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Background: Central Venous Catheter (CVC)-related infections cannot always be solved by replacement, due to some vascular anomalies or an emergency status. This comprehensive, evidence-based review aimed to define the efficacy of antibacterial lock therapy (ALT) compared to the standard of care (SoC) in CVC-related infections. Methods: We performed a systematic search in PubMed, Embase, and Google Scholar, looking for randomized controlled trials (RCTs) and cohort or case-control observational studies. The eligible studies considered the subjects with a diagnosis of CVC-related infections treated with antibacterial lock therapy (ALT) compared to the standard of care (SoC). Results: Among 609 records at the end of the selection process, five articles, referring to observational studies, were included in this systematic review. In pooled analyses, including a total of 276 individuals, microbiological healing (OR 3.78; 95% CI; 2.03–7.03) showed significant differences between ALT and the SoC, with a follow-up varying from 2 weeks to 3 months. Conclusions: Our results suggested that ALT could improve the preservation of CVCs and could be considered when their replacement is not possible as a result of vascular problems. However, only observational studies were included and RCTs are needed to confirm these findings and to increase the level of evidence.

Abstract Advances in sensor, computing, and communication technologies are enabling big data analytics by providing time series data. However, conventional models struggle to identify sequence features and forecast accuracy. This paper investigates time series features and shows that some machine learning algorithms can outperform deep learning models. In particular, the problem analyzed concerned predicting the number of vehicles passing through an Italian tollbooth in 2021. The dataset, composed of 8766 rows and 6 columns relating to additional tollbooths, proved to have high stationarity and was treated through machine learning methods such as support vector machine, random forest, and eXtreme gradient boosting (XGBoost), as well as deep learning through recurrent neural networks with long short-term memory (RNN-LSTM) cells. From the comparison of these models, the prediction through the XGBoost algorithm outperforms competing algorithms, particularly in terms of MAE and MSE. The result highlights how a shallower algorithm than a neural network is, in this case, able to obtain a better adaptation to the time series instead of a much deeper model that tends to develop a smoother prediction.

Chronic kidney disease (CKD) in older individuals is a matter of growing concern in the field of public health across the globe. Indeed, prevalence of kidney function impairment increases with advancing age and is often exacerbated by age-induced modifications of kidney function, presence of chronic diseases such as diabetes, hypertension, and cardiovascular disorders, and increased burden related to frailty, cognitive impairment and sarcopenia. Accurate assessment of CKD in older individuals is crucial for timely intervention and management and relies heavily on biomarkers for disease diagnosis and monitoring. However, the interpretation of these biomarkers in older patients may be complex due to interplays between CKD, aging, chronic diseases and geriatric syndromes. Biomarkers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria can be significantly altered by systemic inflammation, metabolic changes, and medication use commonly seen in this population. To overcome the limitations of traditional biomarkers, several innovative proteins have been investigated as potential, in this review we aimed at consolidating the existing data concerning the geriatric aspects of CKD, describing the challenges and considerations in using traditional and innovative biomarkers to assess CKD in older patients, highlighting the need for integration of the clinical context to improve biomarkers’ accuracy.

Copper is an essential element in the diet of mammals, including humans. It plays an important role in the physiological regulation of various enzymes and is consequently involved in several biological processes such as angiogenesis, oxidative stress regulation, neuromodulation, and erythropoiesis. Copper is essential for facilitating the transfer of iron from cells to the bloodstream, which is necessary for proper absorption of dietary iron and the distribution of iron throughout the body. In particular, patients with end-stage renal failure who require renal replacement therapy are at increased risk for disorders of copper metabolism. Many studies on hemodialysis, peritoneal dialysis, and kidney transplant patients have focused on serum copper levels. Some reported mild deficiency, while others reported elevated levels or even toxicity. In some cases, it has been reported that alterations in copper metabolism lead to an increased risk of cardiovascular disease, malnutrition, anemia, or mielopathy. The aim of this review is to evaluate the role of copper in patients undergoing hemodialysis and its potential clinical implications.

BackgroundInternational and national registries consistently report substantial differences in kidney transplant (KT) activity despite demonstrable clinical and financial benefits. The study aims to estimate the financial resources gained by KT and produce a benchmark analysis that would inform adequate strategies for the growth of the service.MethodsWe analyzed the KT activity in our region between 2017 and 2019. The benchmark analysis was conducted with programs identified from national and international registries. The estimate of financial resources was obtained by applying the kidney transplant coefficient of value; subsequently, we compared the different activity levels and savings generated by the three KT programs.FindingsThe KT activity in the region progressively declined in the study years, producing a parallel reduction of the estimated savings. Such savings were substantially inferior when compared to those generated by benchmark programs (range €18–22 million less).InterpretationThe factors influencing the reduced KT activity in the study period with the related “foregone savings” are multiple, as well as interdependent. Organ donation, access to the transplant waiting list, and KT from living donors appear to be the most prominent determinants of the observed different levels of activities. International experience suggests that a comprehensive strategy in the form of a “task force” may successfully address the critical areas of the service reversing the observed trend. The financial impact of a progressively reduced KT activity may be as critical as its clinical implications, jeopardizing the actual sustainability of services for patients with end-stage kidney disease.

