Prehydrated Electrons Activated by Continuous Electron Transfer Stemmed from Peracetic Acid Homolysis Mediated by Diamond Surface Defects for Enhanced PFOA Destruction.

Research on the use of peracetic acid (PAA) activated by nonmetal solid catalysts for the removal of dissolved refractory organic compounds has gained attention recently due to its improved efficiency and suitability for advanced water treatment (AWT). Among these catalysts, nanocarbon (NC) stands out as an exceptional example. In the NC-based peroxide AWT studies, the focus on the mechanism involving multimedia coordination on the NC surface (reactive species (RS) path, electron reduction non-RS pathway, and singlet oxygen non-RS path) has been confined to the one-step electron reaction, leaving the mechanisms of multichannel or continuous electron transfer paths unexplored. Moreover, there are very few studies that have identified the nonfree radical pathway initiated by electron transfer within PAA AWT. In this study, the complete decomposition (kobs = 0.1995) and significant defluorination of perfluorooctanoic acid (PFOA, deF% = 72%) through PAA/NC has been confirmed. Through the use of multiple electrochemical monitors and the exploration of current diffusion effects, the process of electron reception and conduction stimulated by PAA activation was examined, leading to the discovery of the dynamic process from the PAA molecule → NC solid surface → target object. The vital role of prehydrated electrons (epre-) before the entry of resolvable electrons into the aqueous phase was also detailed. To the best of our knowledge, this is the first instance of identifying the nonradical mechanism of continuous electron transfer in PAA-based AWT, which deviates from the previously identified mechanisms of singlet oxygen, single-electron, or double-electron single-path transfer. The pathway, along with the strong reducibility of epre- initiated by this pathway, has been proven to be essential in reducing the need for catalysts and chemicals in AWT.

Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor.

Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients.

Successful definitive radiation treatment of refractory canine oral papillomatosis.

This case report describes a three-year-old male intact border collie diagnosed with canine papillomavirus type 1 (CPV-1+) oral papillomas resistant to standard-of-care. With time, he developed lesions consistent with squamous cell carcinoma. Malignant tumors were incompletely excised and treated with definitive external beam radiation therapy (45 Gy, 3 Gy × 15 daily). The remaining oral cavity received 27 Gy (1.8 Gy x 15 daily) to treat the disseminated oral papillomatosis. A temporary treatment delay of 2 weeks was instituted due to grade 3 mucositis. The patient remained in complete remission after 10 months from radiotherapy. No tumor recurrences were noted by the owners after >1 year from treatment.

What about the Use of Ice Cream as a Supplementary Diet in Chronic Kidney Disease? A Case-Control Study.

Maintaining a healthy lifestyle can extend life expectancy and improve a person's health status. In addition to physical activity and bad habits related to smoking and alcohol, diet is also a determining factor. Following a healthy diet pattern over time and supporting a healthy body weight contributes to reducing the risk of developing more severe complications associated with very common diseases such as chronic kidney disease (CKD), diabetes, or cardiovascular diseases. The 2015-2020 Dietary Guidelines for Americans promote the adoption of fat-free or low-fat diets and discourage the consumption of foods with added sugar and solid fats, such as ice creams and other frozen desserts. On the other hand, ice cream, from a nutritional and healthy point of view, can be considered a possible food choice, due to its greater palatability and high nutritional content, but its consumption must be scheduled in a balanced diet. In this retrospective study, 36 patients with chronic renal failure were enrolled. Two different diets were proposed (A and B). In Diet B, lemon sorbet was added twice a week as an alternative food to replace fruit or snacks making the diet more varied and palatable. Nutritional status and biohumoral, immunological, and blood parameters were evaluated after 6 months. A statistical analysis shows a significant inter-group difference in creatinine and azotemia between T0 and T1. Intra-group significant differences were found in lymphocytes (p = 0.005) and azotemia (p < 0.001) in Diet A, and in azotemia (p < 0.001) and transferrin (p < 0.001) in Diet B. The results indicated that ice cream represented a good alternative food in both groups of patients regarding nutritional values and patient satisfaction. Furthermore, the treatment with ice cream allowed for better control of azotemia, maintaining stable levels even in patients with advanced CKD. This study concludes that ice cream could exert beneficial effects in addition to CKD patients' dietary regimens.

Financial Toxicity in Renal Patients (FINTORE) Study: A Cross-Sectional Italian Study on Financial Burden in Kidney Disease-A Project Protocol.

Financial toxicity (FT) refers to the negative impact of health-care costs on clinical conditions. In general, social determinants of health, especially poverty, socioenvironmental stressors, and psychological factors, are increasingly recognized as important determinants of non-communicable diseases, such as chronic kidney disease (CKD), and their consequences. We aim to investigate the prevalence of FT in patients at different stages of CKD treated in our universal health-care system and from pediatric nephrology, hemodialysis, peritoneal dialysis and renal transplantation clinics. FT will be assessed with the Patient-Reported Outcome for Fighting Financial Toxicity (PROFFIT) score, which was first developed by Italian oncologists. Our local ethics committee has approved the study. Our population sample will answer the sixteen questions of the PROFFIT questionnaire, seven of which are related to the outcome and nine the determinants of FT. Data will be analyzed in the pediatric and adult populations and by group stratification. We are confident that this study will raise awareness among health-care professionals of the high risk of adverse health outcomes in patients who have both kidney disease and high levels of FT. Strategies to reduce FT should be implemented to improve the standard of care for people with kidney disease and lead to truly patient-centered care.

