{"title":"Blood Pressure Beyond the Dialysis Chair.","authors":"Daniel Gallego","doi":"10.2215/cjn.0000000957","DOIUrl":"https://doi.org/10.2215/cjn.0000000957","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Boosting CONFIDENCE in Combination Therapy for Diabetic Kidney Disease in Asia.","authors":"Mengyao Tang,Sahir Kalim","doi":"10.2215/cjn.0000000959","DOIUrl":"https://doi.org/10.2215/cjn.0000000959","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"\"See You in the Morning?\"-Can Hypothermic Machine Perfusion Allow Longer Ischemic Times without Compromising Transplant Outcomes?","authors":"Dylan R Barnett,Michael G Collins","doi":"10.2215/cjn.0000000960","DOIUrl":"https://doi.org/10.2215/cjn.0000000960","url":null,"abstract":"","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"69 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and is characterized by the progressive growth of multiple kidney cysts, leading to kidney failure in most patients. The management of ADPKD, which up to a decade ago was limited to supportive measures to preserve kidney function and prevent complications, has evolved with the regulatory approval of disease-modifying agents. This review provided an overview of the current status and future perspectives of treatment for ADPKD. At present, the only drugs approved to slow disease progression are the vasopressin V2-receptor antagonist tolvaptan and, in Italy, the somatostatin analogue octreotide long-acting release for the subset of patients with stage 4 chronic kidney disease. However, various therapeutic strategies are under clinical investigation. These include not only repurposed pharmacological agents, namely sodium-glucose cotransporter-2 inhibitors, metformin, and glucagon-like peptide-1 receptor agonists, but also innovative therapies, as it is the case for a monoclonal antibody against pregnancy-associated plasma protein-A, microRNA-17 inhibitors, and the polycystin-1 correcting agent VX-407. Dietary interventions, such as caloric restriction and ketogenic diets, are being tested in clinical trials as well, and could complement pharmacotherapy to slow disease progression. Moreover, the rapid advancements in the field of gene therapy for ADPKD suggest that this approach, though as yet only explored at experimental level, could be translated into clinical practice in future to correct the underlying genetic defect, and potentially reverse disease pathogenesis, thereby improving patient outcomes.
{"title":"THE NEED FOR NOVEL THERAPEUTIC DIRECTIONS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENT CARE.","authors":"Monica Cortinovis,Norberto Perico,Giuseppe Remuzzi","doi":"10.2215/cjn.0000000975","DOIUrl":"https://doi.org/10.2215/cjn.0000000975","url":null,"abstract":"Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and is characterized by the progressive growth of multiple kidney cysts, leading to kidney failure in most patients. The management of ADPKD, which up to a decade ago was limited to supportive measures to preserve kidney function and prevent complications, has evolved with the regulatory approval of disease-modifying agents. This review provided an overview of the current status and future perspectives of treatment for ADPKD. At present, the only drugs approved to slow disease progression are the vasopressin V2-receptor antagonist tolvaptan and, in Italy, the somatostatin analogue octreotide long-acting release for the subset of patients with stage 4 chronic kidney disease. However, various therapeutic strategies are under clinical investigation. These include not only repurposed pharmacological agents, namely sodium-glucose cotransporter-2 inhibitors, metformin, and glucagon-like peptide-1 receptor agonists, but also innovative therapies, as it is the case for a monoclonal antibody against pregnancy-associated plasma protein-A, microRNA-17 inhibitors, and the polycystin-1 correcting agent VX-407. Dietary interventions, such as caloric restriction and ketogenic diets, are being tested in clinical trials as well, and could complement pharmacotherapy to slow disease progression. Moreover, the rapid advancements in the field of gene therapy for ADPKD suggest that this approach, though as yet only explored at experimental level, could be translated into clinical practice in future to correct the underlying genetic defect, and potentially reverse disease pathogenesis, thereby improving patient outcomes.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey Perl,Isaac Teitelbaum,Bradley A Warady,Alicia Neu,Suzanne Watnick,Dinesh Chatoth,Joel Glickman,Kristina Bryant,Margaret Bushey,Meghan Finn,Allison Taylor,Cathie Wahlin,Laurie Wolf,Kerry A Leigh,Joseph Kessler,Edward Gould
