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15 pages, 1032 KiB  
Article
UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain
by Salvador Eduardo Acevedo-Monroy, Ulises Hernández-Chiñas, Luz María Rocha-Ramírez, Oscar Medina-Contreras, Osvaldo López-Díaz, Ricardo Ernesto Ahumada-Cota, Daniel Martínez-Gómez, Sara Huerta-Yepez, Ana Belén Tirado-Rodríguez, José Molina-López, Raúl Castro-Luna, Leonel Martínez-Cristóbal, Frida Elena Rojas-Castro, María Elena Chávez-Berrocal, Antonio Verdugo-Rodríguez and Carlos Alberto Eslava-Campos
Int. J. Mol. Sci. 2024, 25(18), 9876; https://doi.org/10.3390/ijms25189876 - 12 Sep 2024
Abstract
Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty [...] Read more.
Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials. Full article
11 pages, 740 KiB  
Article
Health Impacts of Pre-eclampsia: A Comprehensive Analysis of Maternal and Neonatal Outcomes
by Flavius George Socol, Elena Bernad, Marius Craina, Simona-Alina Abu-Awwad, Brenda-Cristiana Bernad, Ioana Denisa Socol, Ahmed Abu-Awwad, Simona Sorina Farcas, Daniel Laurențiu Pop, Daniela Gurgus and Nicoleta Ioana Andreescu
Medicina 2024, 60(9), 1486; https://doi.org/10.3390/medicina60091486 - 12 Sep 2024
Abstract
Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve [...] Read more.
Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve understanding of risk factors, diagnostic markers, and outcomes. Materials and Methods: This retrospective observational study involved 235 patients, 98 with pre-eclampsia and 137 without, monitored from 2015 to 2018 at the Obstetrics and Gynecology Department of the “Pius Brînzeu” Emergency County Clinical Hospital in Timișoara, Romania. Results: Women with pre-eclampsia were older, had higher BMIs, and more frequently had a family history of pre-eclampsia, hypertension, and diabetes. They also had lower educational and socioeconomic levels and fewer prenatal visits. Biochemical markers such as higher proteinuria, elevated sFlt-1, and lower PlGF were significant in diagnosing pre-eclampsia. Short-term maternal complications like eclampsia, HELLP syndrome, and acute kidney injury were more prevalent in the pre-eclampsia group. Neonatal outcomes included higher rates of preterm birth, low birth weight, and NICU admissions. Long-term mothers with a history of pre-eclampsia had higher incidences of chronic hypertension, cardiovascular disease, kidney problems, diabetes, and mental health disorders. Their children faced increased risks of neuropsychological delays, chronic respiratory issues, behavioral disorders, learning difficulties, and frequent infections. Conclusions: The study highlights the significant short- and long-term health impacts of pre-eclampsia on both mothers and their children. Early monitoring, intervention, and comprehensive management are crucial in mitigating these risks. These findings underscore the need for personalized care strategies to improve health outcomes for affected individuals. Full article
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21 pages, 763 KiB  
Review
The Role of the Gut Microbiota in Complications among Hemodialysis Patients
by Junxia Du, Xiaolin Zhao, Xiaonan Ding, Qiuxia Han, Yingjie Duan, Qinqin Ren, Haoran Wang, Chenwen Song, Xiaochen Wang, Dong Zhang and Hanyu Zhu
Microorganisms 2024, 12(9), 1878; https://doi.org/10.3390/microorganisms12091878 - 12 Sep 2024
Viewed by 197
Abstract
The composition of the gut microbiota varies among end-stage renal disease (ESRD) patients on the basis of their mode of renal replacement therapy (RRT), with notably more pronounced dysbiosis occurring in those undergoing hemodialysis (HD). Interventions such as dialysis catheters, unstable hemodynamics, strict [...] Read more.
