Transitioning to peritoneal dialysis: it does not matter where you come from.

INTRODUCTION: Patients with end-stage renal disease (ESRD) frequently change renal replacement (RRT) therapy modality due to medical or social reasons. We aimed to evaluate the outcomes of patients under peritoneal dialysis (PD) according to the preceding RRT modality. METHODS: We conducted a retrospective observational single-center study in prevalent PD patients from January 1, 2010, to December 31, 2017, who were followed for 60 months or until they dropped out of PD. Patients were divided into three groups according to the preceding RRT: prior hemodialysis (HD), failed kidney transplant (KT), and PD-first. RESULTS: Among 152 patients, 115 were PD-first, 22 transitioned from HD, and 15 from a failing KT. There was a tendency for ultrafiltration failure to occur more in patients transitioning from HD (27.3% vs. 9.6% vs. 6.7%, p = 0.07). Residual renal function was better preserved in the group with no prior RRT (p < 0.001). A tendency towards a higher annual rate of peritonitis was observed in the prior KT group (0.70 peritonitis/year per patient vs. 0.10 vs. 0.21, p = 0.065). Thirteen patients (8.6%) had a major cardiovascular event, 5 of those had been transferred from a failing KT (p = 0.004). There were no differences between PD-first, prior KT, and prior HD in terms of death and technique survival (p = 0.195 and p = 0.917, respectively) and PD efficacy was adequate in all groups. CONCLUSIONS: PD is a suitable option for ESRD patients regardless of the previous RRT and should be offered to patients according to their clinical and social status and preferences.

Effect of overexpression of partial TDH1 and TDH2/3 gene sequences in a starter strain of industrial bioethanol fermentation on the Brettanomyces bruxellensis contaminant growth.

Selected Saccharomyces cerevisiae strains, such as the commercial Ethanol-Red (ER) strain, are used as starters in the bioethanol industry. Yet, bioethanol fermentations are prone to microbial contaminations, mainly by Brettanomyces bruxellensis and lactic acid bacteria. Chemicals, such as sulphuric acid and antibiotics, are commonly used to combat those contaminations, but they have negative environmental impacts. Recently, ER strain was found to secrete antimicrobial peptides (AMPs) active against B. bruxellensis. Therefore, the partial TDH1 and TDH2/3 genes sequences that codify those AMPs were inserted into the pSR41k plasmid and cloned in ER strains. The relative expression levels (plasmidic/genomic) of those sequences in the respective modified ER strains were quantified by real-time quantitative polimerase chain reaction (RT-qPCR), confirming their overexpression. The effect of the modified strains on B. bruxellensis (Bb) growth was then evaluated during synthetic must (SM) and carob syrup (CS) fermentations, co-inoculated with 105 cells ml-1 of ER and Bb in SM and with 106 of ER and 5 × 103 cells ml-1 of Bb in CS. Results showed that modified ER strains exerted a much higher inhibitory effect against B. bruxellensis (72-fold in SM and 10-fold in CS) than the non-modified ER strain. In those fermentations, 90-100 g l-1 of ethanol was produced in 3-6 days.

Exploring the Multifaceted Potential of a Peptide Fraction Derived from Saccharomyces cerevisiae Metabolism: Antimicrobial, Antioxidant, Antidiabetic, and Anti-Inflammatory Properties.