For some patients, peritoneal dialysis (PD) has several advantages over center-based hemodialysis (HD). PD-related infections such as peritonitis, and PD catheter exit-site and tunnel infections are a significant source of morbidity. Peritonitis leads to increased mortality, and it is the leading cause of transfer off PD. Infection prevention practices may vary widely across dialysis centers, resulting in significant differences in infection rates. To address these issues and improve patient outcomes, the American Society of Nephrology (ASN) facilitated the development of core interventions aimed at reducing PD-related infections across United States (U.S.)dialysis facilities. The core interventions focus on six key strategies: (1) regular surveillance and feedback on infection rates, (2) standardized staff training and competency assessments, (3) standardized patient and care partner/giver education, (4) routine infection prevention assessments, (5) antimicrobial prophylaxis for PD catheter exit sites, and (6) prophylactic antimicrobials for certain procedures and events. These strategies, based on evidence and international guidelines, emphasize consistency in implementation and monitoring at the facility level. The workgroup followed an iterative process, incorporating expert review and feedback to inform and refine these interventions. Effective implementation requires coordinated efforts among dialysis teams, patients, and support networks, with ongoing evaluation through surveillance and quality improvement initiatives. While the interventions are grounded in current evidence, further research is necessary to refine practices and address emerging challenges. The goal is to reduce infection risks, improve quality of life for patients on PD, and support national efforts to expand home dialysis use.
{"title":"Core Interventions for the Prevention of Peritoneal Dialysis Related Infections.","authors":"Jeffrey Perl,Isaac Teitelbaum,Bradley A Warady,Alicia Neu,Suzanne Watnick,Dinesh Chatoth,Joel Glickman,Kristina Bryant,Margaret Bushey,Meghan Finn,Allison Taylor,Cathie Wahlin,Laurie Wolf,Kerry A Leigh,Joseph Kessler,Edward Gould","doi":"10.2215/cjn.0000000976","DOIUrl":"https://doi.org/10.2215/cjn.0000000976","url":null,"abstract":"For some patients, peritoneal dialysis (PD) has several advantages over center-based hemodialysis (HD). PD-related infections such as peritonitis, and PD catheter exit-site and tunnel infections are a significant source of morbidity. Peritonitis leads to increased mortality, and it is the leading cause of transfer off PD. Infection prevention practices may vary widely across dialysis centers, resulting in significant differences in infection rates. To address these issues and improve patient outcomes, the American Society of Nephrology (ASN) facilitated the development of core interventions aimed at reducing PD-related infections across United States (U.S.)dialysis facilities. The core interventions focus on six key strategies: (1) regular surveillance and feedback on infection rates, (2) standardized staff training and competency assessments, (3) standardized patient and care partner/giver education, (4) routine infection prevention assessments, (5) antimicrobial prophylaxis for PD catheter exit sites, and (6) prophylactic antimicrobials for certain procedures and events. These strategies, based on evidence and international guidelines, emphasize consistency in implementation and monitoring at the facility level. The workgroup followed an iterative process, incorporating expert review and feedback to inform and refine these interventions. Effective implementation requires coordinated efforts among dialysis teams, patients, and support networks, with ongoing evaluation through surveillance and quality improvement initiatives. While the interventions are grounded in current evidence, further research is necessary to refine practices and address emerging challenges. The goal is to reduce infection risks, improve quality of life for patients on PD, and support national efforts to expand home dialysis use.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"28 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheol Ho Park,Yujoon Kim,Chaeeun Kim,Chaehyung Kim,Sowon Kim,Kangwon Lee,Tae-Hyun Yoo
BACKGROUNDHyperkalemia is a common electrolyte imbalance leading to an increased risk of serious cardiac dysrhythmias and mortality in patients undergoing hemodialysis. A convenient point-of-care testing (POCT) of potassium levels is considered to improve patient outcomes. However, POCT for potassium level using capillary blood with satisfactory performance is not available.METHODSWe tested the performance of disposable test strips for potassium level using various concentrations of potassium solutions with or without interfering electrolytes in an experimental setting. Subsequently, we examined the agreement between potassium levels measured by disposable test strips and those measured by central laboratory equipment using various types of blood samples, including capillary blood obtained by finger prick, in 40 patients undergoing maintenance hemodialysis. In the analysis, Passing-Bablok regression