The composition of the gut microbiota varies among end-stage renal disease (ESRD) patients on the basis of their mode of renal replacement therapy (RRT), with notably more pronounced dysbiosis occurring in those undergoing hemodialysis (HD). Interventions such as dialysis catheters, unstable hemodynamics, strict dietary restrictions, and pharmacotherapy significantly alter the intestinal microenvironment, thus disrupting the gut microbiota composition in HD patients. The gut microbiota may influence HD-related complications, including cardiovascular disease (CVD), infections, anemia, and malnutrition, through mechanisms such as bacterial translocation, immune regulation, and the production of gut microbial metabolites, thereby affecting both the quality of life and the prognosis of patients. This review focuses on alterations in the gut microbiota and its metabolites in HD patients. Additionally, understanding the impact of the gut microbiota on the complications of HD could provide insights into the development of novel treatment strategies to prevent or alleviate complications in HD patients. Full article
(This article belongs to the Section Medical Microbiology)
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11 pages, 528 KiB  
Review
Copper Serum Levels in the Hemodialysis Patient Population
by Guido Gembillo, Luigi Peritore, Vincenzo Labbozzetta, Alfio Edoardo Giuffrida, Antonella Lipari, Eugenia Spallino, Vincenzo Calabrese, Luca Visconti and Domenico Santoro
Medicina 2024, 60(9), 1484; https://doi.org/10.3390/medicina60091484 - 11 Sep 2024
Viewed by 232
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Urology & Nephrology)
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12 pages, 272 KiB  
Article
The Use of Kidney Biomarkers, Nephrin and KIM-1, for the Detection of Early Glomerular and Tubular Damage in Patients with Acromegaly: A Case–Control Pilot Study
by Iulia Stefania Plotuna, Melania Balas, Ioana Golu, Daniela Amzar, Roxana Popescu, Ligia Petrica, Adrian Vlad, Daniel Luches, Daliborca Cristina Vlad and Mihaela Vlad
Diseases 2024, 12(9), 211; https://doi.org/10.3390/diseases12090211 - 11 Sep 2024
Viewed by 202
Abstract
Background: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. [...] Read more.
Background: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. It is believed that high GH may also be involved in the onset of diabetic nephropathy, the main cause of end-stage kidney disease in developed countries. Material and methods: This case–control study was conducted on 23 acromegalic patients and on a control group represented by 21 healthy subjects. The following parameters were determined for all the subjects: serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), nephrin and kidney injury molecule 1 (KIM-1). Results: Patients with acromegaly showed higher levels of UACR and lower levels of eGFR as compared to healthy subjects. No significant correlations were found between clinical or biochemical parameters associated with acromegaly and nephrin or KIM-1. Conclusions: There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients. Full article
13 pages, 1190 KiB  
Systematic Review
Prevalence and Risk Factors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal Artery Angiography: A Systematic Review and Meta-Analysis of 31,689 Patients from 31 Studies
by Konstantin Schwarz, Ida Straume Bah, Maximilian Will, Chun Shing Kwok, Julia Mascherbauer, Marko Kumric, Josko Bozic and Josip A. Borovac
Diseases 2024, 12(9), 208; https://doi.org/10.3390/diseases12090208 - 11 Sep 2024
Viewed by 157
Abstract
Background/Objectives: Renal artery stenosis (RAS) is associated with coronary artery disease (CAD), exacerbation of arterial hypertension, and progression to heart failure, but remains frequently unrecognized in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data [...] Read more.
