minocycline and Ureteral-Obstruction

Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2⁺/⁺) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2⁻/⁻) and MMP-2⁺/⁺ mice treated with minocycline (inhibitor of MMPs). In MMP-2⁺/⁺ mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, α-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-β1, Smad, Wnt, β-catenin, and Snail). In contrast, the kidneys of MMP-2⁻/⁻ mice and minocycline-treated MMP-2⁺/⁺ mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis.

Topics: Animals; Collagen; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Histocytochemistry; Kidney Diseases; Kidney Tubules; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Transgenic; Minocycline; Phenotype; RNA, Messenger; S100 Calcium-Binding Protein A4; S100 Proteins; Ureteral Obstruction

A 63-year-old man who had undergone Miles' operation for rectal cancer in another hospital was referred due to a high fever and renal failure. Abdominal computed tomographic (CT) scan revealed metastatic liver tumor, paraaortic lymph node swelling, bilateral hydronephrosis and a left simple renal cyst located at the lower pole. Bilateral ureteral stenting was undertaken for relieving ureteral obstruction. Serum creatinine and high fever improved immediately. However, at 11 days after the ureteral stenting the high fever recurred. CT scan and ultrasonography revealed persistent left hydronephrosis and a change of left simple renal cyst into infected cyst. After an exchange of left ureteral stent and percutaneous pus drainage from the left infected renal cyst, high fever declined immediately. A review of the literature suggests that this is the 100th case report of infected renal cyst in Japan. We discuss the clinical features, etiology, imaging study and treatment of infected renal cyst.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Hydronephrosis; Kidney Diseases, Cystic; Male; Middle Aged; Minocycline; Radiography, Abdominal; Tomography, X-Ray Computed; Ultrasonography; Ureteral Obstruction