The water channel Aquaporin 1 (AQP1) plays a fundamental role in water ultrafiltration during peritoneal dialysis (PD) and its reduced expression or function may be responsible for ultrafiltration failure (UFF). In humans, AQP1 is expressed in the endothelium of the peritoneal capillaries but its expression in mesothelial cells (MC) and its functional role in PD is still being debated. Here, we studied a cohort of 30 patients using PD in order to determine the presence of AQP1 in peritoneal biopsies, AQP1 release in the PD effluent through exosomes and the correlation of AQP1 abundance with the efficiency of peritoneal ultrafiltration. The experiments using immunofluorescence showed a strong expression of AQP1 in MCs. Immunoblotting analysis on vesicles isolated from PD effluents showed a consistent presence of AQP1, mesothelin and Alix and the absence of the CD31. Thus, this suggests that they have an exclusive mesothelial origin. The immunoTEM analysis showed a homogeneous population of nanovesicles and confirmed the immunoblotting results. Interestingly, the quantitative analysis by ELISA showed a positive correlation between AQP1 in the PD effluent and ultrafiltration (UF), free water transport (FWT) and Na-sieving. This evidence opens the discussion on the functional role of mesothelial AQP1 during PD and suggests that it may represent a potential non-invasive biomarker of peritoneal barrier integrity, with predictive potential of UFF in PD patients.
Proteolytic dysbiosis of the gut microbiota has been recognized as both a typical feature of chronic kidney disease (CKD) and a risk factor for its progression. Blood accumulation of gut-derived uremic toxins (UTs) like indoxyl sulfate (IS) and p-cresyl sulfate (PCS), intestinal permeability and constipation are typical features accompanying CKD progression and triggering chronic inflammation. In order to verify the efficacy of the innovative synbiotic formulation NATUREN G® in modulating the levels of circulating UTs, intestinal permeability and gastrointestinal symptoms, we set up a randomized, single-blind, placebo-controlled, pilot trial in stage IIIb-IV CKD patients and in healthy controls. Two-month administration of the synbiotic resulted in a decrease of free IS, as compared with the placebo-treated arm, only in the CKD group. The other UTs did not significantly change, although different trends in time (increase in the placebo arm and decrease in the synbiotic arm) were observed. Moreover, after supplementation, reduction of small intestinal permeability and amelioration of abdominal pain and constipation syndromes were observed only in the CKD group. The obtained results suggest the specificity of action of NATUREN G® in CKD and justify further validation in a wider study population.
Background and Aims Over 2 million persons of the 7.8 billion world population undergo hemodialysis (HD). The need is underestimated because dialysis is not available free of charge for more of half of the word population. HD is costly process and produces a large quantity of medical waste. Reducing the environmental burden should be addressed as part of implementation dialysis programs. While collaboration between physicians and several different professionals is needed to design and develop projects in this direction, these are lingering and the literature is still scant. We overviewed literature to frame what is in progress and find clues for development. Method We conducted a systematic review of the literature from 2000 searching in PubMed, Scopus, Web of Science, and Google Scholar using search keywords including dialysis, green, recycling, ecology. We retrieved 41 publications in medical and technological fields. The results were summarized in a narrative review. Results Facilities: the points on which attention is focused are the design of new buildings, whose project should encompass green solutions, including solar power and water conservation, to reduce long-term expenses and ensure an eco-friendly development. Water: water consumption remains high, and the essential targets to improve efficiency are the optimization of the reverse osmosis system, and of the dialysate flow rate, and the waste-water management. The current idea is to substitute standard reverse osmosis, which have a high percent of waste-water, with recirculating systems. Likewise, lowering of dialysate flow rate could spare water consumption with no significant difference in term of efficiency. Moreover, different solutions have been proposed to reuse reject water: local sanitation, laundry departments, sterilization units within health facilities using redirected water, landscaping and irrigation. Power: electricity needed per dialysis session is twice the average daily consumption of a family of four people. Use of renewable energies, as solar or wind power, has been proposed, and are occasionally applied to home HD. To date just one attempt has been made to recycling energy by using hydroturbine. Disposable materials: most of dialysis disposables is made of plastic, over half of which is labeled as “potentially hazardous”. Only a minimal part of the plastic used in dialysis disposables is recyclable, both because of its composition and its assembly which makes in fact impossible the segregation of the different components. Present research regards bioplastics, new assembling techniques, alternative technologies of incineration, microwave treatment, alkaline hydrolysis, biological treatment and the new steam sterilize-then-shred system. Dialysis machines: at the best of our knowledge there are no studies available about dialysis machine recycling. Personnel education: the role of dialysis staff is essential in recycling and reusing materials as well as in correctly dividing contaminated and non-contaminated waste. Conclusion The development of sustainable buildings, devices and procedures requires a multidisciplinary approach: medical, chemical, biological, engineering; in addition producers contribution and government regulation are needed. Talking about these issues, involving specialists, spreading the concepts of planet friendly treatments, gives the opportunity to share ideas, experiences and turn them into relevant innovations. A good starting point could be data collection to identify critical issues and outline pragmatic operational possibilities to reduce consumption, increase reuse and recycle, involve and instruct health care personnel, integrate dialysis facilities in the environment they are built in.
