Pub Date : 2024-02-27eCollection Date: 2024-01-01DOI: 10.3389/fneph.2024.1352363
Susanna Lam, Annie Huynh, Tracey Ying, Charbel Sandroussi, David Gracey, Henry C Pleass, Steve Chadban, Jerome M Laurence
Introduction: Wound complications can cause considerable morbidity in kidney transplantation. Closed-incision negative pressure wound therapy (ciNPWT) systems have been efficacious in reducing wound complications across surgical specialties. The aims of this study were to evaluate the use of ciNPWT, Prevena™, in kidney transplant recipients and to determine any association with wound complications.
Material and methods: A single-center, prospective observational cohort study was performed in 2018. A total of 30 consecutive kidney transplant recipients deemed at high risk for wound complications received ciNPWT, and the results were compared to those of a historical cohort of subjects who received conventional dressings. Analysis for recipients with obesity and propensity score matching were performed.
Results: In total, 127 subjects were included in the analysis. Of these, 30 received a ciNPWT dressing and were compared with 97 subjects from a non-study historical control group who had conventional dressing. The overall wound complication rate was 21.3% (27/127). There was no reduction in the rate of wound complications with ciNPWT when compared with conventional dressing [23.3% (7/30) and 20.6% (20/97), respectively, p = 0.75]. In the obese subset (BMI ≥30 kg/m2), there was no significant reduction in wound complications [31.1% (5/16) and 36.8% (7/19), respectively, p = 0.73]. Propensity score matching yielded 26 matched pairs with equivalent rates of wound complications (23.1%, 6/26).
Conclusion: This is the first reported cohort study evaluating the use of ciNPWT in kidney transplantation. While ciNPWT is safe and well tolerated, it is not associated with a statistically significant reduction in wound complications when compared to conventional dressing. The findings from this study will be used to inform future studies associated with ciNPWT in kidney transplantation.
{"title":"Prospective evaluation of a closed-incision negative pressure wound therapy system in kidney transplantation and its association with wound complications.","authors":"Susanna Lam, Annie Huynh, Tracey Ying, Charbel Sandroussi, David Gracey, Henry C Pleass, Steve Chadban, Jerome M Laurence","doi":"10.3389/fneph.2024.1352363","DOIUrl":"10.3389/fneph.2024.1352363","url":null,"abstract":"<p><strong>Introduction: </strong>Wound complications can cause considerable morbidity in kidney transplantation. Closed-incision negative pressure wound therapy (ciNPWT) systems have been efficacious in reducing wound complications across surgical specialties. The aims of this study were to evaluate the use of ciNPWT, Prevena™, in kidney transplant recipients and to determine any association with wound complications.</p><p><strong>Material and methods: </strong>A single-center, prospective observational cohort study was performed in 2018. A total of 30 consecutive kidney transplant recipients deemed at high risk for wound complications received ciNPWT, and the results were compared to those of a historical cohort of subjects who received conventional dressings. Analysis for recipients with obesity and propensity score matching were performed.</p><p><strong>Results: </strong>In total, 127 subjects were included in the analysis. Of these, 30 received a ciNPWT dressing and were compared with 97 subjects from a non-study historical control group who had conventional dressing. The overall wound complication rate was 21.3% (27/127). There was no reduction in the rate of wound complications with ciNPWT when compared with conventional dressing [23.3% (7/30) and 20.6% (20/97), respectively, <i>p</i> = 0.75]. In the obese subset (BMI ≥30 kg/m<sup>2</sup>), there was no significant reduction in wound complications [31.1% (5/16) and 36.8% (7/19), respectively, <i>p</i> = 0.73]. Propensity score matching yielded 26 matched pairs with equivalent rates of wound complications (23.1%, 6/26).</p><p><strong>Conclusion: </strong>This is the first reported cohort study evaluating the use of ciNPWT in kidney transplantation. While ciNPWT is safe and well tolerated, it is not associated with a statistically significant reduction in wound complications when compared to conventional dressing. The findings from this study will be used to inform future studies associated with ciNPWT in kidney transplantation.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1352363"},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-26eCollection Date: 2024-01-01DOI: 10.3389/fneph.2024.1374200
Silvia Maria Orsi, Carlotta Pepino, Lisa Rossoni, Margherita Serafino, Roberta Caorsi, Stefano Volpi, Serena Palmeri, Alessandro Faragli, Francesca Lugani, Carolina Bigatti, Gian Marco Ghiggeri, Enrico Eugenio Verrina, Edoardo La Porta, Andrea Angeletti
[This corrects the article DOI: 10.3389/fneph.2023.1194989.].