Background/Objectives: Renal artery stenosis (RAS) is associated with coronary artery disease (CAD), exacerbation of arterial hypertension, and progression to heart failure, but remains frequently unrecognized in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data of patients undergoing CAG due to suspected or stable CAD that received a bilateral renal artery angiography. Results: A total of 31 studies with 31,689 patients were included (mean age 63.2 ± 8.7 years, 20.9% were female). Overall, 13.4% (95%CI 10.5–16.7%) of patients undergoing coronary angiography had significant RAS, with 6.5% (95% CI 4.5–8.9%) and 3.7% (95%CI 2.5–5.2%) having severe and bilateral RAS. The mean weighted proportion of patients with three-vessel coronary disease (3VD) was 25.1 (95%CI 19.6–30.9%) while 4.2% (95%CI 2.6–6.2%) had left main (LM) coronary disease. Patients with RAS compared to those without RAS were significantly older (mean difference, MD 4.2 years (95%CI 3.8–4.6)). The relative risk of RAS was greater for the female sex (risk ratio, 95%CI; RR 1.3, 1.03–1.57), presence of diabetes (RR 1.2, 1.10–1.36), arterial hypertension (RR 1.3, 1.21–1.46), dyslipidemia (RR 1.1, 1.06–1.14), peripheral artery disease (PAD) (RR 2.1, 1.40–3.16), chronic kidney disease (CKD) (RR 2.6, 2.04–3.37), 3VD (RR 1.6, 1.30–1.87), and LM disease (RR 1.8, 1.28–2.47). Smoking had a neutral effect on the risk of RAS occurrence (RR 1.0, 0.94–1.06). Conclusions: RAS is common in patients undergoing coronary angiography. CKD, PAD, older age, and severe CAD were among the strongest predictors for the presence of significant RAS. Full article
(This article belongs to the Section Cardiology)
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8 pages, 1457 KiB  
Case Report
Continued Anticomplement Therapy: A Lifeline for Post-Renal-Transplant Patients with Complement-Mediated Hemolytic Uremic Syndrome
by Natasha Venugopal, Hyma V. Polimera, Jessica Santucci, Erik Washburn and Elizabeth Federici
Therapeutics 2024, 1(1), 34-41; https://doi.org/10.3390/therapeutics1010005 - 11 Sep 2024
Viewed by 211
Abstract
Background: Complement-mediated hemolytic uremic syndrome (CM-HUS), formerly known as atypical HUS, is a rare but potentially fatal thrombotic microangiopathy (TMA) characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and acute kidney injury. It is primarily caused by complement dysregulation. The condition [...] Read more.
Background: Complement-mediated hemolytic uremic syndrome (CM-HUS), formerly known as atypical HUS, is a rare but potentially fatal thrombotic microangiopathy (TMA) characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and acute kidney injury. It is primarily caused by complement dysregulation. The condition can progress to end-stage renal disease (ESRD), often necessitating kidney transplant. In rare instances, it can develop in post-renal-transplant patients. Methods: Here, we present the cases of two patients with ESRD status post kidney transplant who presented with thrombocytopenia, anemia, and acute kidney injury. In both cases, work-up was suggestive of CM-HUS, and stabilization was achieved with eculizumab. Discussion: The pathogenesis of CM-HUS involves dysregulation of the complement system, and complement inhibitors such as eculizumab can be used for initial management and relapse. The relapse rate following eculizumab treatment can range from 20 to 67%. Patients with a history of kidney transplant are more prone to relapse than those with native kidneys. Re-treatment with complement inhibitors has proven effective in managing relapses, and long-term continuation of complement inhibitor medications is recommended to prevent recurrence. Conclusions: CM-HUS is rare, especially in post-transplant patients, and can be potentially fatal. It is crucial for clinicians to recognize and treat this condition promptly. Management often involves complement inhibitors. The risk of relapse is particularly high in patients with a history of kidney transplant, but long-term continuation of these medications can prevent relapse. Full article
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20 pages, 1836 KiB  
Article
Advanced Detection of Abnormal ECG Patterns Using an Optimized LADTree Model with Enhanced Predictive Feature: Potential Application in CKD
by Muhammad Binsawad and Bilal Khan
Algorithms 2024, 17(9), 406; https://doi.org/10.3390/a17090406 - 11 Sep 2024
Viewed by 317
Abstract
Detecting abnormal ECG patterns is a crucial area of study aimed at enhancing diagnostic accuracy and enabling early identification of Chronic Kidney Disease (CKD)-related abnormalities. This study compares a unique strategy for abnormal ECG patterns using the LADTree model to standard machine learning [...] Read more.