Geothermal resources represent precious energy sources to ensure sustainable power generation. As proposed in the majority of the future sustainable energy scenarios, geothermal energy exploitation is going to play a significant role in the energy mix to meet carbon neutrality target. Upon the different technologies involved, geothermal wells constitute the core and turning point for proper fluid/heat mining. Indeed, the number of suitable candidates for geothermal applications could be significantly enhanced by overcoming a series of wells related technological issues. Therefore, the object of this work is to provide a general overview of the principal challenges that characterized well design and construction in geothermal applications which are mainly related to the type of geological system and its relative temperature level. As a matter of fact, reservoir temperature guides most of the choices referring to geothermal systems not only in the selection of the final energy application purpose (direct use, power generation, combined heat and power) but also in well design definition. Based on temperature range, geothermal fields are usually grouped in enthalpy classes (low, medium and high) referring to fields characterized by similar energy potential. From a well design and construction perspective, the low and medium enthalpy classes, in the range of temperature lower than 150 °C, do not present specific criticalities. On the contrary, high enthalpy scenarios, for temperatures higher than 170 °C, present many challenges for most of the current drilling and completion technologies. Even though some field applications exist in high/ultra-high enthalpy scenarios, they still present an elevated risk of failure. Therefore, dedicated studies shall be conducted for all the elements involved in the well construction process such as: drilling fluids, cement slurry, metallurgy, drilling and completion equipment to properly account for their specific technical limitations. In this framework, a clear picture of the actual technical gaps constitutes the starting point for current and next research activities. In the close future, the growing interest in geothermal applications will surely boost the born and development of dedicated tools to unlock the enormous potential of geothermal energy.

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 (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.

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.

BackgroundIn this study, the Keynesian principle “savings may be used as investments in resources” is applied to Kidney Transplantation (KT), contextualizing the whole Organs Donation and Transplantation (ODT) service as a unique healthcare entity. Our aim was to define the financial resources that may be acquired in the form of savings from the KT activity.MethodsWe analyzed registry and funding data for ODT in our region, between 2015 and 2019. Our hypotheses aimed to evaluate whether the savings would offset the Organ Donation (OD) costs, define the scope for growth, and estimate what savings could be generated by higher KT activity. To facilitate the evaluation of the resources produced by KT, we defined a coefficient generated from the combination of clinical outcomes, activity, and costs.ResultsThe ODT activity reached a peak in 2017, declining through 2018–2019. The savings matured in 2019 from the KT activity exceeded €15 million while the OD costs were less than €9 million. The regional KT activity was superior to the national average but inferior to international benchmarks. The estimated higher KT activity would produce savings between €16 and 20 million.ConclusionThe financial resources produced by KT contribute to defining a comprehensive perspective of ODT finance. The optimization of the funding process may lead to the financial self-sufficiency of the ODT service. The reproducible coefficient allows a reliable estimate of savings, subsequently enabling adequate investments and budgeting. Applying such a perspective jointly with reliable estimates would establish the basis for an in-hospital fee-for-value funding methodology for ODT.

Introduction: It is not fully elucidated whether preeclampsia (PE) is a marker or a cause of chronic kidney disease (CKD). To test the hypothesis of a biphasic relationship between PE and CKD, we assessed PE prevalence in women who underwent a kidney biopsy. Methods: This retrospective, observational study recruited patients who underwent a kidney biopsy after delivery in 2014 to 2019 in 3 Italian Centers (Cagliari, Bari, Messina); low-risk pregnancies observed in Cagliari served as controls. A history of PE was assessed on the clinical charts and by phone interview. Results: In the biopsy cohort (379 pregnancies, 205 patients; 38 PE in 32 patients), kidney biopsy shows clustering in the first 5 years after PE (11 of 32). Pre-existing CKD was detected in 8 of 11 of these cases. Focal-segmental glomerulosclerosis (FSGS) and complex lesions were found in 12 of 32 biopsies. The odds ratio (OR) of having had a PE episode, compared with 561 low-risk pregnancies, was 10.071 (95% CI: 4.859–20.875; P < 0.001); multiparity maintained a protective effect (OR: 0.208). The delivery-to-biopsy time was significantly shorter in women with PE, both considering the first or the last PE versus the first or last delivery in patients with or without PE episodes. The characteristics of PE did not differ as compared with low-risk controls. Conclusion: Within the limitation of the retrospective design, our study, quantifying the association between needing a kidney biopsy and history of PE, suggests a biphasic pattern, with a peak in the first 5 years after delivery (probably due to pre-existing diseases) and a later increase, suggesting that PE may have later played as one hit in a multiple-hit pathogenesis.

