TGF-beta1 is a key mediator that regulates, in a dose-dependent fashion, transdifferentiation of tubular epithelial cells into alpha-SMA+ myofibroblasts. This transdifferentiation is markedly enhanced by growth on collagen type I. These findings have identified a novel pathway that may contribute to renal fibrosis associated with overexpression of TGF-beta1 within the diseased kidney.

Macrophages accumulate within glomeruli and the interstitium in diabetic nephropathy and the intensity of the interstitial infiltrate is proportional to the rate of subsequent decline in renal function. These human data support animal studies that suggest a pathogenic role for the macrophage in diabetic nephropathy.

More than 50% of patients with non-Shiga toxin-associated hemolytic uremic syndrome (non-Stx-HUS) progress to ESRD. Kidney transplant failure for disease recurrence is common; hence, whether renal transplantation is appropriate in this clinical setting remains a debated issue. The aim of this study was to identify possible prognostic factors for renal transplant outcome by focusing on specific genetic abnormalities associated with the disease. All articles in literature that describe renal transplant outcome in patients with ESRD secondary to non-Stx-HUS, genotyped for CFH, MCP, and IF mutations, were reviewed, and data of patients who were referred to the International Registry of Recurrent and Familial HUS/TTP and data from the Newcastle cohort were examined. This study confirmed that the overall outcome of kidney transplantation in patients with non-Stx-HUS is poor, with disease recurring in 60% of patients, 91.6% of whom developed graft failure. No clinical prognostic factor that could identify patients who were at high risk for graft failure was found. The presence of a factor H (CFH) mutation was associated with a high incidence of graft failure (77.8 versus 54.9% in patients without CFH mutation). Similar results were seen in patients with a factor I (IF) mutation. In contrast, graft outcome was favorable in all patients who carried a membrane co-factor protein (MCP) mutation. Patients with non-Stx-HUS should undergo genotyping before renal transplantation to help predict the risk for graft failure. It is debatable whether a kidney transplant should be recommended for patients with CFH or IF mutation. Reasonably, patients with an MCP mutation can undergo a kidney transplant without risk for recurrence.

IntroductionMammographic density (MD), after adjustment for a women’s age and body mass index, is a strong and independent risk factor for breast cancer (BC). Although the BC risk attributable to increased MD is significant in healthy women, the biological basis of high mammographic density (HMD) causation and how it raises BC risk remain elusive. We assessed the histological and immunohistochemical differences between matched HMD and low mammographic density (LMD) breast tissues from healthy women to define which cell features may mediate the increased MD and MD-associated BC risk.MethodsTissues were obtained between 2008 and 2013 from 41 women undergoing prophylactic mastectomy because of their high BC risk profile. Tissue slices resected from the mastectomy specimens were X-rayed, then HMD and LMD regions were dissected based on radiological appearance. The histological composition, aromatase immunoreactivity, hormone receptor status and proliferation status were assessed, as were collagen amount and orientation, epithelial subsets and immune cell status.ResultsHMD tissue had a significantly greater proportion of stroma, collagen and epithelium, as well as less fat, than LMD tissue did. Second harmonic generation imaging demonstrated more organised stromal collagen in HMD tissues than in LMD tissues. There was significantly more aromatase immunoreactivity in both the stromal and glandular regions of HMD tissues than in those regions of LMD tissues, although no significant differences in levels of oestrogen receptor, progesterone receptor or Ki-67 expression were detected. The number of macrophages within the epithelium or stroma did not change; however, HMD stroma exhibited less CD206+ alternatively activated macrophages. Epithelial cell maturation was not altered in HMD samples, and no evidence of epithelial–mesenchymal transition was seen; however, there was a significant increase in vimentin+/CD45+ immune cells within the epithelial layer in HMD tissues.ConclusionsWe confirmed increased proportions of stroma and epithelium, increased aromatase activity and no changes in hormone receptor or Ki-67 marker status in HMD tissue. The HMD region showed increased collagen deposition and organisation as well as decreased alternatively activated macrophages in the stroma. The HMD epithelium may be a site for local inflammation, as we observed a significant increase in CD45+/vimentin+ immune cells in this area.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0592-1) contains supplementary material, which is available to authorized users.

This is the first study demonstrating the protective effect of ascorbic acid against colistin-induced nephrotoxicity and tubular apoptosis. Co-administration of ascorbic acid has the potential to increase the therapeutic index of colistin.

The amelioration of the pathological findings of experimental mesangial proliferative glomerulonephritis by blockade of PDGF receptor activity suggests the potential clinical utility of this approach as a therapeutic strategy in glomerular disease.

Renal primary cilia are sensory antennas required for the maintenance of normal epithelial differentiation and proliferation in the kidney, but they also have a potential role in epithelial differentiation during renal injury and repair. In mice, tubular damage causes an increase in the length of renal cilia, which may modify their sensory sensitivity during repair. Here, we investigated whether the alteration of renal cilium length during renal injury is clinically relevant. Using biopsies of human renal transplants that suffered acute tubular necrosis during transplantation, we compared the length of renal primary cilia with renal function. Serial biopsies showed that acute tubular necrosis resulted in more than a doubling of cilium length throughout the nephron and collecting duct approximately 1 wk after injury. Allografts displayed a trend toward normalization of cilium length in later biopsies, and this correlated with functional recovery. A mouse model of renal ischemia-reperfusion confirmed the increase and subsequent regression of cilium length during renal repair, displaying complete normalization of cilium length within 6 wk of injury. These findings demonstrate that the length of renal cilia is a clinically relevant indicator of renal injury and repair.

Abstract. The p38 mitogen-activated protein kinase (MAPK) pathway is a pro-inflammatory signal transduction pathway.