than do interstitial compartment responses. Therapies to prevent or retard progression of renal disease should include targeting proximal tubule injury as well as interstitial fibrosis. apoptosis; fibrosis; oxidant injury; chronic kidney disease CHRONIC RENAL DISEASE, regardless of etiology, leads ultimately to nephron loss and renal fibrosis. The model of murine unilateral ureteral obstruction (UUO) has been widely employed to study the underlying mechanisms of progressive chronic kidney disease, most focusing on interstitial fibrosis as the final common pathway (43). Extensive formation of atubular glomeruli in this model was revealed by loss of Lotus tetragonolobus lectin binding from cells forming Bowman's capsule as well as from cells of the glomerulotubular junction (14). Through a process of epithelial cell phenotypic transition and remodeling, the urinary pole of Bowman's capsule is sealed off from the atrophic proximal tubular segment (14). To determine the temporal evolution of the lesions in the entire nephron, the present study was undertaken to examine the segmental renal tubular responses following 7 and 14 days of UUO. The results reveal segment-specific responses to UUO that c...

Hair loss is a very common complaint. Patients may describe increased shedding and diffuse or localized alopecia. The differential diagnosis of hair loss includes a number of disorders causing cicatricial or noncicatricial alopecias. This paper describes the clinical approaches and diagnostic tests that are useful in the evaluation of patients presenting with alopecia. It also reviews treatments for noncicatricial alopecias, including androgenetic alopecia, alopecia areata, and telogen effluvium, as well as cicatricial alopecias, including lichen planopilaris, its clinical variant frontal fibrosing alopecia, and discoid lupus erythematosus.

Trachyonychia or rough nails, may present as an idiopathic disorder of the nails or it can be associated with other dermatological conditions. The dystrophic nail findings seen in trachyonychia are characterized by brittle, thin nails, with excessive longitudinal ridging. The most common histopathologic features associated with trachyonychia are spongiosis and exocytosis of inflammatory cells into the nail epithelia; typical features of lichen planus or psoriasis can also be detected. Determining the cause of trachyonychia is challenging. Treatment is often unsatisfactory, although in general it should be aimed at the underlying cause, if found. In most cases, the nail abnormalities improve spontaneously.

Unilateral ureteral obstruction (UUO) in the adult mouse is the most widely used model of progressive renal disease: the proximal tubule is the nephron segment most severely affected and atubular glomeruli are formed after only 7 days of UUO. To determine the proximal nephron response to UUO in the maturing kidney, neonatal mice were examined 7 to 28 days following complete UUO under general anesthesia. Proximal tubular mass and maturation were determined by staining with Lotus tetragolonobus lectin. Superoxide was localized by nitroblue tetrazolium and collagen by Sirius red. Cell proliferation, cell death, PAX-2, megalin, α-smooth muscle actin (α-SMA), renin, and fibronectin were identified by immunohistochemistry. During the first 14 days of ipsilateral UUO, despite oxidative stress (4-hydroxynonenal staining), glomerulotubular continuity was maintained and mitochondrial superoxide production persisted. However, from 14 to 28 days, papillary growth was impaired and proximal tubules collapsed with increased apoptosis, autophagy, mitochondrial loss, and formation of atubular glomeruli. Fibronectin, α-SMA, and collagen increased in the obstructed kidney. Oxidative stress was present also in the contralateral kidney: renin was decreased, glomerulotubular maturation and papillary growth were delayed, followed by increased cortical and medullary growth. We conclude that neonatal UUO initially delays renal maturation and results in oxidative stress in both kidneys. In contrast to the adult, proximal tubular injury in the neonatal obstructed kidney is delayed at 14 days, followed only later by the formation of atubular glomeruli. Antioxidant therapies directed at proximal tubular mitochondria during early renal maturation may slow progression of congenital obstructive nephropathy.

Most pediatric nephrologists prohibit contact/collision sports participation by athletes with a single kidney, particularly football. The available evidence suggests that cycling is far more likely to cause kidney injury. In addition, kidney injury from sports is much less common than catastrophic brain, spinal cord, or cardiac injury. Restricting participation of patients with a single, normal kidney from contact/collision sports is unwarranted.

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We describe a 64-year-old man with past chronic myeloid leukemia. Palisading neutrophilic granulomatous dermatitis of the hands was diagnosed and related to recent allopurinol intake. Allopurinol is known to rarely cause granulomatous reactions, but this appears to be the first case of palisading neutrophilic granulomatous dermatitis induction. Possible mechanisms include immune complex deposition, an immune response directed against the metabolites of allopurinol, or allopurinol hypersensitivity exclusively localized to the skin.

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