The ongoing glomerular damage of infections is not limited to the most widely known form of post-streptococcal glomerulonephritis, which is today less common in the Western world; other forms of glomerulonephritis are associated with several bacterial, viral and parasitic pathogens. The mechanisms responsible range from the direct damage of glomerular cells to the formation and deposition of immunocomplexes to molecular mimicry to the secretion of superantigens. Similarly, in the course of glomerular disease, infections are more frequent than in the general population due to the loss of immunoglobulins in urine and the immunosuppressive agents used to treat the autoimmune disease that decrease the activity of the immune system. Recognizing this two-way link, understanding its pathogenetic mechanism, and identifying the most appropriate therapeutic choice are essential for the personalized management of patients. In this continuously developing field, this short review summarizes the current state of the art as support for physicians, who are increasingly involved in managing patients with glomerular disease and infections.

There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = −0.57, p < 0.001 for major fractures and r = −0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1–L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (β = −15.21, SE = 5.91, p = 0.02) and TBS (β = −54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.

Hyperphosphatemia is a common complication in advanced chronic kidney disease and contributes to cardiovascular morbidity and mortality. The present narrative review focuses on the management of phosphatemia in uremic patients receiving peritoneal dialysis. These patients frequently develop hyperphosphatemia since phosphate anion behaves as a middle-size molecule despite its low molecular weight. Accordingly, patient transporter characteristics and peritoneal dialysis modalities and prescriptions remarkably influence serum phosphate control. Given that phosphate peritoneal removal is often insufficient, especially in lower transporters, patients are often prescribed phosphate binders whose use in peritoneal dialysis is primarily based on clinical trials conducted in hemodialysis because very few studies have been performed solely in peritoneal dialysis populations. A crucial role in phosphate control among peritoneal dialysis patients is played by diet, which must help in reducing phosphorous intake while preventing malnutrition. Moreover, residual renal function, which is preserved in most peritoneal dialysis patients, significantly contributes to maintaining phosphate balance. The inadequate serum phosphate control observed in many patients on peritoneal dialysis highlights the need for large and well-designed clinical trials including exclusively peritoneal dialysis patients to evaluate the effects of a multiple therapeutic approach on serum phosphate control and on hard clinical outcomes in this high-risk population.

Pythium insidiosum, an aquatic oomycete with pathogenic potential in mammals, causes gastrointestinal and cutaneous disease in dogs. Mefenoxam, an agricultural anti-oomycotic compound, has a demonstrated the ability to inhibit P. insidiosum growth in vitro and has been associated with efficacy in treating gastrointestinal pythiosis in several case reports. Electronic medical records of dogs seen at University of Florida Small Animal Hospital and treated with mefenoxam between 2013 and 2020 were searched. Dogs were included in this study upon previous definitive diagnosis with either organism identification using culture, PCR, or antibody ELISA, or a combination of these tests with or without supportive histopathological analysis. Since 2013, mefenoxam had been administered to 25 dogs with cutaneous pythiosis and 16 dogs with gastrointestinal pythiosis. In both gastrointestinal and cutaneous pythiosis groups, the administration of mefenoxam was associated with a survivability rate of approximately 51%. There was a statistically significant difference in the time to death between cutaneous (245 days (52–530)) and gastrointestinal (90 days (21–203)) groups; dogs infected with cutaneous pythiosis survived significantly longer after being diagnosed with the disease (p = 0.035). The dogs in this study experienced increased survival rates and time to death, in the absence of side effects due to mefenoxam, compared with previously published literature. The results of this retrospective study, with some limitations, are promising and should prompt further investigation into the use of mefenoxam in the treatment of both gastrointestinal and cutaneous pythiosis.

Modelling conversion processes in sewers can help minimize odour and pipe corrosion issues, but model uncertainties and errors must be understood. In this study, the Wastewater Aerobic/Anaerobic Transformation in Sewers (WATS) model is implemented in two different frameworks; 1-D (CSTR-in-series) and computational fluid dynamics (CFD) to study the uncertainties due to model parameters and its mathematical form. The 1-D model is used to conduct uncertainty/sensitivity analysis using Monte Carlo simulations. Time-averaged outputs were represented using a general linearized model to quantify the importance of specific parameters. The sulfide formation rate per unit area of the biofilm is the most influential parameter. Parameters controlling anaerobic hydrolysis and fermentation are also significant. Uncertainty due to model structure is studied using CFD to explore the influences of non-homogeneous surface reactions and solids settling. These showed that the 1-D model provides a reasonable characterisation of the process for simple flows in pressure mains. HIGHLIGHTS Monte Carlo simulations reveal the most important parameters in sewer model.; Sulfide formation, anaerobic hydrolysis, fermentation parameters are most significant.; Fluid dynamics simulations show biofilm reaction homogenization is appropriate.; Solids settling can be neglected in pressure mains with continuous flow.;

The number of organic pollutants detected in water and wastewater is continuously increasing thus causing additional concerns about their impact on public and environmental health. Therefore, catalytic processes have gained interest as they can produce radicals able to degrade recalcitrant micropollutants. Specifically, catalytic ozonation has received considerable attention due to its ability to achieve advanced treatment performances at reduced ozone doses. This study surveys and summarizes the application of catalytic ozonation in water and wastewater treatment, paying attention to both homogeneous and heterogeneous catalysts. This review integrates bibliometric analysis using VOS viewer with systematic paper reviews, to obtain detailed summary tables where process and operational parameters relevant to catalytic ozonation are reported. New insights emerging from heterogeneous and homogenous catalytic ozonation applied to water and wastewater treatment for the removal of organic pollutants in water have emerged and are discussed in this paper. Finally, the activities of a variety of heterogeneous catalysts have been assessed using their chemical–physical parameters such as point of zero charge (PZC), pKa, and pH, which can determine the effect of the catalysts (positive or negative) on catalytic ozonation processes.