and Bland-Altman analysis were employed.RESULTSPotassium concentrations measured by disposable test strips showed a high degree of agreement with potassium levels achieved using inductively coupled plasma atomic emission spectroscopy. The coefficient of variations for disposable test strips were less than 5% across potassium concentrations ranging from 2 to 9 mM. Furthermore, potassium levels measured by disposable strips from capillary blood demonstrated a high degree of agreement with potassium levels obtained by central laboratory equipment using serum, showing the slope achieved from Passing-Bablok regression was 1.04 (95% CI, 0.97 to 1.12). Additional analysis with various blood samples also showed similar results.CONCLUSIONPOCT for potassium level using the disposable test strip could be employed for self-monitoring of blood potassium levels in clinical practice.
{"title":"Clinical Evaluation of a Disposable Test Strip for Potassium Level Measurement in Patients Treated with Maintenance Hemodialysis.","authors":"Cheol Ho Park,Yujoon Kim,Chaeeun Kim,Chaehyung Kim,Sowon Kim,Kangwon Lee,Tae-Hyun Yoo","doi":"10.2215/cjn.0000000934","DOIUrl":"https://doi.org/10.2215/cjn.0000000934","url":null,"abstract":"BACKGROUNDHyperkalemia is a common electrolyte imbalance leading to an increased risk of serious cardiac dysrhythmias and mortality in patients undergoing hemodialysis. A convenient point-of-care testing (POCT) of potassium levels is considered to improve patient outcomes. However, POCT for potassium level using capillary blood with satisfactory performance is not available.METHODSWe tested the performance of disposable test strips for potassium level using various concentrations of potassium solutions with or without interfering electrolytes in an experimental setting. Subsequently, we examined the agreement between potassium levels measured by disposable test strips and those measured by central laboratory equipment using various types of blood samples, including capillary blood obtained by finger prick, in 40 patients undergoing maintenance hemodialysis. In the analysis, Passing-Bablok regression and Bland-Altman analysis were employed.RESULTSPotassium concentrations measured by disposable test strips showed a high degree of agreement with potassium levels achieved using inductively coupled plasma atomic emission spectroscopy. The coefficient of variations for disposable test strips were less than 5% across potassium concentrations ranging from 2 to 9 mM. Furthermore, potassium levels measured by disposable strips from capillary blood demonstrated a high degree of agreement with potassium levels obtained by central laboratory equipment using serum, showing the slope achieved from Passing-Bablok regression was 1.04 (95% CI, 0.97 to 1.12). Additional analysis with various blood samples also showed similar results.CONCLUSIONPOCT for potassium level using the disposable test strip could be employed for self-monitoring of blood potassium levels in clinical practice.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"5 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conflicts severely disrupt care for patients with kidney failure, often limiting access to dialysis. In these challenging settings, conservative kidney management (CKM) emerges as a compassionate alternative focused on quality of life and symptom relief. This study explores how conflict conditions shape nephrologists' perceptions and implementation of CKM across the Middle East and North Africa (MENA) region. A web-based survey was distributed across 17 Arabic-speaking MENA countries over three months in 2022. Responses were divided into two groups according to the country's conflict status. Of the 334 nephrologist respondents, 66 were practicing in conflict zones and 268 in non-conflict zones. Conflict-zone respondents were more likely to work part-time and less likely to be female. Dialysis in conflict zones was more likely funded by charitable sources (OR 4.22, 95% CI 1.36-13.07). Compared to non-conflict zones, nephrologists in conflict areas reported significantly less access to palliative care (OR 3.36, 95% CI 1.3-8.68) and cited lack of CKM training and limited access to CKM programs as barriers to its implementation (OR 2.59, 95% CI 1.24-5.38 and OR 3.42, 95% CI 1.59-7.35, respectively). While overall awareness of CKM was similar, those in conflict zones expressed greater moral and religious discomfort with withholding dialysis. These findings underscore important ethical, operational, and access-related disparities in CKM delivery in conflict zones in the MENA region. Addressing these gaps through supportive ethical policies focusing on procedural and distributive justice, increased nephrologists' awareness and training, and enhanced efforts to strengthen palliative care services are essential tools for establishing CKM as a viable and ethical approach for patients in conflict-affected regions.
