Vittoria Esposito

C/EBP homologous protein (CHOP) is an important mediator of endoplasmic reticulum (ER) stress-induced cell and organ injury. Here we show that lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with ER stress and elevated CHOP. We postulated that CHOP(-/-) mice would be protected against LPS-induced-AKI. Unexpectedly, while Toll-like receptor 4 (TLR4) expression levels were comparable in kidneys of CHOP(-/-) and wild-type (WT) mice, CHOP(-/-) mice developed more severe AKI after LPS injection. Furthermore, the severe kidney injury in CHOP(-/-) mice was associated with an exaggerated inflammatory response. Serum TNF-α levels were more elevated in LPS-treated CHOP(-/-) mice. There was a 3.5-fold higher amount of renal neutrophil infiltrates in LPS-treated CHOP(-/-) than in WT mice. Additionally, the kidneys of LPS-treated CHOP(-/-) mice had a more prominent increase in NF-κB activation and further upregulation of proinflammatory genes, i.e., c-x-c motif ligand 1 (CXCL-1), macrophage inflammatory protein-2 (MIP-2), and IL-6. Finally, proximal tubules, glomeruli, and podocytes isolated from CHOP(-/-) mice also had an exaggerated proinflammatory response to LPS. Since LPS directly increased CHOP in glomeruli and podocytes of WT mice, together these data suggest that the LPS-induced increase of CHOP in kidneys may inhibit inflammatory response in renal cells and provide protection against AKI.

IntroductionPatients on dialysis (HDPs) are a category at high risk from COVID-19 and thus a high-priority group for vaccination. COVID-19 vaccine hesitancy has been a concern since the availability of the first vaccine. The objective of this study was to determine hesitancy rates and factors associated with hesitancy toward COVID-19 vaccination in HDP.MethodsHDP were surveyed with an ad hoc questionnaire in 4 large dialysis facilities in Europe: Le Mans and Paris, in France, and Cagliari and Pavia, in Italy. The questionnaire explored different domains associated with vaccine hesitancy, such as perception of disease severity, sources of information about the vaccine and the disease, and confidence in the health care system.ResultsA total of 417 patients (average age 69 years, 60% men) agreed to answer the questionnaire. Hesitancy was associated with younger age (P = 0.003), lower perception of disease severity (P < 0.001) and vaccine efficacy (P < 0.001), and lower trust in vaccination (P < 0.001) and in the health care system and scientists (P < 0.001) in the univariate analysis. In the multivariate models, concerns about side effects (P = 0.004) and vaccine efficacy (P < 0.001) and living in France (P = 0.04) remained associated with higher vaccine hesitancy, whereas having received an influenza vaccine (P = 0.032) and trusting scientists (P = 0.032) were associated with a more positive attitude toward vaccination.ConclusionsHDPs have a good understanding of the risks associated with COVID-19. Vaccine hesitancy was not associated with educational level, age, or gender but rather with lack of confidence in vaccine efficacy and concerns about safety. HDPs were quite skeptical about the health care system but generally trusted scientists.

BACKGROUND: Recently there has been a progressive loss of specialty related skills for nephrologists. Among the skills we find the kidney biopsy that has a central role in diagnosis of renal parenchymal disease. One of the causes might be the belief that the kidney biopsy should be performed only in larger Centers which can rely on the presence of a renal pathologist and on nephrologists with a large experience. This trend may increase in the short term procedural safety but may limit the chance of in training nephrologists to become confident with the technique. METHODS: We evaluated renal biopsies performed from May 2002 to October 2016 in our Hospital, a mid-sized facility to determine whether the occurrence of complications would be comparable to those reported in literature and whether the increase in the number of biopsy performing physicians including nephrology fellows which took place since January 2012, after our Nephrology Unit became academic, would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies. Three hundred thirty seven biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24 h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the biopsy. RESULTS: Complications occurred in 18.7% of patients, of these only 1,2% were major complications. Complications were more common in female (28%) compared to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis, kidney function and complication rates; hypertension was not associated to a higher risk in complications. The increase of biopsy performing personnel was not associated to an increase in complication rates (18,7% both pre and post 2012) or with an increase of major complications (1.2% vs 1,2%). CONCLUSIONS: Kidney biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are guaranteed even if the procedure is performed by a larger number of less experienced nephrologists as long as under tutor supervision, thus kidney biopsy should become an integral part of a nephrology fellow training allowing more widespread diffusion of this technique.