Introduction. Since the pandemic of Coronavirus Disease 2019 (COVID-19) started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-Stage Renal Disease (ESRD) patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune system. Vaccination on dialysis patients (DP) still remains challenging, because of the variable response and low seroconversion rate compared with healthy controls (HC). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of dose and administration time. Methods. Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HC were evaluated by absolute quantification of IgG levels in the blood. Results. DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HC. While healthy populations reached complete seroconversion within 10 days from the administration of second dose, only 76% of DP were seropositive. After booster dose, DP strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels. Discussion/Conclusion. These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since few data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after booster vaccine dose.

Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects.

Copper is a fundamental element for the homeostasis of the body. It is the third most abundant essential transition metal in humans. Changes in the concentration of copper in the blood are responsible for numerous diseases affecting various organs, including the heart, brain, kidneys, and liver. Even small copper deficiencies can lead to the development and progression of several pathologies. On the other hand, excessive exposure to copper can cause toxicity in many human organs, leading to various systemic alterations. In the kidney, increased copper concentration in the blood can cause deposition of this element in the kidneys, leading to nephrotoxicity. One of the most interesting aspects of copper balance is its influence on diabetes and the progression of its complications, such as Diabetic Kidney Disease (DKD). Several studies have shown a close relationship between copper serum levels and altered glycemic control. An imbalance of copper can lead to the progression of diabetes-related complications and impaired antioxidant homeostasis. A high Zinc/Copper (Zn/Cu) ratio is associated with improved renal function and reduced risk of poor glycemic control in patients with type two diabetes mellitus (T2DM). Furthermore, the progression of DKD appears to be related to the extent of urinary copper excretion, while regulation of adequate serum copper concentration appears to prevent and treat DKD. The aim of this review is to evaluate the possible role of copper in DKD patients.

Coagulase positive Staphylococci (CoPS) are the leading cause of canine cutaneous and otic infections. Virulence factors associated with Staphylococci include the expression of mec and panton-valentine leukocidin (pvl) genes. Methicillin-resistance (MR) is commonly associated with mecA gene expression, although a recently identified variant, mecC, has been reported. This study aims to evaluate the prevalence of mecA, mecC and pvl genes in 232 clinical isolates of CoPS collected from dogs with pyoderma. A multiplex PCR, and Kirby-Bauer disk diffusion susceptibility test for cefoxitin was performed for all isolates. PBP2a agglutination test was performed on 127 isolates. Standard MRSA isolates were used as positive controls. The mecA gene was identified in 149/232 isolates (64.2%): 116 S. pseudintermedius, 30 S. coagulans and three S. aureus. The pvl gene was present in only 1 isolate of S. pseudintermedius (0.4%), whereas no isolates carried the mecC gene. 34 isolates were resistant to cefoxitin (14.6%) and they were all mecA positive. The results of this study show an MR prevalence of 64.2% confirming concerns about antibiotic resistance in veterinary medicine. In conclusion, this is the first study analyzing the prevalence of mecC and pvl in comparison to mecA, in a large cohort of CoPS clinical isolates from dogs with pyoderma. A multimodal surveillance on the prevalence of mecC and pvl in veterinary medicine is essential to appropriate antimicrobial management.

Background: Henoch-Schönlein purpura (HSP) is a common systemic vasculitis in children, involving the skin, musculoskeletal system, gastrointestinal tract and kidneys. Some studies in children have shown possible risk factors linked with the development and severity of HSP Nephritis (HSPN). The aim of this study was to research predicting factors for the development of HSPN. Methods: We retrospectively evaluated 132 pediatric patients with HSP, according to EULAR/PRINTO/PRESS criteria. All patients were screened for HSPN by urinalysis. Finally, we compared demographic, clinical and laboratory data in HSP patients with and without nephritis. Results: The median age at HSP diagnosis [6.2 (2.6–17.5) vs. 5.5 (0.8–15.4) years, p = 0.03] and the incidence of abdominal pain (48 vs. 27%, p = 0.01) were significantly higher in HSPN patients. No differences were evidenced regarding gender, allergic diseases, skin recurrences, gastrointestinal involvement, musculoskeletal involvement, scrotal involvement, and laboratory data (white blood cell count, neutrophil count, lymphocyte count, platelet count, C-reactive protein, erythrocyte sedimentation rate, and blood concentration of IgA). Conclusions: The age at diagnosis and abdominal pain were independent risk factors for renal involvement in HSP patients. However, due to the retrospective nature of this study, further long-term and prospective studies will be necessary.