冲突严重扰乱了对肾衰竭患者的护理，往往限制了透析的获得。在这些具有挑战性的环境中，保守肾脏管理（CKM）作为一种关注生活质量和症状缓解的富有同情心的替代方案出现。本研究探讨了冲突条件如何影响肾病学家对中东和北非（MENA）地区CKM的看法和实施。2022年，一项基于网络的调查在17个讲阿拉伯语的中东和北非国家进行了为期三个月的分发。根据该国的冲突状况，回答被分为两组。在334名接受调查的肾病专家中，66名在冲突地区执业，268名在非冲突地区执业。冲突地区的受访者更有可能从事兼职工作，女性的可能性更小。冲突地区的透析更有可能由慈善机构资助（OR 4.22, 95% CI 1.36-13.07）。与非冲突地区相比，冲突地区的肾病学家获得姑息治疗的机会明显更少（OR 3.36, 95% CI 1.3-8.68），并将CKM培训的缺乏和CKM项目的有限获取列为实施的障碍（OR 2.59, 95% CI 1.24-5.38和OR 3.42, 95% CI 1.59-7.35）。虽然对CKM的总体认识是相似的，但冲突地区的人对停止透析表现出更大的道德和宗教不适。这些研究结果强调了中东和北非地区冲突地区在提供CKM方面存在的重要的道德、操作和可及性差异。通过注重程序和分配公正的支持性伦理政策、提高肾病学家的意识和培训以及加强姑息治疗服务来解决这些差距，是为受冲突影响地区的患者建立CKM作为一种可行和合乎道德的方法的重要工具。
{"title":"Conservative Kidney Management in the Middle East and North Africa: A Comparative Study of Conflict and Non-Conflict Settings.","authors":"Akram Al-Makki,David Gunderman,Valerie Luyckx,Taha Hatab,Imed Helal,Mayssaa Hoteit,Rana Yamout,Ala Ali,Abdulhafid Shebani,Najib AbuOsba,Mohamed H Sayegh,Krishna Allam,Sahar Koubar","doi":"10.2215/cjn.0000000900","DOIUrl":"https://doi.org/10.2215/cjn.0000000900","url":null,"abstract":"Conflicts severely disrupt care for patients with kidney failure, often limiting access to dialysis. In these challenging settings, conservative kidney management (CKM) emerges as a compassionate alternative focused on quality of life and symptom relief. This study explores how conflict conditions shape nephrologists' perceptions and implementation of CKM across the Middle East and North Africa (MENA) region. A web-based survey was distributed across 17 Arabic-speaking MENA countries over three months in 2022. Responses were divided into two groups according to the country's conflict status. Of the 334 nephrologist respondents, 66 were practicing in conflict zones and 268 in non-conflict zones. Conflict-zone respondents were more likely to work part-time and less likely to be female. Dialysis in conflict zones was more likely funded by charitable sources (OR 4.22, 95% CI 1.36-13.07). Compared to non-conflict zones, nephrologists in conflict areas reported significantly less access to palliative care (OR 3.36, 95% CI 1.3-8.68) and cited lack of CKM training and limited access to CKM programs as barriers to its implementation (OR 2.59, 95% CI 1.24-5.38 and OR 3.42, 95% CI 1.59-7.35, respectively). While overall awareness of CKM was similar, those in conflict zones expressed greater moral and religious discomfort with withholding dialysis. These findings underscore important ethical, operational, and access-related disparities in CKM delivery in conflict zones in the MENA region. Addressing these gaps through supportive ethical policies focusing on procedural and distributive justice, increased nephrologists' awareness and training, and enhanced efforts to strengthen palliative care services are essential tools for establishing CKM as a viable and ethical approach for patients in conflict-affected regions.