The rising demand for minimally processed, natural, and healthier food products has led to the search for alternative and multifunctional bioactive food components. Therefore, the present study focuses on the functional proprieties of a peptide fraction derived from Saccharomyces cerevisiae metabolism. The antimicrobial activity of the peptide fraction is evaluated against various foodborne pathogens, including Candida albicans, Candida krusei, Escherichia coli, Listeria monocytogenes, and Salmonella sp. The peptide fraction antioxidant properties are assessed using FRAP and DPPH scavenging capacity assays. Furthermore, the peptide fraction's cytotoxicity is evaluated in colorectal carcinoma and normal colon epithelial cells while its potential as an antidiabetic agent is investigated through α-amylase and α-glucosidase inhibitory assays. The results demonstrate that the 2-10 kDa peptide fraction exhibits antimicrobial effects against all tested microorganisms, except C. krusei. The minimal inhibitory concentration for E. coli, L. monocytogenes, and Salmonella sp. remains consistently low, at 0.25 mg/mL, while C. albicans requires a higher concentration of 1.0 mg/mL. Furthermore, the peptide fraction displays antioxidant activity, as evidenced by DPPH radical scavenging activity of 81.03%, and FRAP values of 1042.50 ± 32.5 µM TE/mL at 1.0 mg/mL. The peptide fraction exhibits no cytotoxicity in both tumor and non-tumoral human cells at a concentration up to 0.3 mg/mL. Moreover, the peptide fraction presents anti-inflammatory activity, significantly reducing the expression of the TNFα gene by more than 29.7% in non-stimulated colon cells and by 50% in lipopolysaccharide-stimulated colon cells. It also inhibits the activity of the carbohydrate digestive enzymes α-amylase (IC50 of 199.3 ± 0.9 µg/mL) and α-glucosidase (IC20 of 270.6 ± 6.0 µg/mL). Overall, the findings showed that the peptide fraction exhibits antibacterial, antioxidant, anti-inflammatory, and antidiabetic activity. This study represents a step forward in the evaluation of the functional biological properties of S. cerevisiae bioactive peptides.

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis.

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.

Diuretic-resistant heart failure and the role of ultrafiltration: A proposed protocol.

Acute heart failure (HF) decompensation generally manifests with signs and symptoms of congestion that strongly predict poor poor patient outcome. Loop diuretics are the cornerstone of therapy to counteract fluid overload and are widely used for acute management and chronic stabilization of HF. However, a diminished response to loop diuretics is a common problem, affecting the patient's clinical course and potentially prolonging hospitalization. Diuretic resistance is defined as failure to decongest despite appropriate and escalating loop diuretic therapy. We propose a protocol for the management of diuretic resistance. The initial approach should include an assessment of causes of pseudo-diuretic resistance. Adjustments to loop diuretic therapy, such as increasing doses and frequency of administration and sequential nephron blockade, may be successful. For hospitalized patients with progressive disease there are more invasive methods for fluid removal. Switching from oral to intravenous loop diuretics is essential to avoid variable absorption and for symptomatic relief. Extracorporeal ultrafiltration is also an option since this technique is highly effective at removing plasma fluid from blood. While extracorporeal ultrafiltration is an invasive solution, peritoneal dialysis is a home-based, intermittent therapeutic option that can enable efficient management of fluid overload, preventing HF-related hospital admission, and improving quality of life. As a last resort for fluid removal, a peritoneal dialysis regimen should fully exploit its decongestive properties and should be tailored to the patient's characteristics and clinical needs.

Co-Administration of Albumin and Furosemide in Acute Heart Failure with Diuretics Resistance.

Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute heart failure are caused by congestive conditions, not all patients have a congestive phenotype, reflecting the complexity of a process with multiple pathophysiological pathways. The use of diuretics, usually loop diuretics, is the mainstay of treatment for congestion. However, many patients develop resistance, thus constituting a challenge with no consensual solution to date, despite extensive debate over the years. Despite its frequent use in clinical practice, the co-administration of albumin and furosemide remains controversial in the management of patients with acute heart failure, hypoalbuminemia, and diuretic resistance. This review addresses the pathophysiological mechanisms of congestion in patients with acute heart failure and explores the theoretical basis that supports the co-administration of albumin and furosemide in this clinical context. It is intended to clarify the potential benefit of the combined approach in this specific population and identify possible gaps in the literature that could be the subject of future studies.

Incremental Peritoneal Dialysis-Definition, Prescription, and Clinical Outcomes.

ABSTRACT: Incremental peritoneal dialysis (IPD) is a strategy of RRT that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis (PD). The clearance goals are achieved through the combination of residual kidney function (RKF) and peritoneal clearance. The dialysis prescription should be increased as the RKF declines. IPD has been associated with clinical, economic, and environmental advantages. We emphasize possible better quality of life, fewer mechanical symptoms, lower costs, slight adverse metabolic effects, and less plastic waste and water consumption. The potential benefits for RKF preservation and the lower risk of peritonitis have also been discussed. There are some concerns regarding this strategy, such as inadequate clearance of uremic toxins and/or severe electrolyte disturbances due to undetected loss of RKF, lower clearance of medium-sized molecules (such as ß-2-microglobulin) which mostly depends on the total PD dwell time, and patients' reluctance to dose adjustments. Current clinical evidence is based on moderate-quality to low-quality studies and suggests that the outcomes of IPD will be at least identical to those of full dose. This review aims to define IDP, discuss strategies for prescription, and review its advantages and disadvantages according to the current evidence.