Thanks to the development of increasingly sophisticated machine-learning techniques, it is possible to improve predictions of a particular phenomenon. In this paper, after analyzing data relating to the mobility habits of University of Foggia (UniFG) community members, we apply logistic regression and cross validation to determine the information that is missing in the dataset (so-called imputation process). Our goal is to make it possible to obtain the missing information that can be useful for calculating sustainability indicators and that allow the UniFG Rectorate to improve its sustainable mobility policies by encouraging methods that are as appropriate as possible to the users’ needs.

Abstract Background Evidences show that around 20% of biosimilar or originator erythropoiesis-stimulating agents (ESAs) users are hyporesponsive. Controversial post-marketing data exist on the predictors of ESA hyporesponsiveness. The aim of this study was to identify predictors of ESA hyporesponsiveness in patients with chronic kidney disease (CKD) or cancer in clinical practice. Methods During the years 2009–2015, a multi-center, population-based, cohort study was conducted using claims databases of Treviso and Caserta Local Health Units (LHUs). All incident ESA users were characterized at baseline and the differences between the baseline hemoglobin (Hb) value, that is the Hb registered within 30 days prior to the first ESA dispensing (index date, ID) and each outcome Hb value (registered between 30 and 180 days after ID) were calculated and defined as delta Hb (ΔHb). Incident ESA users were defined as hyporesponsive if, during follow-up, they registered at least one ΔHb

Patients with stages 4 and 5 chronic kidney disease (CKD), and particularly chronic dialysis patients, commonly are found to have substantially reduced daily physical activity in comparison to age- and sex-matched normal adults. This reduction in physical activity is associated with a major decrease in physical exercise capacity and physical performance. The CKD patients are often physically deconditioned, and protein energy wasting (PEW) and frailty are commonly present. These disorders are of major concern because physical dysfunction, muscle atrophy, and reduced muscle strength are associated with poor quality of life and increased morbidity and mortality in CKD and chronic dialysis patients. Many randomized controlled clinical trials indicate that when CKD and chronic dialysis are provided nutritional supplements or undergo exercise training their skeletal muscle mass and exercise capacity often increase. It is not known whether the rise in skeletal muscle mass and exercise capacity associated with nutritional support or exercise training will reduce morbidity or mortality rates. A limitation of these clinical trials is that the sample sizes of the different treatment groups were small. The aim of this review is to discuss the effects of nutrition and exercise on body composition, exercise capacity, and physical functioning in advanced CKD patients.

The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. NETs are composed of either DNA or nucleosome proteins and hundreds of cytoplasm proteins, a part of which undergo post-translational modification during the steps leading to NETs. There is a thin balance between the production and the removal of circulating NETs from blood where digestion of DNA by circulating DNases 1 and IL3 has a critical role. A delay in NET removal may have consequences for autoimmunity. Recent studies have shown that circulating NET levels are increased in systemic lupus erythematosus (SLE) for a functional block of NET removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations. In SLE, the persistence in circulation of NETs signifies elevated concentrations of either free DNA/nucleosome components and oxidized proteins that, in some cases, are recognized as non-self and presented to B-cells by Toll-like receptor 9 (TLR9). In this way, it is activated as an immunologic response, leading to the formation of IgG2 auto-antibody. Monitoring serum NET levels represents a potential new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NET formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE.Clinical Trial Registration Number: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Chronic kidney disease (CKD) affects 3% of pregnancies, impacting on maternal and fetal outcomes, and at the same time, a recurrent question in nephrology regards gestation impact on kidney function. Observational studies stated that CKD stage, pre-existent hypertension, and proteinuria are the main predictors of possible complications, such as maternal CKD progression, maternal or fetal death, prematurity, small for gestational age (SGA) newborn, or admission to the neonatal intensive care unit. In this regard, given the prominence of proteinuria among other risk factors, we focused on primary nephrotic syndrome in pregnancy, which accounts for 0.028% of cases, and its impact on materno-fetal outcomes and kidney survival. Data extracted from literature are scattered because of the small cohorts investigated in each trial. However, they showed different outcomes for each glomerular disease, with membranous nephropathy (MN) having a better maternal and fetal prognosis than focal and segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), or minimal change disease (MCD). Nephrotic syndrome does not have to discourage women to undertake a pregnancy, but the correct management may include a specific evaluation of risk factors and follow-up for adverse materno-fetal events and/or maternal kidney disease progression.

