Dietary protein restriction is an important treatment for chronic kidney disease. Herein, we tested the effect of low-protein or low-protein plus ketoacids (KA) diet in a remnant kidney model. Rats with a remnant kidney were randomized to receive normal protein diet (22%), low-protein (6%) diet (LPD), or low-protein (5%) plus KA (1%) diet for 6 months. Protein restriction prevented proteinuria, decreased blood urea nitrogen levels, and renal lesions; however, the LPD retarded growth and decreased serum albumin levels. Supplementation with KA corrected these abnormalities and provided superior renal protection compared with protein restriction alone. The levels of Kruppel-like factor-15 (KLF15), a transcription factor shown to reduce cardiac fibrosis, were decreased in remnant kidneys. Protein restriction, which increased KLF15 levels in the normal kidney, partially recovered the levels of KLF15 in remnant kidney. The expression of KLF15 in mesangial cells was repressed by oxidative stress, transforming growth factor-β, and tumor necrosis factor (TNF)-α. The suppressive effect of TNF-α on KLF15 expression was mediated by TNF receptor-1 and nuclear factor-κB. Overexpression of KLF15 in mesangial and HEK293 cells significantly decreased fibronectin and type IV collagen mRNA levels. Furthermore, KLF15 knockout mice developed glomerulosclerosis following uninephrectomy. Thus, KLF15 may be an antifibrotic factor in the kidney, and its decreased expression may contribute to the progression of kidney disease.

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.

Introduction Patients on dialysis (HDP) 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 towards COVID-19 vaccination in HDP. Methods HDP were surveyed with an ad hoc questionnaire in four large dialysis facilities in Europe: Le Mans and Paris, in France, 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 healthcare system. Results 417 patients (average age 69, 60% men) agreed to answer the questionnaire. Hesitancy was associated with younger age (p 0.003), lower perception of disease severity (<0.001) and vaccine efficacy (p<0.001), lower trust in vaccination (p<0.001) and in the healthcare system and scientists (p<0.001) in the univariate analysis. In the multivariate models, concerns about side effects (p 0.004) and vaccine efficacy (<0.001) and living in France (p 0.04) remained associated with higher vaccine hesitancy, while having received an influenza vaccine (p 0.032) and trusting scientists (p 0.032) were associated with a more positive attitude towards vaccination. Conclusions HDP 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. HDP were quite skeptical about the healthcare system but generally trusted scientists.

Background: Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. Objectives: The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. Methods: We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 ± 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 ± 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 ± 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (D_CO), corrected for both Hb values (D_CO*) and alveolar volume (K_CO), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. Results: All patients in group A showed normal PFTs, D_CO* and K_CO values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced D_CO* (63 ± 8%), elevated K_CO values (120 ± 14%), a variable degree of hypoxia (P_O2 82 ± 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced D_CO* values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, D_CO* was negatively correlated with both serum ferritin (r = –0.58; p < 0.05) and age (r = –0.57; p < 0.05). Conclusions: The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.