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

INTRODUCTION: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal. METHODS: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols. RESULTS: In 2017 and 2018, 14 Portuguese units followed 764 and 689 patients. ESi incidence rate was 0.41 episodes/year, and the peritonitis incidence rate was 0.37. All units monitor catheter-related infections on a yearly basis, use antibiotic prophylaxis at the time of catheter placement, and treat nasal carriage of S. aureus, although with different approaches. Screening for nasal carriage of S. aureus is performed by 12 units, and daily topical antibiotic cream is recommended by 6 out of 14 of the units. We did not find statistical differences in ESi/peritonitis, comparing these practices. The rate of ESis was lower with nonocclusive dressing immediately after catheter insertion, bathing without ES dressing, with the use of colostomy bags in beach baths and was higher with the use of bath sponge. The peritonitis rate was lower with bathing without ES dressing and if shaving of the external cuff was performed in the presence of chronic ESi. CONCLUSIONS: We found potential proceedings associated with ESi and peritonitis. A regular national audit of peritoneal dialysis units is an important tool for clarifying the best procedures for reduction of catheter-related infections.

Membranous nephropathy after a recent SARS-CoV-2 infection.

SARS-CoV-2 infections can induce kidney injury and glomerulopathy, with the most common pathology findings being acute tubular injury and collapsing glomerulopathy.Here we describe a rare case of membranous nephropathy in a man in his late 70s presented with nephrotic syndrome and rapidly progressive kidney dysfunction 1 month after SARS-CoV-2 infection. Phospholipase A2 receptor antibodies were positive. He was treated with rituximab, with proteinuria control. We review the cases reported in the literature.

Incremental peritoneal dialysis: Is it better for preservation of residual kidney function and clinical outcomes?

INTRODUCTION: Incremental peritoneal dialysis (IPD) is based on the prescription of a dose lower than the standard (SPD). The combination of residual kidney function (RKF) and peritoneal clearance achieves clearance goals. The aim of this study is to compare the outcomes of IPD with SPD. MATERIALS AND METHODS: This was a single-center, retrospective study that included a cohort of prevalent peritoneal dialysis (PD) adults. Patients were assigned according to their first PD protocol in two groups - group A: IPD protocol (continuous ambulatory PD: less than 4 dwells daily, less than 2 L dwell volume, and/or treatment less than 7 days/week; automated PD: without a long dwell, less than 10 L daily delivered, and/or treatment for less than 7 days/week); group B: SPD protocol. RESULTS: 87 PD patients were included, 65.5% underwent IPD. The median follow-up time was 23 months (IQR 15 - 35). IPD had a higher glomerular filtration ratio (7 vs. 3.7, mL/min/1.73m2, p < 0.001) in the first 6 months, and after 24 months (4.8 vs. 1.9, mL/min/1.73m2, p = 0.002). IPD protocol was independently associated with GFR ≥ 5 mL/min/1.73m2 at 24 months (OR 13 per point, 95% CI 1.48 - 114.36, p = 0.021). IPD was also associated with a longer technique survival (log-rank test = 4.928, p = 0.026), lower hospital admissions per year (0.23 vs. 0.5, p = 0.001), and lower mortality (1.8% vs. 13.3%, p = 0.027). Cox regression demonstrated that IPD (HR 0.30; 95% CI 0.098 - 0.93); p = 0.036) was associated with a decrease in the risk of technique failure. CONCLUSION: The prescription of IPD seems to be beneficial, in terms of outcomes, for patients with substantial RKF.

Alpha-klotho and peritoneal membrane status: A hypothesis generating study.