[此处更正了文章 DOI：10.3389/fneph.2023.1194989.]。
{"title":"Corrigendum: Case report: Multisystem inflammatory syndrome in children with associated proximal tubular injury.","authors":"Silvia Maria Orsi, Carlotta Pepino, Lisa Rossoni, Margherita Serafino, Roberta Caorsi, Stefano Volpi, Serena Palmeri, Alessandro Faragli, Francesca Lugani, Carolina Bigatti, Gian Marco Ghiggeri, Enrico Eugenio Verrina, Edoardo La Porta, Andrea Angeletti","doi":"10.3389/fneph.2024.1374200","DOIUrl":"https://doi.org/10.3389/fneph.2024.1374200","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fneph.2023.1194989.].</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1374200"},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23eCollection Date: 2024-01-01DOI: 10.3389/fneph.2024.1336863
Saleh Kaysi, Bakhtar Pacha, Maria Mesquita, Frédéric Collart, Joëlle Nortier
Introduction: Systemic congestion and pulmonary congestion (PC) are common in hemodialysis (HD) patients. However, the relationship between these two entities is not quite clear. We study this relationship and attempt to uncover the factors that may affect it considering different inter-dialytic intervals.
Methods: A prospective pilot observational and interventional study including 18 HD patients was conducted. The following were obtained: i) B-line score (BLS) by lung ultrasound (LUS) (reflecting significant pulmonary congestion if BLS > 5), ii) echocardiography, iii) bioelectrical impedance analysis (BIA) (reflecting global volume status), and iv) inferior vena cava (IVC) dynamics (reflecting systemic congestion) before and after the first two consecutive HD sessions of the week, with different inter-dialytic intervals (68 hours and 44 hours). Serum N-terminal pro-brain natriuretic peptide type B (NT-proBNP) levels were obtained before each session. Then, patients were randomized into two groups: the active group, where dry weight was reduced according to BLS + standard of care, and the control group, where dry weight was modified according to standard of care. All the measures were repeated on day 30.
Results: We found no correlation between pulmonary congestion represented by BLS and IVC dimensions and dynamics reflecting systemic congestion, independent of different inter-dialytic intervals. Pulmonary congestion was quite prevalent, as mean pre- and post-dialysis BLSs were quite elevated (16 ± 5.53 and 15.3 ± 6.63, respectively) in the first session compared with the second session (16.3 ± 5.26 and 13.6 ± 5.83, respectively). Systolic (left ventricular ejection fraction) and diastolic cardiac function (e/è ratio) parameters from one side and pulmonary congestion (BLS) from the other were not always correlated. BLS was correlated to e/è ratio before HD (session 1) (R2 = 0.476, p = 0.002) and after HD (session 2) (R2 = 0.193, p = 0.034). Pulmonary congestion reflected by BLS was correlated to the global volume state reflected by BIA only in the second HD session (HD2) (R2 = 0.374, p = 0.007). NT-proBNP levels and BLS were correlated before both sessions (R2 = 0.421, p = 0.004, and R2 = 0.505, p = 0.001, respectively). Systemic congestion was quite prevalent, as mean pre- and post-dialysis IVC dimensions and dynamics were quite elevated in both sessions, with a higher level of systemic congestion in the first HD session (diameter and collapsibility of 2.1 cm and 23%, and 2.01 cm and 19%, respectively) compared with the second session (1.98 cm and 17.5%, and 1.9 cm and 22%, respectively) without reaching statistical significance. IVC dimensions and global volume status measured by BIA were correlated in the second dialysis session (R2
{"title":"Pulmonary congestion and systemic congestion in hemodialysis: dynamics and correlations.","authors":"Saleh Kaysi, Bakhtar Pacha, Maria Mesquita, Frédéric Collart, Joëlle Nortier","doi":"10.3389/fneph.2024.1336863","DOIUrl":"10.3389/fneph.2024.1336863","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic congestion and pulmonary congestion (PC) are common in hemodialysis (HD) patients. However, the relationship between these two entities is not quite clear. We study this relationship and attempt to uncover the factors that may affect it considering different inter-dialytic intervals.</p><p><strong>Methods: </strong>A prospective pilot observational and interventional study including 18 HD patients was conducted. The following were obtained: i) B-line score (BLS) by lung ultrasound (LUS) (reflecting significant pulmonary congestion if BLS > 5), ii) echocardiography, iii) bioelectrical impedance analysis (BIA) (reflecting global volume status), and iv) inferior vena cava (IVC) dynamics (reflecting systemic congestion) before and after the first two consecutive HD sessions of the week, with different inter-dialytic intervals (68 hours and 44 hours). Serum N-terminal pro-brain natriuretic peptide type B (NT-proBNP) levels were obtained before each session. Then, patients were randomized into two groups: the active group, where dry weight was reduced according to BLS + standard of care, and the control group, where dry weight was modified according to standard of care. All the measures were repeated on day 30.