Investigational new drugs for the treatment of chronic renal failure: an overview of the literature.

INTRODUCTION: Chronic kidney disease (CKD) is widespread throughout the world, with a high social and health impact. It is considered a 'silent killer' for its sudden onset without symptoms in the early stages of the disease. The main goal of nephrologists is to slow the progression of kidney disease and treat the associated symptoms with a range of new medications. AREAS COVERED: The aim of this systematic review is to analyze the new investigational drugs for the treatment of chronic renal failure. Data were obtained from the available scientific literature and from the ClinicalTrials.gov website. EXPERT OPINION: Among the drugs currently being researched, SGLT2 inhibitors appear to be the most promising drugs for the treatment of CKD, has they have slower progression of CKD and protection of cardiorenal function. An important role in the future of CKD treatment is played by autologous cell-therapy, which appears to be a new frontier in the treatment of CKD. Other therapeutic strategies are currently being investigated and have been shown to slow the progression of CKD. However, further studies are needed to determine whether these approaches may offer benefits in slowing the progression of CKD in the near future.

A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence.

Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.

Pregnancy in Glomerular Disease: From Risk Identification to Counseling and Management.

Background: Pregnancy involves complex hemodynamic and immune adaptations to support the developing fetus. The kidney assumes a pivotal role in orchestrating these mechanisms. However, renal disease poses a potential risk for adverse maternal-fetal outcomes. While kidney function, hypertension, and proteinuria are recognized as key influencers of risk, the mere presence of glomerular disease, independent of these factors, may wield significant impact. Methods: A brief review of the existing literature was conducted to synthesize current knowledge regarding the interplay between glomerulonephritis and pregnancy. Results: The review underscores the centrality of the kidney in the context of pregnancy and highlights the role of glomerular disease, particularly when active. It emphasizes multifaceted risk modulators, including kidney function, hypertension, and proteinuria. Conclusion: Understanding the dynamics between pregnancy and glomerulonephritis is crucial for optimizing maternal and fetal outcomes. Preconception counseling and collaborative nephro-gynecological management emerge as pivotal components in addressing the unique challenges posed by this medical interplay.

Comparison between dexmedetomidine and a combination of medetomidine-vatinoxan on muscle tissue saturation in privately-owned adult dogs undergoing intradermal testing.

This double-blinded randomized cross-over study compared the muscle tissue oxygen saturation (StO2) measured at the sartorius muscle after intramuscular (IM) injection of dexmedetomidine hydrochloride (HCl) and co-administration of vatinoxan HCl, a peripheral α2-adrenoceptor antagonist, and medetomidine HCl in healthy privately-owned dogs undergoing intradermal testing (IDAT). After written owner consent, dogs received IM injections of either dexmedetomidine (0.5 mg/m2, DEX) or medetomidine (1 mg/m2) and vatinoxan (20 mg/m2) (MVX). Once sedated, intradermal injections were given on the lateral thorax of each dog, and the study was repeated with the alternative sedation on the opposite side one week later. At the end of the study, sedation was reversed with atipamezole (5 mg/m2). Depth of sedation, cardiopulmonary parameters, StO2, and rectal temperature were recorded and compared using mixed effect linear models (α ≤ 0.05). MVX achieved adequate sedation faster [median (interquartile range), 10 (8, 10) minutes] compared to DEX [18 (15, 22) minutes; hazard ratio = 7.44, p = 0.013), with higher scores at 10- and 15-min post-injection. StO2 was significantly reduced for 30 min after injection (p < 0.001), independently of the treatment (p = 0.68). Cardiopulmonary variables favored MVX. However, higher heart rate did not correlate with improved StO2. There was no difference in either subjective or objective assessment of the wheal size between sedations (p > 0.05). Both sedation protocols, MVX and DEX, were deemed suitable for IDAT in dogs, with mild reductions in StO2 measured at the sartorius muscle that were not significantly different between treatments.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Update on the role of cytokines and chemokines in canine atopic dermatitis.