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"36 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDNephronophthisis (NPH) is an autosomal recessive tubulointerstitial kidney disease and a leading genetic cause of chronic kidney failure (KF) in children and young adults. As a ciliopathy, NPH is caused by biallelic variants in genes encoding proteins involved in the structure and function of primary cilia. The broad clinical spectrum of NPH results in a clinically and genetically heterogeneous disease, posing diagnostic challenges and leaving approximately 30% of cases unresolved with current gene panels.METHODSAfter targeted gene panel for ciliopathy-associated genes failed to identify diagnostic variants, exome sequencing (ES) was conducted on 42 unrelated index patients with a clinical diagnosis of NPH, defined as cystic nephropathy progressing to KF within the first two decades of life, or by unspecific chronic kidney disease (CKD) accompanied by extrarenal features indicative of a ciliopathy.RESULTSPathogenic or likely pathogenic variants were identified in 11 out of the 42 patients (26%). Variants were detected in known nephropathy genes (LAMB2, COQ8B, COL4A3, MUC1) and a multisystem disease gene with secondary kidney involvement (AGXT). Additionally, ES elucidated deleterious variants explaining extrarenal phenotypes without corresponding kidney disease in six patients (APTX, TUBB3, DHX38, IQCE, CRX, RPGR). Variants of unknown significance (VUS) were identified in three patients, while heterozygous variants in genes associated with recessive disease were observed in three others. A potential candidate gene for syndromic tubulointerstitial nephropathy, SSBP1, was also identified, suggesting a novel pathway involving mitochondrial dysfunction.CONCLUSIONSES enabled the identification of pathogenic variants in known genes associated with kidney diseases, non-kidney conditions, and multisystem disorders with secondary kidney involvement, thereby improving diagnosis accuracy, even in incomplete or atypical cases, and guiding specific diagnostic and therapeutic approaches. The identification of SSBP1 in association with tubulointerstitial nephropathy may provide new insights into the pathogenesis of ciliopathies.