</p><p><strong>Results: </strong>We found no correlation between pulmonary congestion represented by BLS and IVC dimensions and dynamics reflecting systemic congestion, independent of different inter-dialytic intervals. Pulmonary congestion was quite prevalent, as mean pre- and post-dialysis BLSs were quite elevated (16 ± 5.53 and 15.3 ± 6.63, respectively) in the first session compared with the second session (16.3 ± 5.26 and 13.6 ± 5.83, respectively). Systolic (left ventricular ejection fraction) and diastolic cardiac function (e/è ratio) parameters from one side and pulmonary congestion (BLS) from the other were not always correlated. BLS was correlated to e/è ratio before HD (session 1) (<i>R</i> <sup>2</sup> = 0.476, <i>p</i> = 0.002) and after HD (session 2) (<i>R</i> <sup>2</sup> = 0.193, <i>p</i> = 0.034). Pulmonary congestion reflected by BLS was correlated to the global volume state reflected by BIA only in the second HD session (HD2) (<i>R</i> <sup>2</sup> = 0.374, <i>p</i> = 0.007). NT-proBNP levels and BLS were correlated before both sessions (<i>R</i> <sup>2</sup> = 0.421, <i>p</i> = 0.004, and <i>R</i> <sup>2</sup> = 0.505, <i>p</i> = 0.001, respectively). Systemic congestion was quite prevalent, as mean pre- and post-dialysis IVC dimensions and dynamics were quite elevated in both sessions, with a higher level of systemic congestion in the first HD session (diameter and collapsibility of 2.1 cm and 23%, and 2.01 cm and 19%, respectively) compared with the second session (1.98 cm and 17.5%, and 1.9 cm and 22%, respectively) without reaching statistical significance. IVC dimensions and global volume status measured by BIA were correlated in the second dialysis session (<i>R</i> <sup>2</sup","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1336863"},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-20eCollection Date: 2024-01-01DOI: 10.3389/fneph.2024.1331510
Sinem Karaterzi, Burkhard Tönshoff, Thurid Ahlenstiel-Grunow, Maral Baghai, Bodo Beck, Anja Büscher, Lisa Eifler, Thomas Giese, Susanne Lezius, Carsten Müller, Jun Oh, Antonia Zapf, Lutz T Weber, Lars Pape
Background: Tacrolimus, a calcineurin inhibitor (CNI), is currently the first-line immunosuppressive agent in kidney transplantation. The therapeutic index of tacrolimus is narrow due to due to the substantial impact of minor variations in drug concentration or exposure on clinical outcomes (i.e., nephrotoxicity), and it has a highly variable intra- and inter-individual bioavailability. Non-adherence to immunosuppressants is associated with rejection after kidney transplantation, which is the main cause of long-term graft loss. Once-daily formulations have been shown to significantly improve adherence compared to twice-daily dosing. Envarsus®, the once-daily prolonged-release formulation of tacrolimus, offers the same therapeutic efficacy as the conventional twice-daily immediate-release tacrolimus formulation (Prograf®) with improved bioavailability, a more consistent pharmacokinetic profile, and a reduced peak to trough, which may reduce CNI-related toxicity. Envarsus® has been approved as an immunosuppressive therapy in adults following kidney or liver transplantation but has not yet been approved in children. The objective of this study is to evaluate the pharmacokinetic profile, efficacy, and tolerability of Envarsus® in children and adolescents aged ≥ 8 and ≤ 18 years to assess its potential role as an additional option for immunosuppressive therapy in children after kidney transplantation.
Methods/design: The study is designed as a randomized, prospective crossover trial. Each patient undergoes two treatment sequences: sequence 1 includes 4 weeks of Envarsus® and sequence 2 includes 4 weeks of Prograf®. Patients are randomized to either group A (sequence 1, followed by sequence 2) or group B (sequence 2, followed by sequence 1). The primary objective is to assess equivalency between total exposure (of tacrolimus area under the curve concentration (AUC0-24)), immediate-release tacrolimus (Prograf®) therapy, and prolonged-release tacrolimus (Envarsus®) using a daily dose conversion factor of 0.7 for prolonged- versus immediate-release tacrolimus. Secondary objectives are the assessment of pharmacodynamics, pharmacogenetics, adherence, gut microbiome analyses, adverse events (including tacrolimus toxicity and biopsy-proven rejections), biopsy-proven rejections, difference in estimated glomerular filtration rate (eGFR), and occurrence of donor-specific antibodies (DSAs).