BACKGROUND: Cytokines and chemokines play central roles in the pathogenesis of canine atopic dermatitis (cAD). Numerous studies have been published and provide new insights into their roles in cAD. OBJECTIVES: To summarise the research updates on the role of cytokines and chemokines in the pathogenesis of cAD since the last review by the International Committee on Allergic Diseases of Animals in 2015. MATERIAL AND METHODS: Online citation databases, abstracts and proceedings from international meetings on cytokines and chemokines relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Advances in technologies have allowed the simultaneous analysis of a broader range of cytokines and chemokines, which revealed an upregulation of a multipolar immunological axis (Th1, Th2, Th17 and Th22) in cAD. Most studies focused on specific cytokines, which were proposed as potential novel biomarkers and/or therapeutic targets for cAD, such as interleukin-31. Most other cytokines and chemokines had inconsistent results, perhaps as a consequence of their varied involvement in the pathogenesis of different endotypes of cAD. CONCLUSIONS AND CLINICAL RELEVANCE: Inconsistent results for many cytokines and chemokines illustrate the difficulty of studying the complex cytokine and chemokine networks in cAD, and highlight the need for more comprehensive and structured studies in the future.

Update on the role of genetic factors, environmental factors and allergens in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation. OBJECTIVE: This review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015. MATERIALS AND METHODS: Online citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Despite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome-wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat-based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae-induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1. CONCLUSIONS AND CLINICAL RELEVANCE: Canine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well-designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.

Update on the skin barrier, cutaneous microbiome and host defence peptides in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (AD) is a complex inflammatory skin disease associated with cutaneous microbiome, immunological and skin barrier alterations. This review summarises the current evidence on skin barrier defects and on cutaneous microbiome dysfunction in canine AD. OBJECTIVE: To this aim, online citation databases, abstracts and proceedings from international meetings on skin barrier and cutaneous microbiome published between 2015 and 2023 were reviewed. RESULTS: Since the last update on the pathogenesis of canine AD, published by the International Committee on Allergic Diseases of Animals in 2015, 49 articles have been published on skin barrier function, cutaneous/aural innate immunity and the cutaneous/aural microbiome in atopic dogs. Skin barrier dysfunction and cutaneous microbial dysbiosis are essential players in the pathogenesis of canine AD. It is still unclear if such alterations are primary or secondary to cutaneous inflammation, although some evidence supports their primary involvement in the pathogenesis of canine AD. CONCLUSION AND CLINICAL RELEVANCE: Although many studies have been published since 2015, the understanding of the cutaneous host-microbe interaction is still unclear, as is the role that cutaneous dysbiosis plays in the development and/or worsening of canine AD. More studies are needed aiming to design new therapeutic approaches to restore the skin barrier, to increase and optimise the cutaneous natural defences, and to rebalance the cutaneous microbiome.

Review and Practical Excursus of the Propensity Score: Low Protein Diet Compared to Mediterranean Diet in Patients With Chronic Kidney Disease.

Although Randomized clinical trials (RCT) represent the gold standard to compare two or more treatments, the impact of observational studies cannot be ignored. Obviously, these latter are performed on unbalanced sample, and differences among the compared groups could be detected. These differences could have an impact on the estimated association between our allocation and our outcome. To avoid it, some methods should be applied in the analysis of observational cohort. Propensity score (PS) can be considered as a value which sums up and balances the known variables. It aims to adjust or balance the probability of receiving a specific allocation group, and could be used to match, stratify, weight, and perform a covariate adjustment. PS is calculated with a logistic regression, using allocation groups as the outcome. Thanks to PS, we compute the probability of being allocated to one group and we can match patients obtaining two balanced groups. It avoids computing analysis in unbalanced groups. We compared low protein diet (LPD) and the Mediterranean diet in CKD patients and analysed them using the PS methods. Nutritional therapy is fundamental for the prevention, progression and treatment of Chronic Kidney Disease (CKD) and its complications. An individualized, stepwise approach is essential to guarantee high adherence to nutritional patterns and to reach therapeutic goals. The best dietary regimen is still a matter of discussion. In our example, unbalanced analysis showed a significant renal function preservation in LPD, but this correlation was denied after the PS analysis. In conclusion, although unmatched analysis showed differences between the two diets, after propensity analysis no differences were detected. If RCT cannot be performed, balancing the PS score allows to balance the sample and avoids biased results.

How to Choose the Right Treatment for Membranous Nephropathy.

Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation.

Canine Models of Inflammatory Skin Diseases and Their Application in Pharmacological Research.

The purpose of this article is to provide an overview of existing pharmacological models of canine dermatitis. Canine models of dermatitis have contributed significantly to our current understanding of the pathology of dermatitis and to the development of corresponding pharmacological interventions. Specifically, canine atopic dermatitis (AD) is reviewed here, as it is one of the most common inflammatory skin diseases in dogs. Canine AD also shares clinicopathological features with human AD, making the dog a natural and optimal model for human disease. Thus, pharmacological models of canine AD may be uniquely applicable to human pharmacological research. In this article, particular attention is dedicated to relevant in vivo, in vitro, and ex vivo models of canine AD, skin barrier defect models, pruritus models, and skin immunology models. Additionally, models of superficial pyoderma and food allergy are also discussed. With understanding of findings from canine models, researchers can select the most salient features for future pharmacological drug development. © 2023 Wiley Periodicals LLC.

Personalized Medicine in Kidney Disease.

The Special Issue "Personalized Medicine in Kidney Disease" is focused on the importance of customized medicine in nephrology as it represents one of the main characteristics of successful therapeutic results [...].