{"title":"Exome Sequencing in a Large Cohort with Ciliopathy-Related Kidney Disease.","authors":"Friederike Petzold,Cécile Jeanpierre,Xiaoyi Chen,Vincent Morinière,Alexandre Benmerah,Guillaume Dorval,Hassan Saei,Laurence Heidet,Corinne Antignac,Sophie Saunier, ","doi":"10.2215/cjn.0000000905","DOIUrl":"https://doi.org/10.2215/cjn.0000000905","url":null,"abstract":"BACKGROUNDNephronophthisis (NPH) is an autosomal recessive tubulointerstitial kidney disease and a leading genetic cause of chronic kidney failure (KF) in children and young adults. As a ciliopathy, NPH is caused by biallelic variants in genes encoding proteins involved in the structure and function of primary cilia. The broad clinical spectrum of NPH results in a clinically and genetically heterogeneous disease, posing diagnostic challenges and leaving approximately 30% of cases unresolved with current gene panels.METHODSAfter targeted gene panel for ciliopathy-associated genes failed to identify diagnostic variants, exome sequencing (ES) was conducted on 42 unrelated index patients with a clinical diagnosis of NPH, defined as cystic nephropathy progressing to KF within the first two decades of life, or by unspecific chronic kidney disease (CKD) accompanied by extrarenal features indicative of a ciliopathy.RESULTSPathogenic or likely pathogenic variants were identified in 11 out of the 42 patients (26%). Variants were detected in known nephropathy genes (LAMB2, COQ8B, COL4A3, MUC1) and a multisystem disease gene with secondary kidney involvement (AGXT). Additionally, ES elucidated deleterious variants explaining extrarenal phenotypes without corresponding kidney disease in six patients (APTX, TUBB3, DHX38, IQCE, CRX, RPGR). Variants of unknown significance (VUS) were identified in three patients, while heterozygous variants in genes associated with recessive disease were observed in three others. A potential candidate gene for syndromic tubulointerstitial nephropathy, SSBP1, was also identified, suggesting a novel pathway involving mitochondrial dysfunction.CONCLUSIONSES enabled the identification of pathogenic variants in known genes associated with kidney diseases, non-kidney conditions, and multisystem disorders with secondary kidney involvement, thereby improving diagnosis accuracy, even in incomplete or atypical cases, and guiding specific diagnostic and therapeutic approaches. The identification of SSBP1 in association with tubulointerstitial nephropathy may provide new insights into the pathogenesis of ciliopathies.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yaacov Frishberg,Jeffrey M Saland,John C Lieske,Weiming Du,Martin Coenen,Julien Hogan,Anne-Laure Sellier-Leclerc,Jaap W Groothoff,Cristin Kaspar,John M Gansner,Sally-Anne Hulton,
BACKGROUNDPrimary hyperoxaluria type 1 (PH1) is characterized by hepatic oxalate overproduction, kidney stones, and progressive kidney disease. Lumasiran is the first approved treatment for PH1.METHODSILLUMINATE-A (NCT03681184) was a 60-month pivotal, phase 3, multinational clinical trial of lumasiran which consisted of a six-month double-blind, placebo-controlled period (6M DB) followed by a treatment extension period of up to 54 months in which all patients received lumasiran. Eligible patients were aged ≥6 years with genetically confirmed PH1, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2, and mean 24-hour urinary oxalate (UOx) excretion ≥0.70 mmol/24h/1.73m2.RESULTSOf 39 patients enrolled, 24 out of 26 randomized to lumasiran in the 6M DB (lumasiran/lumasiran group) and 13 out of 13 randomized to placebo in the 6M DB (placebo/lumasiran group) completed the study. Sustained reductions in 24-hour UOx were observed in both treatment groups. At Month 60 relative to study baseline, mean (standard error of the mean [SEM]) 24-hour UOx percentage reductions were 54% (6%) and 54% (8%) in the lumasiran/lumasiran and placebo/lumasiran groups, respectively, and mean (SEM) plasma oxalate concentrations had decreased by 35% (5%) and 38% (7%). Estimated glomerular filtration rate remained stable through the end of the study in both treatment groups. Kidney stone event rates during the study were 0.47 (95% confidence interval [CI], 0.36, 0.62) and 0.54 (0.37, 0.78) per patient-year in the lumasiran/lumasiran group and placebo/lumasiran group, respectively. Medullary nephrocalcinosis grade improved at the end of the study in 21 out of 28 (75%) patients with nephrocalcinosis at baseline and an end of study assessment. The safety profile of lumasiran was acceptable. Injection site reactions were the most common adverse events during lumasiran treatment. Most adverse events were mild or moderate in severity.CONCLUSIONSLumasiran treatment for up to 60 months in ILLUMINATE-A was associated with sustained reductions in UOx excretion and plasma oxalate concentration, and encouraging clinical outcomes including stable eGFR in a population that would be expected to show eGFR decline, reduced kidney stone event rates, improved medullary nephrocalcinosis, and indications of improved quality of life.