Diabetic Kidney Disease (DKD) represents the most common cause of Chronic Kidney Disease (CKD) in developed countries. Approximately 30% to 40% of diabetes mellitus (DM) subjects develop DKD, and its presence significantly increases the risk for morbidity and mortality. In this context, Zinc seems to have a potential role in kidney and body homeostasis in diabetic individuals as well as in patients at a high risk of developing this condition. This essential element has functions that may counteract diabetes-related risk factors and complications, which include stabilization of insulin hexamers and pancreatic insulin storage and improved glycemic control. In our review, we analyzed the current knowledge on the role of zinc in the management of renal impairment in course of DM. Several studies underline the critical role of zinc in reducing oxidative stress levels, which is considered the common denominator of the mechanisms responsible for the progression of kidney disease. Reaching and maintaining a proper serum zinc level could represent a valuable target to reduce symptoms related to DM complications and contrast the progression of kidney impairment in patients with the high risk of developing end-stage renal disease. In conclusion, analyzing the beneficial role of zinc in this review would advance our knowledge on the possible strategies of DM and DKD treatment.

A pathogenic Escherichia coli (E.coli) O157:H7 and O26:H11 dose-response model was set up for a quantitative microbial risk assessment (QMRA) of the waterborne diseases associated with managed aquifer recharge (MAR) practices in semiarid regions. The MAR facility at Forcatella (Southern Italy) was selected for the QMRA application. The target counts of pathogens incidentally exposed to hosts by eating contaminated raw crops or while bathing at beaches of the coastal area were determined by applying the Monte Carlo Markov Chain (MCMC) Bayesian method to the water sampling results. The MCMC provided the most probable pathogen count reaching the target and allowed for the minimization of the number of water samplings, and hence, reducing the associated costs. The sampling stations along the coast were positioned based on the results of a groundwater flow and pathogen transport model, which highlighted the preferential flow pathways of the transported E. coli in the fractured coastal aquifer. QMRA indicated tolerable (

Abstract Background A relationship between IgA nephropathy (IgAN) and celiac disease (CD) has been reported. We show the pathogenetic link for the first time. Case presentation A 39-year-old man with cystic fibrosis (CF) and CF-related diabetes started to present gross hematuria, back pain and headache. At admission, laboratory analysis showed increase in serum creatinine of 1.5 mg/dl, together with hematuria and mild proteinuria (1 g/24 h). He underwent a renal biopsy to investigate the cause of hematuria and renal failure. Biopsy was consistent with IgAN. In view of patient reported dyspepsia, an upper gastrointestinal endoscopy with duodenal biopsies was undertaken and was normal. We looked for mucosal deposits of tTG-2 in the duodenum and the renal mesangium. tTG-2 deposits were found both in the duodenum and in renal biopsies, where they topographically replicated mesangial IgA deposits. After one year on a continued gluten containing diet, the patient developed a Marsh 2 type duodenal pathology. Conclusions Our findings suggest a connection between CD and IgAN in terms of an immune-mediated gluten-induced pathogenesis even in the absence of villous atrophy and serum celiac autoantibodies.

Abstract Background C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN. Case presentation Our case involves a young woman with cystic fibrosis, who had persistent microscopic hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activation proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value

Ingestion of coffee (which is a mixture of over 1000 hydrosoluble substances) is known to protect from type-2 diabetes mellitus and its complications, and other chronic disorders associated with increased oxidative damage in blood and tissues. This protection is generally attributed to polyphenols and melanoidins. Very few studies were conducted on the amelioration of classic blood markers of oxidative stress induced after a few days of caffeine administration, but results vary.To assess whether caffeine per se could account for antioxidant properties of coffee in the short-term, we tested the ability of pure caffeine ingestion (5â¯mg/kg body weight/day in two daily doses for seven consecutive days) to improve plasma levels of six biochemical indices in healthy male volunteers (nâ¯=â¯15). These indices were total antioxidant capacity (TAC), glutathione (GSH), oxidized glutathione (GSSG), GSH to GSSG ratio, lipid hydroperoxides (LOOH) and malondialdehyde (MDA).We found that all indices changed significantly (Pâ¯

Cardiorenal syndrome (CRS) is a multi-organ disease characterized by the complex interaction between heart and kidney during acute or chronic injury. The pathogenesis of CRS involves metabolic, hemodynamic, neurohormonal, and inflammatory mechanisms, and atherosclerotic degeneration. In the process of better understanding the bi-directional pathophysiological aspects of CRS, the need to find precise and easy-to-use markers has also evolved. Based on the new pathophysiological standpoints and an overall vision of the CRS, the literature on renal, cardiac, metabolic, oxidative, and vascular circulating biomarkers was evaluated. Though the effectiveness of different extensively applied biomarkers remains controversial, evidence for several indicators, particularly when combined, has increased in recent years. From new aspects of classic biomarkers to microRNAs, this review aimed at a 360-degree analysis of the pathways that balance the kidney and the heart physiologies. In this delicate system, different markers and their combination can shed light on the diagnosis, risk, and prognosis of CRS.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset T2DM are recorded in China (520 cases/100,000) and in the United States (212 cases/100,000), and the numbers are still increasing. T2DM young people present a strong hereditary component, often unmasked by social and environmental risk factors. These patients are affected by multiple coexisting risk factors, including obesity, hyperglycemia, dyslipidemia, insulin resistance, hypertension, and inflammation. Juvenile T2DM nephropathy occurs earlier in life compared to T1DM-related nephropathy in children or T2DM-related nephropathy in adult. Diabetic kidney disease (DKD) is T2DM major long term microvascular complication. This review summarizes the main mechanisms involved in the pathogenesis of the DKD in young population and the recent evolution of treatment, in order to reduce the risk of DKD progression.