BACKGROUND: Long-term success of peritoneal dialysis relies on the integrity of the peritoneal membrane. This proof-of-concept study addressed the hypothesis that fibrosis is already present in the membrane at pre-dialysis and that the membrane status is related to the individual's uraemic fingerprint. METHODS: A clinical-mechanistic, transversal, single-centre study was conducted. Pre-dialysis peritoneal biopsies were scored considering the submesothelial compact zone thickness (STM), vasculopathy and inflammation. We investigated if the membrane status could be inferred from a panel of proteins (α-Klotho, Galectin-3, FGF21, FGF23, Tweak, TNFα and hsPCR) in blood. RESULTS: A total 58 incident patients aged 56 ± 15 years old were included, 31% female, 55% hypertension, 29% diabetic and 24% obese. Person-to-person STM was found to be highly variable and 38% of patients were fibrosis positive. Both α-Klotho (Spearman r = -.7491, p < 0.001) and FGF21 (Spearman r = -.5102, p < 0.001) were negatively associated with STM. α-Klotho, but not FGF21, was able to discriminate fibrosis from nonfibrosis with/without inflammation and vasculopathy. PLS models identified α-Klotho as the protein most relevant for fibrosis. α-Klotho was independently associated with fibrosis of the peritoneal membrane (OR = .991 (.896-.997), p = 0.002). CONCLUSION: Before the start of dialysis in incident patients, some patients already present fibrosis of the peritoneal membrane and other patients do not. Our findings suggest that α-Klotho may be implicated in fibrosis of the peritoneal membrane.

'If I hadn't seen this picture, I'd be smoking'-perceptions about innovations in health warnings for cigarette packages in Brazil: a focus group study.

OBJECTIVE: To investigate the perceptions of young people and adults, smokers and non-smokers about the current set of innovations introduced in 2018 into the Brazilian tobacco products' health warnings. METHODS: Twenty focus groups were conducted in five state capitals in Brazil. The participants (n=163) were segmented by smoking status, age (15-17 years, 18-55 years) and social grade (C, D-E classes) to examine cigarette packaging and explore the participants' perceptions of health warnings. RESULTS: Health warnings capture attention, eliciting apprehension, fear, disgust and concern about the negative consequences of cigarette consumption. The 2018 Brazil health warnings are spontaneously recalled by participants, even without the presence of cigarette packages. However, the analysis also reveals the challenges of overcoming communication barriers and distorted interpretations, especially among smokers. The inclusion of direct and provocative stimuli, such as the use of the word 'you', attracts attention and creates more proximity to the recipient of the message. The results also highlight the interest and fear elicited by warnings on toxic constituents and the importance of using contrasting colours in warnings, which differentiate them from the colours of cigarette packs. CONCLUSION: Introducing innovative components in health warnings can catch consumers' attention but considering that the interviewees encountered difficulties interpreting textual warnings about toxic constituents in cigarettes, the study reinforces the importance of adopting direct language and pictures, instead of text, which can visually transmit the warning messages and the use of specific wording that generates proximity between the emitter and receiver.

Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines.

Notwithstanding the advances in molecular target-based drugs, chemotherapy remains the most common cancer treatment, despite its high toxicity. Consequently, effective anticancer therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa) tumor cells, as well as non-tumor cells (PNT2), using sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between albumin and each rare flavonoid, supporting the impact of fetal bovine serum in DCMF antitumor activity. The IC50 values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to tumor or normal cells when exposed to twice the IC50 for up to 24 h, but it inhibited tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in tumor cell membranes while having fewer toxicological effects on normal cells.

Pantoea in Peritoneal Dialysis: A Rare Cause of Peritonitis.

Peritonitis is the most common complication of peritoneal dialysis (PD) and an important cause of PD failure. There are numerous etiological agents, mostly bacteria. Pantoea spp is a rare cause of peritonitis. We describe three cases of Pantoea peritonitis in three PD patients. Previous reports have identified risk factors such as close contact with plants and animals. We review the typical clinical presentation and prognosis. It is fulcral to teach patients about the risks regarding proximity to plants and animals to prevent this type of infection.

Mutational Signature and Integrative Genomic Analysis of Human Papillomavirus-Associated Penile Squamous Cell Carcinomas from Latin American Patients.