Discussion: This study will test the hypothesis that once-daily prolonged-release tacrolimus (Envarsus®) is bioequivalent to twice-daily intermediate-release tacrolimus after pediatric kidney transplantation and may reduce toxicity and facilitate medication adherence. This novel concept may optimize immunosuppressive therapy for more stable graft function and increased graft survival by avoiding T-cell mediated and
{"title":"A multi-center interventional study to assess pharmacokinetics, effectiveness, and tolerability of prolonged-release tacrolimus after pediatric kidney transplantation: study protocol for a prospective, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b trial.","authors":"Sinem Karaterzi, Burkhard Tönshoff, Thurid Ahlenstiel-Grunow, Maral Baghai, Bodo Beck, Anja Büscher, Lisa Eifler, Thomas Giese, Susanne Lezius, Carsten Müller, Jun Oh, Antonia Zapf, Lutz T Weber, Lars Pape","doi":"10.3389/fneph.2024.1331510","DOIUrl":"10.3389/fneph.2024.1331510","url":null,"abstract":"<p><strong>Background: </strong>Tacrolimus, a calcineurin inhibitor (CNI), is currently the first-line immunosuppressive agent in kidney transplantation. The therapeutic index of tacrolimus is narrow due to due to the substantial impact of minor variations in drug concentration or exposure on clinical outcomes (i.e., nephrotoxicity), and it has a highly variable intra- and inter-individual bioavailability. Non-adherence to immunosuppressants is associated with rejection after kidney transplantation, which is the main cause of long-term graft loss. Once-daily formulations have been shown to significantly improve adherence compared to twice-daily dosing. Envarsus<sup>®</sup>, the once-daily prolonged-release formulation of tacrolimus, offers the same therapeutic efficacy as the conventional twice-daily immediate-release tacrolimus formulation (Prograf<sup>®</sup>) with improved bioavailability, a more consistent pharmacokinetic profile, and a reduced peak to trough, which may reduce CNI-related toxicity. Envarsus<sup>®</sup> has been approved as an immunosuppressive therapy in adults following kidney or liver transplantation but has not yet been approved in children. The objective of this study is to evaluate the pharmacokinetic profile, efficacy, and tolerability of Envarsus<sup>®</sup> in children and adolescents aged ≥ 8 and ≤ 18 years to assess its potential role as an additional option for immunosuppressive therapy in children after kidney transplantation.</p><p><strong>Methods/design: </strong>The study is designed as a randomized, prospective crossover trial. Each patient undergoes two treatment sequences: sequence 1 includes 4 weeks of Envarsus<sup>®</sup> and sequence 2 includes 4 weeks of Prograf<sup>®</sup>. Patients are randomized to either group A (sequence 1, followed by sequence 2) or group B (sequence 2, followed by sequence 1). The primary objective is to assess equivalency between total exposure (of tacrolimus area under the curve concentration (AUC0-24)), immediate-release tacrolimus (Prograf<sup>®</sup>) therapy, and prolonged-release tacrolimus (Envarsus<sup>®</sup>) using a daily dose conversion factor of 0.7 for prolonged- versus immediate-release tacrolimus. Secondary objectives are the assessment of pharmacodynamics, pharmacogenetics, adherence, gut microbiome analyses, adverse events (including tacrolimus toxicity and biopsy-proven rejections), biopsy-proven rejections, difference in estimated glomerular filtration rate (eGFR), and occurrence of donor-specific antibodies (DSAs).</p><p><strong>Discussion: </strong>This study will test the hypothesis that once-daily prolonged-release tacrolimus (Envarsus<sup>®</sup>) is bioequivalent to twice-daily intermediate-release tacrolimus after pediatric kidney transplantation and may reduce toxicity and facilitate medication adherence. This novel concept may optimize immunosuppressive therapy for more stable graft function and increased graft survival by avoiding T-cell mediated and","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1331510"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01eCollection Date: 2023-01-01DOI: 10.3389/fneph.2023.1346769
Chee Kay Cheung, Jonathan Barratt, Adrian Liew, Hong Zhang, Vladimir Tesar, Richard Lafayette
Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary glomerulonephritis worldwide. Recently, an improved understanding of its underlying pathogenesis and the substantial risk of progression to kidney failure has emerged. The "four-hit hypothesis" of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. Key mediators of the production of Gd-IgA1 and its corresponding autoantibodies are B-cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL), each playing essential roles in the survival and maintenance of B cells and humoral immunity. Elevated serum levels of both BAFF and APRIL are observed in patients with IgAN and correlate with disease severity. This review explores the complex pathogenesis of IgAN, highlighting the pivotal roles of BAFF and APRIL in the interplay between mucosal hyper-responsiveness, B-cell activation, and the consequent overproduction of Gd-IgA1 and its autoantibodies that are key features in this disease. Finally, the potential therapeutic benefits of inhibiting BAFF and APRIL in IgAN, and a summary of recent clinical trial data, will be discussed.