{"title":"Final Results of the ILLUMINATE-A Phase 3 Clinical Trial of Lumasiran for Primary Hyperoxaluria 1.","authors":"Yaacov Frishberg,Jeffrey M Saland,John C Lieske,Weiming Du,Martin Coenen,Julien Hogan,Anne-Laure Sellier-Leclerc,Jaap W Groothoff,Cristin Kaspar,John M Gansner,Sally-Anne Hulton, ","doi":"10.2215/cjn.0000000916","DOIUrl":"https://doi.org/10.2215/cjn.0000000916","url":null,"abstract":"BACKGROUNDPrimary hyperoxaluria type 1 (PH1) is characterized by hepatic oxalate overproduction, kidney stones, and progressive kidney disease. Lumasiran is the first approved treatment for PH1.METHODSILLUMINATE-A (NCT03681184) was a 60-month pivotal, phase 3, multinational clinical trial of lumasiran which consisted of a six-month double-blind, placebo-controlled period (6M DB) followed by a treatment extension period of up to 54 months in which all patients received lumasiran. Eligible patients were aged ≥6 years with genetically confirmed PH1, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2, and mean 24-hour urinary oxalate (UOx) excretion ≥0.70 mmol/24h/1.73m2.RESULTSOf 39 patients enrolled, 24 out of 26 randomized to lumasiran in the 6M DB (lumasiran/lumasiran group) and 13 out of 13 randomized to placebo in the 6M DB (placebo/lumasiran group) completed the study. Sustained reductions in 24-hour UOx were observed in both treatment groups. At Month 60 relative to study baseline, mean (standard error of the mean [SEM]) 24-hour UOx percentage reductions were 54% (6%) and 54% (8%) in the lumasiran/lumasiran and placebo/lumasiran groups, respectively, and mean (SEM) plasma oxalate concentrations had decreased by 35% (5%) and 38% (7%). Estimated glomerular filtration rate remained stable through the end of the study in both treatment groups. Kidney stone event rates during the study were 0.47 (95% confidence interval [CI], 0.36, 0.62) and 0.54 (0.37, 0.78) per patient-year in the lumasiran/lumasiran group and placebo/lumasiran group, respectively. Medullary nephrocalcinosis grade improved at the end of the study in 21 out of 28 (75%) patients with nephrocalcinosis at baseline and an end of study assessment. The safety profile of lumasiran was acceptable. Injection site reactions were the most common adverse events during lumasiran treatment. Most adverse events were mild or moderate in severity.CONCLUSIONSLumasiran treatment for up to 60 months in ILLUMINATE-A was associated with sustained reductions in UOx excretion and plasma oxalate concentration, and encouraging clinical outcomes including stable eGFR in a population that would be expected to show eGFR decline, reduced kidney stone event rates, improved medullary nephrocalcinosis, and indications of improved quality of life.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"159 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Bragg-Gresham,Fang Xu,Yun Han,Ana Laura Licon,Jenna Kiryakos,Michael Heung,Hal Morgenstern,William Weitzel,Tiffany Veinot,Brenda Gillespie,Zubin J Modi,William Herman,Tracey Pérez Koehlmoos,Robert Nee,James D Oliver,Sola Han,Meda E Pavkov,Rajiv Saran
Kidney diseases are an important public health problem, rising in global significance. In place for nearly two decades, the Centers for Disease Control and Prevention's Kidney Disease Surveillance System (KDSS) is the first comprehensive surveillance system developed in the United States, focused exclusively on tracking kidney disease prior to end-stage kidney disease. The KDSS incorporates key data and trends from multiple, large national-level survey data sources (National Health and Nutrition Examination Survey), electronic medical record data (Military and Veterans Affairs Health Systems), health care claims (Medicare, Optum), and social determinants of health (American Community Survey). The prevalence of chronic kidney disease (CKD) among civilian US adults remains steady between 13%─14%. Prevalence is higher among older, female, non-Hispanic Black adults, and those with diabetes or hypertension. Among US veterans, the incidence of CKD and rates of diagnosis of acute kidney injury (AKI) increased