High-throughput DNA sequencing has allowed for the identification of genomic alterations and their impact on tumor development, progression, and therapeutic responses. In PSCC, for which the incidence has progressively increased worldwide, there are still limited data on the molecular mechanisms involved in the disease pathogenesis. In this study, we characterized the mutational signature of 30 human papillomavirus (HPV)-associated PSCC cases from Latin Americans, using whole-exome sequencing. Copy number variations (CNVs) were also identified and compared to previous array-generated data. Enrichment analyses were performed to reveal disrupted pathways and to identify alterations mapped to HPV integration sites (HPVis) and miRNA-mRNA hybridization regions. Among the most frequently mutated genes were NOTCH1, TERT, TTN, FAT1, TP53, CDKN2A, RYR2, CASP8, FBXW7, HMCN2, and ITGA8. Of note, 92% of these altered genes were localized at HPVis. We also found mutations in ten novel genes (KMT2C, SMARCA4, PTPRB, AJUBA, CR1, KMT2D, NBEA, FAM135B, GTF2I, and CIC), thus increasing our understanding of the potential HPV-disrupted pathways. Therefore, our study reveals innovative targets with potential therapeutic benefits for HPV-associated PSCCs. The CNV analysis by sequencing (CNV-seq) revealed five cancer-associated genes as the most frequent with gains (NOTCH1, MYC, NUMA1, PLAG1, and RAD21), while 30% of the tumors showed SMARCA4 with loss. Additionally, four cancer-associated genes (CARD11, CSMD3, KDR, and TLX3) carried untranslated regions (UTRs) variants, which may impact gene regulation by affecting the miRNAs hybridization regions. Altogether, these data contribute to the characterization of the mutational spectrum and its impact on cellular signaling pathways in PSCC, thus reinforcing the pivotal role of HPV infection in the molecular pathogenesis of these tumors.

Pregnancy in a woman undergoing peritoneal dialysis: Management and dialysis options.

Pregnancy in patients with end-stage renal disease on maintenance dialysis is uncommon, with annual incidences reported at 0.3 - 2.7%. Peritoneal dialysis usage in pregnancy has been less reported than hemodialysis, although outcomes are similar. Nowadays, there are insufficient data to establish a generalizable dialysis strategy in pregnant women with end-stage renal disease. As such, decisions should be individualized, depending on clinical factors, residual renal function, and, whenever possible, choice of the patient. We report the case of a 22-year-old patient receiving peritoneal dialysis who delivered a full-term, normal weight, healthy baby with increased dialysis dose achieved by supplementary hemodialysis during pregnancy, thus enabling peritoneal dialysis to be continued until the third trimester and minimizing hemodialysis requirements.

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine.

In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.

Wine Spoilage Control: Impact of Saccharomycin on Brettanomyces bruxellensis and Its Conjugated Effect with Sulfur Dioxide.

The yeast Brettanomyces bruxellensis is one of the most dangerous wine contaminants due to the production of phenolic off-flavors such as 4-ethylphenol. This microbial hazard is regularly tackled by addition of sulfur dioxide (SO2). Nevertheless, B. bruxellensis is frequently found at low levels (ca 103 cells/mL) in finished wines. Besides, consumers health concerns regarding the use of sulfur dioxide encouraged the search for alternative biocontrol measures. Recently, we found that Saccharomyces cerevisiae secretes a natural biocide (saccharomycin) that inhibits the growth of different B. bruxellensis strains during alcoholic fermentation. Here we investigated the ability of S. cerevisiae CCMI 885 to prevent B. bruxellensis ISA 2211 growth and 4-ethylphenol production in synthetic and true grape must fermentations. Results showed that B. bruxellensis growth and 4-ethylphenol production was significantly inhibited in both media, although the effect was more pronounced in synthetic grape must. The natural biocide was added to a simulated wine inoculated with 5 × 102 cells/mL of B. bruxellensis, which led to loss of culturability and viability (100% dead cells at day-12). The conjugated effect of saccharomycin with SO2 was evaluated in simulated wines at 10, 12, 13 and 14% (v/v) ethanol. Results showed that B. bruxellensis proliferation in wines at 13 and 14% (v/v) ethanol was completely prevented by addition of 1.0 mg/mL of saccharomycin with 25 mg/L of SO2, thus allowing to significantly reduce the SO2 levels commonly used in wines (150-200 mg/L).

Peritoneal dialysis-associated peritonitis caused by Enterococcus avium.

Peritonitis remains a common and serious complication of peritoneal dialysis. Peritonitis caused by gram-positive organisms includes coagulase-negative staphylococci, Streptococcus spp and Enterococcus spp. We present a rare case of peritoneal dialysis-associated peritonitis, where persisting abdominal pain and worsening laboratory findings despite antibiotic therapy led to the identification of Enterococcus avium, requiring Tenckoff catheter removal and temporary transfer to haemodialysis. The available literature reports only few cases where peritonitis is caused by this agent, underlining the need to consider atypical microbial agents when heterogeneous clinical course is presented.