免疫球蛋白 A 肾病（IgAN）以半乳糖缺陷-IgA1（Gd-IgA1）间质沉积为特征，是全球最常见的经活检证实的原发性肾小球肾炎。最近，人们对该病的发病机制及其发展为肾衰竭的巨大风险有了更深入的了解。IgAN 发病机制的 "四击假说 "概述了一个由循环中 Gd-IgA1 水平升高引发自身抗体产生的过程。这导致免疫复合物在肾间质形成和沉积，从而引发炎症和肾损伤。产生 Gd-IgA1 及其相应自身抗体的关键介质是 B 细胞活化因子（BAFF）和 A 增殖诱导配体（APRIL），它们在 B 细胞的存活和维持以及体液免疫中都发挥着重要作用。IgAN患者血清中的BAFF和APRIL水平都会升高，并与疾病的严重程度相关。本综述探讨了 IgAN 复杂的发病机制，强调了 BAFF 和 APRIL 在粘膜高反应性、B 细胞活化以及随之而来的 Gd-IgA1 及其自身抗体过量产生之间的相互作用中的关键作用，而这正是这种疾病的主要特征。最后，将讨论抑制 BAFF 和 APRIL 对 IgAN 的潜在治疗效果，并总结最近的临床试验数据。
{"title":"The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies.","authors":"Chee Kay Cheung, Jonathan Barratt, Adrian Liew, Hong Zhang, Vladimir Tesar, Richard Lafayette","doi":"10.3389/fneph.2023.1346769","DOIUrl":"10.3389/fneph.2023.1346769","url":null,"abstract":"<p><p>Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary glomerulonephritis worldwide. Recently, an improved understanding of its underlying pathogenesis and the substantial risk of progression to kidney failure has emerged. The \"four-hit hypothesis\" of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. Key mediators of the production of Gd-IgA1 and its corresponding autoantibodies are B-cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL), each playing essential roles in the survival and maintenance of B cells and humoral immunity. Elevated serum levels of both BAFF and APRIL are observed in patients with IgAN and correlate with disease severity. This review explores the complex pathogenesis of IgAN, highlighting the pivotal roles of BAFF and APRIL in the interplay between mucosal hyper-responsiveness, B-cell activation, and the consequent overproduction of Gd-IgA1 and its autoantibodies that are key features in this disease. Finally, the potential therapeutic benefits of inhibiting BAFF and APRIL in IgAN, and a summary of recent clinical trial data, will be discussed.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"3 ","pages":"1346769"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.3389/fneph.2023.1237804
Zhiyan Fu, Zhiyu Wang, Karen Clemente, Mohit Jaisinghani, Ken Mei Ting Poon, Anthony Wee Teo Yeo, Gia Lee Ang, A. S. T. Liew, Chee Kong Lim, Marjorie Wai Yin Foo, Wai Leng Chow, Wee An Ta
Chronic kidney disease (CKD) is a major complication of diabetes and a significant disease burden on the healthcare system. The aim of this work was to apply a predictive model to identify high-risk patients in the early stages of CKD as a means to provide early intervention to avert or delay kidney function deterioration.Using the data from the National Diabetes Database in Singapore, we applied a machine-learning algorithm to develop a predictive model for CKD progression in diabetic patients and to deploy the model nationwide.Our model was rigorously validated. It outperformed existing models and clinician predictions. The area under the receiver operating characteristic curve (AUC) of our model is 0.88, with the 95% confidence interval being 0.87 to 0.89. In recognition of its higher and consistent accuracy and clinical usefulness, our CKD model became the first clinical model deployed nationwide in Singapore and has been incorporated into a national program to engage patients in long-term care plans in battling chronic diseases. The risk score generated by the model stratifies patients into three risk levels, which are embedded into the Diabetes Patient Dashboard for clinicians and care managers who can then allocate healthcare resources accordingly.This project provided a successful example of how an artificial intelligence (AI)-based model can be adopted to support clinical decision-making nationwide.