from 2008 to 2022 (Incidence: 62.8 to 71.5/1,000 person-years, AKI: 84.9 to 241.7 cases/1,000 person-years. Awareness of the disease nationwide among persons with CKD has historically been low (<10%), but starting in 2013, has increased to approximately 25%. Persons with CKD self-report more problems with sleep, and those aged 65 and older self-report a higher prevalence of functional limitations. Improvements in quality-of-care measures, including medication prescription and increases in both serum creatinine and albuminuria testing were observed. Increased self-reported physical activity was observed among persons with CKD. Food insecurity increased among persons with CKD, with the highest prevalence in young, female, non-Hispanic Black, and Hispanic adults. While population-level prevalence of CKD remains stable, higher AKI and CKD rates are being observed in health systems settings. Robust surveillance is key to raising awareness of kidney disease, its risk factors, care quality, and outcomes. Surveillance findings may inform policy and evidence-based practices that reduce premature morbidity and mortality, improve quality of life, and reduce cost.
{"title":"Epidemiology of Kidney Disease in the United States: Highlights from the Centers for Disease Control and Prevention Kidney Disease Surveillance System.","authors":"Jennifer Bragg-Gresham,Fang Xu,Yun Han,Ana Laura Licon,Jenna Kiryakos,Michael Heung,Hal Morgenstern,William Weitzel,Tiffany Veinot,Brenda Gillespie,Zubin J Modi,William Herman,Tracey Pérez Koehlmoos,Robert Nee,James D Oliver,Sola Han,Meda E Pavkov,Rajiv Saran","doi":"10.2215/cjn.0000000867","DOIUrl":"https://doi.org/10.2215/cjn.0000000867","url":null,"abstract":"Kidney diseases are an important public health problem, rising in global significance. In place for nearly two decades, the Centers for Disease Control and Prevention's Kidney Disease Surveillance System (KDSS) is the first comprehensive surveillance system developed in the United States, focused exclusively on tracking kidney disease prior to end-stage kidney disease. The KDSS incorporates key data and trends from multiple, large national-level survey data sources (National Health and Nutrition Examination Survey), electronic medical record data (Military and Veterans Affairs Health Systems), health care claims (Medicare, Optum), and social determinants of health (American Community Survey). The prevalence of chronic kidney disease (CKD) among civilian US adults remains steady between 13%─14%. Prevalence is higher among older, female, non-Hispanic Black adults, and those with diabetes or hypertension. Among US veterans, the incidence of CKD and rates of diagnosis of acute kidney injury (AKI) increased from 2008 to 2022 (Incidence: 62.8 to 71.5/1,000 person-years, AKI: 84.9 to 241.7 cases/1,000 person-years. Awareness of the disease nationwide among persons with CKD has historically been low (<10%), but starting in 2013, has increased to approximately 25%. Persons with CKD self-report more problems with sleep, and those aged 65 and older self-report a higher prevalence of functional limitations. Improvements in quality-of-care measures, including medication prescription and increases in both serum creatinine and albuminuria testing were observed. Increased self-reported physical activity was observed among persons with CKD. Food insecurity increased among persons with CKD, with the highest prevalence in young, female, non-Hispanic Black, and Hispanic adults. While population-level prevalence of CKD remains stable, higher AKI and CKD rates are being observed in health systems settings. Robust surveillance is key to raising awareness of kidney disease, its risk factors, care quality, and outcomes. Surveillance findings may inform policy and evidence-based practices that reduce premature morbidity and mortality, improve quality of life, and reduce cost.","PeriodicalId":50681,"journal":{"name":"Clinical Journal of the American Society of Nephrology","volume":"80 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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