Detecting abnormal ECG patterns is a crucial area of study aimed at enhancing diagnostic accuracy and enabling early identification of Chronic Kidney Disease (CKD)-related abnormalities. This study compares a unique strategy for abnormal ECG patterns using the LADTree model to standard machine learning (ML) models. The study design includes data collection from the MIT-BIH Arrhythmia dataset, preprocessing to address missing values, and feature selection using the CfsSubsetEval method using Best First Search, Harmony Search, and Particle Swarm Optimization Search approaches. The performance assessment consists of two scenarios: percentage splitting and K-fold cross-validation, with several evaluation measures such as Kappa statistic (KS), Best First Search, recall, precision-recall curve (PRC) area, receiver operating characteristic (ROC) area, and accuracy. In scenario 1, LADTree outperforms other ML models in terms of mean absolute error (MAE), KS, recall, ROC area, and PRC. Notably, the Naïve Bayes (NB) model has the lowest MAE, but the Support Vector Machine (SVM) performs badly. In scenario 2, NB has the lowest MAE but the highest KS, recall, ROC area, and PRC area, closely followed by LADTree. Overall, the findings indicate that the LADTree model, when optimized for ECG signal data, delivers promising results in detecting abnormal ECG patterns potentially related with CKD. This study advances predictive modeling tools for identifying abnormal ECG patterns, which could enhance early detection and management of CKD, potentially leading to improved patient outcomes and healthcare practices. Full article
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14 pages, 799 KiB  
Review
Roles of the NR2F Family in the Development, Disease, and Cancer of the Lung
by Jiaxin Yang, Wenjing Sun and Guizhong Cui
J. Dev. Biol. 2024, 12(3), 24; https://doi.org/10.3390/jdb12030024 - 10 Sep 2024
Viewed by 320
Abstract
The NR2F family, including NR2F1, NR2F2, and NR2F6, belongs to the nuclear receptor superfamily. NR2F family members function as transcription factors and play essential roles in the development of multiple organs or tissues in mammals, including the central nervous system, veins and arteries, [...] Read more.
The NR2F family, including NR2F1, NR2F2, and NR2F6, belongs to the nuclear receptor superfamily. NR2F family members function as transcription factors and play essential roles in the development of multiple organs or tissues in mammals, including the central nervous system, veins and arteries, kidneys, uterus, and vasculature. In the central nervous system, NR2F1/2 coordinate with each other to regulate the development of specific brain subregions or cell types. In addition, NR2F family members are associated with various cancers, such as prostate cancer, breast cancer, and esophageal cancer. Nonetheless, the roles of the NR2F family in the development and diseases of the lung have not been systematically summarized. In this review, we mainly focus on the lung, including recent findings regarding the roles of the NR2F family in development, physiological function, and cancer. Full article
(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)
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21 pages, 796 KiB  
Review
Maternal Dietary Strategies for Improving Offspring Cardiovascular–Kidney–Metabolic Health: A Scoping Review
by You-Lin Tain and Chien-Ning Hsu
Int. J. Mol. Sci. 2024, 25(18), 9788; https://doi.org/10.3390/ijms25189788 - 10 Sep 2024
Viewed by 262
Abstract
Dietary regulation has been recognized for its profound impact on human health. The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has given rise to cardiovascular–kidney–metabolic (CKM) syndrome, which constitutes a significant global health burden. Maternal dietary nutrients play a [...] Read more.
Dietary regulation has been recognized for its profound impact on human health. The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has given rise to cardiovascular–kidney–metabolic (CKM) syndrome, which constitutes a significant global health burden. Maternal dietary nutrients play a crucial role in fetal development, influencing various programmed processes. This review emphasizes the effects of different types of dietary interventions on each component of CKM syndrome in both preclinical and clinical settings. We also provide an overview of potential maternal dietary strategies, including amino acid supplementation, lipid-associated diets, micronutrients, gut microbiota-targeted diets, and plant polyphenols, aimed at preventing CKM syndrome in offspring. Additionally, we discuss the mechanisms mediated by nutrient-sensing signals that contribute to CKM programming. Altogether, we underscore the interaction between maternal dietary interventions and the risk of CKM syndrome in offspring, emphasizing the need for continued research to facilitate their clinical translation. Full article
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20 pages, 2673 KiB  
Article
Effect of Presence of Uni- or Bilateral Thyroid Adenoma on Recovery of Pituitary–Thyroid Axis and Creatinine Concentration in Radioiodine-Treated Cats
by Anna Paulina Menzel, Joanna Lin, Arne Güssow, Ve Patzelt, Natali Bauer and Katarina Hazuchova
Animals 2024, 14(18), 2627; https://doi.org/10.3390/ani14182627 - 10 Sep 2024
Viewed by 211
Abstract
Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine [...] Read more.
Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine concentration over a period of 6 to 12 months following RAIT. Fifty-one hyperthyroid cats presented for RAIT between April 2021 and April 2022 were prospectively enrolled. Cats with an increased creatinine concentration (creatinine ≥ 140 µmol/L), renal morphology abnormalities, and suspected thyroid carcinoma were excluded. TT4, TSH, and creatinine were determined before and one week and one, three, six, and twelve months following RAIT. The effects of the re-examination timepoint following RAIT and the presence of uni- or bilateral thyroid adenoma based on technetium-99m scintigraphy on TT4, TSH, and creatinine were analysed by mixed effects modelling. Cats with bilateral adenoma had significantly higher TSH concentrations after RAIT compared to those with unilateral adenoma. TT4 concentration significantly decreased one week (p < 0.001) and again one month following RAIT (p < 0.001). TSH and creatinine concentration significantly increased one month post RAIT (both p < 0.001). As indicated by an increase in TSH concentration, the pituitary–thyroid axis needs a minimum of one month post RAIT to recover from hyperthyroidism-induced suppression, but hypothyroidism necessitating levothyroxine supplementation might not be diagnosed before 6 or even 12 months post RAIT. Although creatinine did not increase significantly after one month post RAIT in this cohort, an increased creatinine concentration was detected at later timepoints in individual cats. Full article
(This article belongs to the Section Companion Animals)
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22 pages, 3925 KiB  
Article
Chitosan siRNA Nanoparticles Produce Significant Non-Toxic Functional Gene Silencing in Kidney Cortices
by Mohamad-Gabriel Alameh, Ashkan Tavakoli Naeini, Garima Dwivedi, Frederic Lesage, Michael D. Buschmann and Marc Lavertu
Polymers 2024, 16(17), 2547; https://doi.org/10.3390/polym16172547 - 9 Sep 2024
Viewed by 322
Abstract
Chitosan shows effective nucleic acid delivery. To understand the influence of chitosan’s molecular weight, dose, payload, and hyaluronic acid coating on in vivo toxicity, immune stimulation, biodistribution and efficacy, precisely characterized chitosans were formulated with unmodified or chemically modified siRNA to control for [...] Read more.
Chitosan shows effective nucleic acid delivery. To understand the influence of chitosan’s molecular weight, dose, payload, and hyaluronic acid coating on in vivo toxicity, immune stimulation, biodistribution and efficacy, precisely characterized chitosans were formulated with unmodified or chemically modified siRNA to control for innate immune stimulation. The hemocompatibility, cytokine induction, hematological and serological responses were assessed. Body weight, clinical signs, in vivo biodistribution and functional target knockdown were monitored. Hemolysis was found to be dose- and MW-dependent with the HA coating abrogating hemolysis. Compared to cationic lipid nanoparticles, uncoated and HA-coated chitosan nanoparticles did not induce immune stimulation or hematologic toxicity. Liver and kidney biomarkers remained unchanged with chitosan formulations, while high doses of cationic lipid nanoparticles led to increased transaminase levels and a decrease in body weight. Uncoated and HA-coated nanoparticles accumulated in kidneys with functional knockdown for uncoated chitosan formulations reaching 60%, suggesting potential applications in the treatment of kidney diseases. Full article
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14 pages, 1353 KiB  
Article
C4d Is an Independent Predictor of the Kidney Failure in Primary IgA Nephropathy
by Nikola Zagorec, Ivica Horvatić, Dino Kasumović, Besa Osmani, Slavica Sović, Jagoda Nikić, Matija Horaček, Petar Šenjug, Krešimir Galešić and Danica Galešić Ljubanović
J. Clin. Med. 2024, 13(17), 5338; https://doi.org/10.3390/jcm13175338 - 9 Sep 2024
Viewed by 392
Abstract
Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study [...] Read more.
Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06–32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known. Full article
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16 pages, 1965 KiB  
Article
Proteinuria Assessment and Therapeutic Implementation in Chronic Kidney Disease Patients—A Clinical Audit on KDIGO (“Kidney Disease: Improving Global Outcomes”) Guidelines
by Gabriela Adelakun, Maria Boesing, Munachimso Kizito Mbata, Zahra Pasha, Giorgia Lüthi-Corridori, Fabienne Jaun, Felix Burkhalter and Jörg D. Leuppi
J. Clin. Med. 2024, 13(17), 5335; https://doi.org/10.3390/jcm13175335 - 9 Sep 2024
Viewed by 332
Abstract
Background/Objectives: Chronic kidney disease (CKD) is a major health problem with a rising prevalence due to comorbidities like diabetes and hypertension. The aim of this research was to audit the assessment and therapeutic management of proteinuria in CKD patients at the Cantonal [...] Read more.