{"title":"Development and deployment of a nationwide predictive model for chronic kidney disease progression in diabetic patients","authors":"Zhiyan Fu, Zhiyu Wang, Karen Clemente, Mohit Jaisinghani, Ken Mei Ting Poon, Anthony Wee Teo Yeo, Gia Lee Ang, A. S. T. Liew, Chee Kong Lim, Marjorie Wai Yin Foo, Wai Leng Chow, Wee An Ta","doi":"10.3389/fneph.2023.1237804","DOIUrl":"https://doi.org/10.3389/fneph.2023.1237804","url":null,"abstract":"Chronic kidney disease (CKD) is a major complication of diabetes and a significant disease burden on the healthcare system. The aim of this work was to apply a predictive model to identify high-risk patients in the early stages of CKD as a means to provide early intervention to avert or delay kidney function deterioration.Using the data from the National Diabetes Database in Singapore, we applied a machine-learning algorithm to develop a predictive model for CKD progression in diabetic patients and to deploy the model nationwide.Our model was rigorously validated. It outperformed existing models and clinician predictions. The area under the receiver operating characteristic curve (AUC) of our model is 0.88, with the 95% confidence interval being 0.87 to 0.89. In recognition of its higher and consistent accuracy and clinical usefulness, our CKD model became the first clinical model deployed nationwide in Singapore and has been incorporated into a national program to engage patients in long-term care plans in battling chronic diseases. The risk score generated by the model stratifies patients into three risk levels, which are embedded into the Diabetes Patient Dashboard for clinicians and care managers who can then allocate healthcare resources accordingly.This project provided a successful example of how an artificial intelligence (AI)-based model can be adopted to support clinical decision-making nationwide.","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"20 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139445654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14DOI: 10.3389/fneph.2023.1282818
F. Jansson Sigfrids, P. Groop
Diabetic kidney disease is distinguished by the presence of albuminuria, hypertension, declining kidney function, and a markedly elevated cardiovascular disease risk. This constellation of clinical features drives the premature mortality associated with type 1 diabetes. The first epidemiological investigations concerning type 1 diabetes-related albuminuria date back to the 1980s. The early studies found that proteinuria – largely equivalent to severe albuminuria – developed in 35 to 45% of individuals with type 1 diabetes, with the diabetes duration-specific incidence rate pattern portraying one or two peaks. Furthermore, moderate albuminuria, the first detectable sign of diabetic kidney disease, was found to nearly inexorably progress to overt kidney disease within a short span of time. Since the early reports, studies presenting more updated incidence rates have appeared, although significant limitations such as study populations that lack broad generalizability, study designs vulnerable to substantive selection bias, and constrained follow-up times have been encountered by many. Nevertheless, the most recent reports estimate that in modern times, moderate – instead of severe – albuminuria develops in one-third of individuals with type 1 diabetes; yet, a considerable part (up to 40% during the first ten years after the initial albuminuria diagnosis) progresses to more advanced stages of the disease over time. An alternative pathway to albuminuria progression is its regression, which affects up to 60% of the individuals, but notably, the relapse rate to a more advanced disease stage is high. Whether albuminuria regression translates into a decline in cardiovascular disease and premature mortality risk is an area of debate, warranting more detailed research in the future. Another unclear but alarming feature is that although the incidence of severe albuminuria has fallen since the 1930s, the decline seems to have reached a plateau after the 1980s. This stagnation may be due to the lack of kidney-protective medicines since the early 1980s, as the recent breakthroughs in type 2 diabetes have not been applicable to type 1 diabetes. Therefore, novel treatment strategies are at high priority within this patient population.