Among the 17 Sustainable Development Goals (SDGs) that make up the 2030 Agenda and refer to different areas of social, economic and environmental development, goal 11.2 concerns access to safe, cheap, accessible and sustainable transport systems, increasing road safety particularly through the enhancement of public transport. Universities can also contribute to increasing the use of more sustainable means of transport through policies and strategies to encourage students and staff in choosing sustainable transport modes. Numerous universities around the world and in Italy have adopted initiatives to reduce the environmental impact related to the mobility of the entire academic community. In Italy, the Italian Network of Sustainable Universities has set up, within its organization, a working group that has drawn up numerous studies on the sustainable mobility of Italian universities. The University of Foggia also conducted a study on mobility to detect and evaluate the mobility routines of community members (students, academic and administrative staff). In this paper, the first results in terms of descriptive analysis are shown. We submitted a survey consisting of 17 questions, and we obtained 3495 answers. After cleaning the data set, we were able to extract various contingency tables, through which we can statistically describe the main means of transport used by members of the University of Foggia community and, thanks to detailed data about the different means of transport, we can estimate their emissions. According to the results shown in the paper, further considerations could be made concerning the environmental implications of the choices of transportation modes. This could address policies about mobility at universities and provide useful information for applying actions to enhance these sustainable choices.

Diabetes mellitus represents a growing concern, both for public economy and global health. In fact, it can lead to insidious macrovascular and microvascular complications, impacting negatively on patients’ quality of life. Diabetic patients often present diabetic kidney disease (DKD), a burdensome complication that can be silent for years. The average time of onset of kidney impairment in diabetic patients is about 7–10 years. The clinical impact of DKD is dangerous not only for the risk of progression to end-stage renal disease and therefore to renal replacement therapies, but also because of the associated increase in cardiovascular events. An early recognition of risk factors for DKD progression can be decisive in decreasing morbidity and mortality. DKD presents patient-related, clinician-related, and system-related issues. All these problems are translated into therapeutic inertia, which is defined as the failure to initiate or intensify therapy on time according to evidence-based clinical guidelines. Therapeutic inertia can be resolved by a multidisciplinary pool of healthcare experts. The timing of intensification of treatment, the transition to the best therapy, and dietetic strategies must be provided by a multidisciplinary team, driving the patients to the glycemic target and delaying or overcoming DKD-related complications. A timely nephrological evaluation can also guarantee adequate information to choose the right renal replacement therapy at the right time in case of renal impairment progression.

Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20–30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed “diabetic kidney disease” without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy.

Diabetic kidney disease (DKD) is one of the most serious complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Current guidelines recommend a personalized approach in order to reduce the burden of DM and its complications. Recognizing sex and gender- differences in medicine is considered one of the first steps toward personalized medicine, but the gender issue in DM has been scarcely explored so far. Gender differences have been reported in the incidence and the prevalence of DKD, in its phenotypes and clinical manifestations, as well as in several risk factors, with a different impact in the two genders. Hormonal factors, especially estrogen loss, play a significant role in explaining these differences. Additionally, the impact of sex chromosomes as well as the influence of gene–sex interactions with several susceptibility genes for DKD have been investigated. In spite of the increasing evidence that sex and gender should be included in the evaluation of DKD, several open issues remain uncovered, including the potentially different effects of newly recommended drugs, such as SGLT2i and GLP1Ras. This narrative review explored current evidence on sex/gender differences in DKD, taking into account hormonal, genetic and clinical factors.

Vitamin D modulates bisphosphonate (BP) efficacy, but its contribution to bone mineral density (BMD) after BP discontinuation is not known. To address this topic, we performed a retrospective analysis of postmenopausal women exposed to alendronate (ALN) to treat osteoporosis who regularly continued the supplementation of cholecalciferol or calcifediol at recommended doses. In the ninety-six recruited women (age 61.1 ± 6.9 years), ALN was administered for 31.2 ± 20.6 months and then discontinued for 33.3 ± 18.9 months. The modification of 25(OH)D serum levels over time was associated with a change of alkaline phosphatase (r = −0.22, p = 0.018) and C-terminal collagen type 1 telopeptide (r = −0.3, p = 0.06). Women in the tertile of the highest increase in 25(OH)D level showed a 5.7% BMD gain at lumbar spine, that was twice as great in comparison with participants with a lower 25(OH)D variation. At a multiple regression analysis, BMD change was associated with time since menopause (ß = 2.28, SE 0.44, p < 0.0001), FRAX score for major fracture (ß = −0.65, SE 0.29, p = 0.03), drug holiday duration (ß = −2.17, SE 0.27, p < 0.0001) and change of 25(OH)D levels (ß = 0.15, SE 0.03, p = 0.0007). After ALN discontinuation, improving the vitamin D status boosts the ALN tail effect on BMD.