Background/Objectives: Chronic kidney disease (CKD) is a major health problem with a rising prevalence due to comorbidities like diabetes and hypertension. The aim of this research was to audit the assessment and therapeutic management of proteinuria in CKD patients at the Cantonal Hospital Baselland (KSBL) in Switzerland and determine associations between patient comorbidities, rehospitalisation, death, and the quality of therapeutic management. Methods: We analysed data from 427 adults with CKD (eGFR < 45 mL/min/1.73 m2) hospitalised on the internal medicine ward in 2022. Results: The mean age was 85 years (range: 79–89), 45.9% were female, and the median eGFR was 32.8 mL/min/1.73 m2 (range: 25–40). Proteinuria assessment was performed in 120 (28.1%) patients (the ProtU group), and a corresponding treatment was prescribed in 59%. The ProtU group had a higher quota of patients with diabetes (44.1% vs. 33%, p = 0.048) and obesity (21.2% vs. 12.5%, p = 0.039) when compared to the group without proteinuria assessment (the Ustix group). Twelve-month survival was not significantly different between the groups (HR: 0.75; 95% CI: 0.488–1.154; p-value = 0.191). However, survival was significantly better in patients who received an antiproteinuric treatment compared to those who did not (HR: 0.30; 95% CI: 0.121–0.0761; p = 0.011). Conclusions: Improvements need to be made in managing CKD at the KSBL in accordance with the guidelines. Full article
(This article belongs to the Section Nephrology & Urology)
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Article
The Quality of Life in Elderly Patients in Comprehensive Conservative Management or Hemodialysis: A Case–Control Study in Analogous Basal Conditions
by Francesca K. Martino, Daniela Campo, Lucia Federica Stefanelli, Alessandra Zattarin, Daria Piccolo, Martina Cacciapuoti, Marco Bogo, Dorella Del Prete, Federico Nalesso and Lorenzo A. Calò
Nutrients 2024, 16(17), 3037; https://doi.org/10.3390/nu16173037 - 9 Sep 2024
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Abstract
Background/Objectives: Comprehensive conservative management (CCM) is a viable treatment option for elderly patients with end-stage kidney disease (ESKD). However, it involves a significant change in dietary habits, such as adopting a low-protein diet. Therefore, it is crucial to understand its impact on the [...] Read more.
Background/Objectives: Comprehensive conservative management (CCM) is a viable treatment option for elderly patients with end-stage kidney disease (ESKD). However, it involves a significant change in dietary habits, such as adopting a low-protein diet. Therefore, it is crucial to understand its impact on the patient’s quality of life (QoL), particularly when compared to hemodialysis (HD). The study aims to evaluate the differences in the QoL between patients undergoing CCM and HD. Methods: The study included 50 patients over 75 with ESKD, with 25 patients in the CCM group and 25 in the HD group. The CCM group followed a personalized low-protein diet, while the HD group did not have protein restrictions. Various parameters were assessed, including demographic data, urine output, blood tests, comorbidity index, Visual Analog Scale (VAS), and hospitalization. The SF-12 questionnaire assessed the QoL, and the Physical Composite Score (PCS) and Mental Composite Score (MCS) were calculated. Results: The study revealed no age and comorbidity index differences between CCM and HD patients. In contrast, CCM patients reported significantly better physical and mental well-being than HD patients. In univariate analysis, CCM (B 0.24, p = 0.001), protein intake (B −0.004, p = 0.008), hospitalization (B −0.18, p = 0.024), urine output (B 0.25, p = 0.001), and VAS (B −0.26, p < 0.001) influenced the PCS. At the same time, only the type of treatment (B = 0.15, p = 0.048), urine output (B 0.18, p = 0.02), and VAS (B −0.14, p = 0.048) influence the MCS. In contrast, in multivariate analysis, only CCM contributed to an improved PCS (B 0.19, p = 0.003) and MCS (B 0.16, p = 0.03), while a higher VAS worsened the PCS (B −0.24, p < 0.001) and MCS (B −0.157, p = 0.0024). Conclusions: In elderly patients with similar basal conditions, health-related QoL perception is better in CCM than in HD patients. Full article
(This article belongs to the Section Geriatric Nutrition)
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