{"title":"Progression and regression of kidney disease in type 1 diabetes","authors":"F. Jansson Sigfrids, P. Groop","doi":"10.3389/fneph.2023.1282818","DOIUrl":"https://doi.org/10.3389/fneph.2023.1282818","url":null,"abstract":"Diabetic kidney disease is distinguished by the presence of albuminuria, hypertension, declining kidney function, and a markedly elevated cardiovascular disease risk. This constellation of clinical features drives the premature mortality associated with type 1 diabetes. The first epidemiological investigations concerning type 1 diabetes-related albuminuria date back to the 1980s. The early studies found that proteinuria – largely equivalent to severe albuminuria – developed in 35 to 45% of individuals with type 1 diabetes, with the diabetes duration-specific incidence rate pattern portraying one or two peaks. Furthermore, moderate albuminuria, the first detectable sign of diabetic kidney disease, was found to nearly inexorably progress to overt kidney disease within a short span of time. Since the early reports, studies presenting more updated incidence rates have appeared, although significant limitations such as study populations that lack broad generalizability, study designs vulnerable to substantive selection bias, and constrained follow-up times have been encountered by many. Nevertheless, the most recent reports estimate that in modern times, moderate – instead of severe – albuminuria develops in one-third of individuals with type 1 diabetes; yet, a considerable part (up to 40% during the first ten years after the initial albuminuria diagnosis) progresses to more advanced stages of the disease over time. An alternative pathway to albuminuria progression is its regression, which affects up to 60% of the individuals, but notably, the relapse rate to a more advanced disease stage is high. Whether albuminuria regression translates into a decline in cardiovascular disease and premature mortality risk is an area of debate, warranting more detailed research in the future. Another unclear but alarming feature is that although the incidence of severe albuminuria has fallen since the 1930s, the decline seems to have reached a plateau after the 1980s. This stagnation may be due to the lack of kidney-protective medicines since the early 1980s, as the recent breakthroughs in type 2 diabetes have not been applicable to type 1 diabetes. Therefore, novel treatment strategies are at high priority within this patient population.","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"2001 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139001884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-09DOI: 10.3389/fneph.2023.1280666
Gift Echefu, Ifeoluwa Stowe, Abdulkareem Lukan, Gaurav Sharma, Indranill Basu-Ray, London Guidry, Jon Schellack, Damodar Kumbala
Central venous stenosis is a significant and frequently encountered problem in managing hemodialysis (HD) patients. Venous hypertension, often accompanied by severe symptoms, undermines the integrity of the hemodialysis access circuit. In central venous stenosis, dialysis through an arteriovenous fistula is usually inefficient, with high recirculation rates and prolonged bleeding after dialysis. Central vein stenosis is a known complication of indwelling intravascular and cardiac devices, such as peripherally inserted central catheters, long-term cuffed hemodialysis catheters, and pacemaker wires. Hence, preventing this challenging condition requires minimization of central venous catheter use. Endovascular interventions are the primary approach for treating central vein stenosis. Percutaneous angioplasty and stent placement may reestablish vascular function in cases of elastic and recurrent lesions. Currently, there is no consensus on the optimal treatment, as existing management approaches have a wide range of patency rates.
{"title":"Central vein stenosis in hemodialysis vascular access: clinical manifestations and contemporary management strategies","authors":"Gift Echefu, Ifeoluwa Stowe, Abdulkareem Lukan, Gaurav Sharma, Indranill Basu-Ray, London Guidry, Jon Schellack, Damodar Kumbala","doi":"10.3389/fneph.2023.1280666","DOIUrl":"https://doi.org/10.3389/fneph.2023.1280666","url":null,"abstract":"Central venous stenosis is a significant and frequently encountered problem in managing hemodialysis (HD) patients. Venous hypertension, often accompanied by severe symptoms, undermines the integrity of the hemodialysis access circuit. In central venous stenosis, dialysis through an arteriovenous fistula is usually inefficient, with high recirculation rates and prolonged bleeding after dialysis. Central vein stenosis is a known complication of indwelling intravascular and cardiac devices, such as peripherally inserted central catheters, long-term cuffed hemodialysis catheters, and pacemaker wires. Hence, preventing this challenging condition requires minimization of central venous catheter use. Endovascular interventions are the primary approach for treating central vein stenosis. Percutaneous angioplasty and stent placement may reestablish vascular function in cases of elastic and recurrent lesions. Currently, there is no consensus on the optimal treatment, as existing management approaches have a wide range of patency rates.","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":" 43","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135290908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-08DOI: 10.3389/fneph.2023.1293907
Hwarang S. Han, Michelle L. Lubetzky
Kidney transplant patients require careful management of immunosuppression to avoid rejection while minimizing the risk of infection and malignancy for the best long-term outcome. The gold standard for monitoring allograft status and immunosuppression adequacy is a kidney biopsy, but this is invasive and costly. Conventional methods of allograft monitoring, such as serum creatinine level, are non-specific. Although they alert physicians to the need to evaluate graft dysfunction, by the time there is a clinical abnormality, allograft damage may have already occurred. The development of novel and non-invasive methods of evaluating allograft status are important to improving graft outcomes. This review summarizes the available conventional and novel methods for monitoring allograft status after kidney transplant. Novel and less invasive methods include gene expression, cell-free DNA, urinary biomarkers, and the use of artificial intelligence. The optimal method to manage patients after kidney transplant is still being investigated. The development of less invasive methods to assess allograft function has the potential to improve patient outcomes and allow for a more personalized approach to immunosuppression management.