Dense deposit disease or membranoproliferative glomerulonephritis type II is a rare glomerulopathy characterized on renal biopsy by deposition of abnormal electron-dense material in the glomerular basement membrane. The pathophysiologic basis is uncontrolled systemic activation of the alternate pathway of the complement cascade. C3 nephritic factor, an autoantibody directed against the C3 convertase of the alternate pathway, plays a key role. In some patients, complement gene mutations have been identified. We report the case of a child who had persistent microscopic hematuria, proteinuria, and hypocomplementemia C3 for over 2 months. Renal biopsy confirmed the diagnosis of dense deposit disease.

The spectrum of lipid disorders in chronic kidney disease (CKD) is usually characterized by high triglycerides and reduced high dense lipoprotein (HDL), associated with normal or slightly reduced low dense lipoprotein (LDL)-cholesterol. This dyslipidemia is associated with an increased risk for atherosclerotic cardiovascular disease. Keys for the cardiovascular risk reduction in these patients are lowering the number and modifying the composition of the cholesterol-carrying atherogenic lipoprotein particles. Statins have an important role in primary prevention of cardiovascular events and mortality in non-hemodialyzed CKD patients. The benefits in terms of progression of renal failure are contradictory. Patient education regarding dietary regimen should be part of the CKD clinical management.

Previously, we showed that mesenchymal stem cells (MSC) can be mobilized into peripheral blood using electroacupuncture (EA) at acupoints, LI-4, LI-11, GV-14, and GV-20. The purpose of this study was to determine whether EA-mobilized MSC could be harvested and expanded in vitro to be used as an autologous cell therapy in horses. Peripheral blood mononuclear cells (PBMC) isolated from young and aged lame horses (n = 29) showed a marked enrichment for MSCs. MSC were expanded in vitro (n = 25) and administered intravenously at a dose of 50 x 106 (n = 24). Treatment resulted in significant improvement in lameness as assessed by the American Association of Equine Practitioners (AAEP) lameness scale (n = 23). MSCs exhibited immunomodulatory function by inhibition of lymphocyte proliferation and induction of IL-10. Intradermal testing showed no immediate or delayed immune reactions to MSC (1 x 106 to 1 x 104). In this study, we demonstrated an efficient, safe and reproducible method to mobilize and expand, in vitro, MSCs in sufficiently high concentrations for therapeutic administration. We confirm the immunomodulatory function of these cells in vitro. This non-pharmacological and non-surgical strategy for stem cell harvest has a broad range of biomedical applications and represents an improved clinically translatable and economical cell source for humans.

Background: No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. Methods: We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). Results: We studied 562 patients (age 66.2 ± 14.5 y; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2, RAASI 76.2%). HK was “absent” in 50.7%, “resolving” in 15.6%, “new onset” in 16.6%, and “persistent” in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p < 0.0001), K-binders (from 2.0 to 7.7%, p < 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p < 0.001); these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR < 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). Conclusions: This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs.

Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeostasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease (CKD) patients, Vitamin D function is impaired; the renal hydrolyzation of its inactive form by the action of 1α-hydroxylase declines at the same pace of reduced nephron mass. Moreover, Vitamin D major carrier, the D-binding protein (DBP), is less represented due to Nephrotic Syndrome (NS), proteinuria, and the alteration of the cubilin–megalin–amnionless receptor complex in the renal proximal tubule. In Glomerulonephritis (GN), Vitamin D supplementation demonstrated to significantly reduce proteinuria and to slow kidney disease progression. It also has potent antiproliferative and immunomodulating functions, contributing to the inhibitions of kidney inflammation. Vitamin D preserves the structural integrity of the slit diaphragm guaranteeing protective effects on podocytes. Activated Vitamin D has been demonstrated to potentiate the antiproteinuric effect of RAAS inhibitors in IgA nephropathy and Lupus Nephritis, enforcing its role in the treatment of glomerulonephritis: calcitriol treatment, through Vitamin D receptor (VDR) action, can regulate the heparanase promoter activity and modulate the urokinase receptor (uPAR), guaranteeing podocyte preservation. It also controls the podocyte distribution by modulating mRNA synthesis and protein expression of nephrin and podocin. Maxalcalcitol is another promising alternative: it has about 1/600 affinity to vitamin D binding protein (DBP), compared to Calcitriol, overcoming the risk of hypercalcemia, hyperphosphatemia and calcifications, and it circulates principally in unbound form with easier availability for target tissues. Doxercalciferol, as well as paricalcitol, showed a lower incidence of hypercalcemia and hypercalciuria than Calcitriol. Paricalcitol demonstrated a significant role in suppressing RAAS genes expression: it significantly decreases angiotensinogen, renin, renin receptors, and vascular endothelial growth factor (VEGF) mRNA levels, thus reducing proteinuria and renal damage. The purpose of this article is to establish the Vitamin D role on immunomodulation, inflammatory and autoimmune processes in GN.

An amendment to this paper has been published and can be accessed via the original article.