Background and Aims Etelcalcetide is an injectable calcimimetic, utilized to treat secondary hyperparathyroidism. Recently introduced as alternative to cinacalcet, it acts on a different CaSR (Calcium Sensor Receptor) binding site. Outlined advantages are the intravenous formulation, which solves non adherence, the lower gastrointestinal side effects incidence. The main limitation is iatrogenic hypocalcemia. We show our experience to evaluate findings of our initial fieldwork in order to optimize drug efficacy, safety and tolerability Method We included 27 patients during 2018 (15 M and 12 F, Caucasian, mean age 60,7±13,7 years), followed for at least 6 months. Initial etelcalcetide dose was 15 mg in all patients. PTH, Calcium, Phosphorus monitoring was done every month. Concomitant drugs as phosphorus binders, Vitamin D or analogues, Calcium and the switch from cinacalcet were considered. Therapeutic variations and side effects were recorded. Data are registered at the beginning and the end of follow up. Results Starting values are: PTH 1298±545 pg/ml, Calcium 9,1±0,9, Phosphorus 5,1±1,4. 14 patients already took phosphorus binders, 10 paricalcitol. 12 patients were switched from Cinacalcet because of non-adherence or inefficacy, the other 15 patients never took calcimimetics. Mean values after 6 months are: PTH 661±469 pg/ml, Calcium 8,2±0,5 mg/ml, Phosphorus 4,1±1,6 mg/ml. These data point out a mean decrease in PTH value of 49%, reaching the therapeutic target in 18 patients, that is the 75% of the total population studied. It have been necessary dose modifications in 15 patients (62.5%): 9 etelcalcetide dose variations (37,5%), 6 vitamin D and Calcium supplementation, both the changes in 5 of them. Side effects were hypocalcemia (14), pruritus (1), diarrhea (1), low platelet count (1), registered in 17 patients (63%), 3 of them withdrew therapy and then refused to start it again. It has to be said that thrombocytopenia, occurred after the follow up time (at 7th month), solve after etelcacetide withdrawal. Subgroup analysis pointed out a statistically significant correlation between drug efficacy and switch from cinacalcet, both in terms of extent of iPTH reduction (65% vs 42% - p value < 0,05 ) and of achievement of the therapeutic target (89% vs 66% - p value < 0,05), and between concomitant paricalcitol therapy at zero-time and lower hypocalcemia incidence (10% vs 76% - p value < 0,05). Conclusion Results confirm etelcalcetide efficacy and suggest a correlation between concomitant paricalcitol therapy at baseline and lower hypocalcemia incidence and between greater efficacy and switch from cinacalcet. These data, if confirmed in larger sample, could be useful to guide the starting approach and the maintaining treatment with etelecalcetide.
Background and Aims Data about HD patients and how to best dialyze them during the COVID-19 pandemic are scarce. The aim of the study is to describe the organizational model and clinical outcomes of patients confirmed COVID-19 needing renal replacement therapy, admitted in a COVID Hospital in Southern Italy during the first and second pandemic wave. Method All the consecutive patients requiring chronic HD, during the first and second wave were considered. Due to local resources, we have implemented an organizational model based on the HD bedside with Genius system. The machine was prepared in the Dialysis Unit and then transferred to the COVID Hospital. After treatment, the monitor was sterilized and carefully cleaned with chlorine wipes and re-transferred into the dialysis Unit to be prepared for the next dialysis. Demographic data, clinical symptoms at presentation, and laboratory results were extracted by the electronic medical record. Patients hospitalized during the first wave (FW) and second wave (SW) were compared. Results From March 10 through December 31 2020, we enrolled a cohort of 40 patients (37.5% F), with COVID-19 infection requiring HD; 11 (27.5%) during first and 29 (72.5%) during second wave. The phenotype and clinical symptoms at the admission were not different between two groups. Compared to FW, the SW patients were younger (70.1±9.5 vs 77.3±5.9 years; p<0.03) with lower dialysis vintage (35±18 vs 60±48 months; p<0.05), and lower Charlson Comorbidity Index scores (2.8 ± 1.8 vs 5.09 ± 2.0; p<0.05). No differences were observed between the first and second wave as far as inflammatory markers IL6 (51.9 ± 44.8 vs 55.45 ± 40.52 pg/mL; ns) and C-reactive protein (4.74 ± 3.8 vs 6.70 ± 5.44 mg/L; ns) as well as the hospital stay (21.1±10 vs 24.4.8±10 days; ns) and in-hospital mortality (28.1% vs 18.2%; ns). Overall, 354 bedside treatments were performed; mean session time and mean weekly sessions were 3.64 ± 0.40 hours, and 3.4 ± 0.45 HD/week, with no differences between FW and SW patients. Conclusion Our data show that the higher spread of Sars-cov2 during the second wave has infected younger and less comorbid HD patients, with no significant differences in clinical and laboratory parameters. Our organizational model based on the HD bedside with the Genius system, allowed a personalized treatment with efficacy and safety for the patients and staff.
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