{"title":"Immune monitoring of allograft status in kidney transplant recipients","authors":"Hwarang S. Han, Michelle L. Lubetzky","doi":"10.3389/fneph.2023.1293907","DOIUrl":"https://doi.org/10.3389/fneph.2023.1293907","url":null,"abstract":"Kidney transplant patients require careful management of immunosuppression to avoid rejection while minimizing the risk of infection and malignancy for the best long-term outcome. The gold standard for monitoring allograft status and immunosuppression adequacy is a kidney biopsy, but this is invasive and costly. Conventional methods of allograft monitoring, such as serum creatinine level, are non-specific. Although they alert physicians to the need to evaluate graft dysfunction, by the time there is a clinical abnormality, allograft damage may have already occurred. The development of novel and non-invasive methods of evaluating allograft status are important to improving graft outcomes. This review summarizes the available conventional and novel methods for monitoring allograft status after kidney transplant. Novel and less invasive methods include gene expression, cell-free DNA, urinary biomarkers, and the use of artificial intelligence. The optimal method to manage patients after kidney transplant is still being investigated. The development of less invasive methods to assess allograft function has the potential to improve patient outcomes and allow for a more personalized approach to immunosuppression management.","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135430111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-03DOI: 10.3389/fneph.2023.1284814
Rodolfo Moreno-Alvarado, Guillermo Navarro-Blackaller, Werner De Leon-Pérez, David Armas-Eguizabal, Jonathan Chávez-Iñiguez
Introduction Acute postinfectious glomerulonephritis (APIGN) is an immunological glomerular disease that is an important health issue in developing countries. The incidence remains high in developing countries with a male-to-female ratio of 2:1 and age predominantly above 50 years. In this case study, we present a patient with a history of Staphylococcus epidermidis infection, a past medical history of diabetes mellitus, and histopathological findings of APIGN with Immunoglobulin A (IgA) deposition. Methods A 58-year-old male presented to the emergency room with a 6-day history of severe low back pain. Three days later, the patient developed fever, chills, abdominal pain in the upper quadrant and a subsequent lower limb cellulitis. Various immunological tests, imaging studies, and kidney biopsy were performed to arrive at a diagnosis. Results Following the diagnosis and treatment of Cholangitis and Staphylococcus epidermidis , further investigation led to a diagnosis of IgA-dominant APIGN. IgA-dominant APIGN was treated with antibiotics, renin-angiotensin-aldosterone system inhibitors and steroids, and the patient was discharged from the hospital. Conclusion In developing countries, APIGN is a relatively common presentation of kidney damage due to acute kidney injury and nephritic syndrome. IgA-dominant APIGN is a rare but increasingly recognized morphological variant in which IgA is the sole or dominant immunoglobulin. This unique presentation and multidisciplinary approach for diagnosing and treating IgA-dominant APIGN need to be considered and understood by healthcare professionals to better help these patients. Further investigation is needed to understand the best treatment of this IgA-dominant APIGN presentation and its prognosis.
{"title":"IgA-dominant postinfectious glomerulonephritis: a case report","authors":"Rodolfo Moreno-Alvarado, Guillermo Navarro-Blackaller, Werner De Leon-Pérez, David Armas-Eguizabal, Jonathan Chávez-Iñiguez","doi":"10.3389/fneph.2023.1284814","DOIUrl":"https://doi.org/10.3389/fneph.2023.1284814","url":null,"abstract":"Introduction Acute postinfectious glomerulonephritis (APIGN) is an immunological glomerular disease that is an important health issue in developing countries. The incidence remains high in developing countries with a male-to-female ratio of 2:1 and age predominantly above 50 years. In this case study, we present a patient with a history of Staphylococcus epidermidis infection, a past medical history of diabetes mellitus, and histopathological findings of APIGN with Immunoglobulin A (IgA) deposition. Methods A 58-year-old male presented to the emergency room with a 6-day history of severe low back pain. Three days later, the patient developed fever, chills, abdominal pain in the upper quadrant and a subsequent lower limb cellulitis. Various immunological tests, imaging studies, and kidney biopsy were performed to arrive at a diagnosis. Results Following the diagnosis and treatment of Cholangitis and Staphylococcus epidermidis , further investigation led to a diagnosis of IgA-dominant APIGN. IgA-dominant APIGN was treated with antibiotics, renin-angiotensin-aldosterone system inhibitors and steroids, and the patient was discharged from the hospital. Conclusion In developing countries, APIGN is a relatively common presentation of kidney damage due to acute kidney injury and nephritic syndrome. IgA-dominant APIGN is a rare but increasingly recognized morphological variant in which IgA is the sole or dominant immunoglobulin. This unique presentation and multidisciplinary approach for diagnosing and treating IgA-dominant APIGN need to be considered and understood by healthcare professionals to better help these patients. Further investigation is needed to understand the best treatment of this IgA-dominant APIGN presentation and its prognosis.","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"23 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135819782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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