Pub Date : 2024-04-24DOI: 10.1016/j.xkme.2024.100831
Alexander L. Bullen , Alma Fregoso-Leyva , Ronit Katz , Dorothy Leann Long , Katharine L. Cheung , Suzanne E. Judd , Orlando M. Gutierrez , Joachim H. Ix , Mary Cushman , Dena E. Rifkin
Rationale & Objective
Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes.
Study Design
Prospective cohort.
Setting & Participants
Participants in Biomarker Mediators of Racial Disparities in Risk Factors, a nested cohort from the REasons for Geographic And Racial Differences in Stroke study, with available stored serum and urine samples from baseline and second visits for biomarker measurement.
Exposure
Baseline log-transformed pro-NT/NMN.
Outcomes
Incident CKD, progressive estimated glomerular filtration rate (eGFR) decline, incident albuminuria, and incident kidney failure within median follow-up time of 9.4 years.
Analytical Approach
Logistic regression.
Results
Among 3,914 participants, the mean ± SD age was 64 ± 8 (SD) years, 48% were women, and 51% were Black. Median baseline eGFR was 90 (IQR, 77-102) mL/min/1.73 m2. Each SD higher of pro-NT/NMN was associated with 9% higher odds of progressive eGFR decline (OR, 1.09; 95% CI, 1.00-1.20). There was no association observed with incident CKD (OR, 1.10; 95% CI, 0.96-1.27), incident albuminuria (OR, 1.08; 95% CI, 0.96-1.22), or incident kidney failure (OR, 1.10; 95% CI, 0.83-1.46). There were no differences in results by race or sex.
Limitations
Single measurement of pro-NT/NMN and limited generalizability.
Conclusions
Higher pro-NT/NMN was associated with progressive eGFR decline but no other manifestations of kidney disease incidence.
Plain-Language Summary
Neurotensin is a peptide secreted by the small intestine in response to a meal. Higher levels of neurotensin and its stable precursor, proneurotensin/neuromedin N (pro-NT/NMN), have been associated with cardiovascular disease and type 2 diabetes mellitus, important risk factors for the development of kidney disease. Whether pro-NT/NMN is directly associated with kidney outcomes has been less studied and has been done so in largely homogenous cohorts of White participants. Using the REasons for Geographic And Racial Differences in Stroke study, we followed Black and White participants and evaluated the risk of developing kidney outcomes. We found that elevated levels of pro-NT/NMN were associated with kidney function decline. Pro-NT/NMN may help individuals who may benefit from closer monitoring of kidney function.
{"title":"Proneurotensin/Neuromedin N and Risk of Incident CKD and Other Kidney Outcomes in Community-Living Individuals: The REGARDS Study","authors":"Alexander L. Bullen , Alma Fregoso-Leyva , Ronit Katz , Dorothy Leann Long , Katharine L. Cheung , Suzanne E. Judd , Orlando M. Gutierrez , Joachim H. Ix , Mary Cushman , Dena E. Rifkin","doi":"10.1016/j.xkme.2024.100831","DOIUrl":"10.1016/j.xkme.2024.100831","url":null,"abstract":"<div><h3>Rationale & Objective</h3><p>Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes.</p></div><div><h3>Study Design</h3><p>Prospective cohort.</p></div><div><h3>Setting & Participants</h3><p>Participants in Biomarker Mediators of Racial Disparities in Risk Factors, a nested cohort from the REasons for Geographic And Racial Differences in Stroke study, with available stored serum and urine samples from baseline and second visits for biomarker measurement.</p></div><div><h3>Exposure</h3><p>Baseline log-transformed pro-NT/NMN.</p></div><div><h3>Outcomes</h3><p>Incident CKD, progressive estimated glomerular filtration rate (eGFR) decline, incident albuminuria, and incident kidney failure within median follow-up time of 9.4 years.</p></div><div><h3>Analytical Approach</h3><p>Logistic regression.</p></div><div><h3>Results</h3><p>Among 3,914 participants, the mean<!--> <!-->±<!--> <!-->SD age was 64<!--> <!-->±<!--> <!-->8 (SD) years, 48% were women, and 51% were Black. Median baseline eGFR was 90 (IQR, 77-102) mL/min/1.73<!--> <!-->m<sup>2</sup>. Each SD higher of pro-NT/NMN was associated with 9% higher odds of progressive eGFR decline (OR, 1.09; 95% CI, 1.00-1.20). There was no association observed with incident CKD (OR, 1.10; 95% CI, 0.96-1.27), incident albuminuria (OR, 1.08; 95% CI, 0.96-1.22), or incident kidney failure (OR, 1.10; 95% CI, 0.83-1.46). There were no differences in results by race or sex.</p></div><div><h3>Limitations</h3><p>Single measurement of pro-NT/NMN and limited generalizability.</p></div><div><h3>Conclusions</h3><p>Higher pro-NT/NMN was associated with progressive eGFR decline but no other manifestations of kidney disease incidence.</p></div><div><h3>Plain-Language Summary</h3><p>Neurotensin is a peptide secreted by the small intestine in response to a meal. Higher levels of neurotensin and its stable precursor, proneurotensin/neuromedin N (pro-NT/NMN), have been associated with cardiovascular disease and type 2 diabetes mellitus, important risk factors for the development of kidney disease. Whether pro-NT/NMN is directly associated with kidney outcomes has been less studied and has been done so in largely homogenous cohorts of White participants. Using the REasons for Geographic And Racial Differences in Stroke study, we followed Black and White participants and evaluated the risk of developing kidney outcomes. We found that elevated levels of pro-NT/NMN were associated with kidney function decline. Pro-NT/NMN may help individuals who may benefit from closer monitoring of kidney function.</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100831"},"PeriodicalIF":3.9,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000426/pdfft?md5=7ad0c198c6834e8031d4d4ea5f9aeb6e&pid=1-s2.0-S2590059524000426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140775618","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 : 2024-04-22DOI: 10.1016/j.xkme.2024.100830
Julio A. Lamprea-Montealegre , Abigail Shapiro , Natalie A.B. Bontrager , Dena E. Rifkin , Simerjot K. Jassal , Lucile Parker Gregg , Sankar D. Navaneethan , Krista Navarra , Michael G. Shlipak , Michelle M. Estrella , Virginia Wang
<div><h3>Rationale & Objective</h3><p>The measurement of cystatin C has been recommended to enhance chronic kidney disease (CKD) detection and risk stratification in clinical practice. This study gathered insights into the perceptions and experiences of clinical staff regarding the use of cystatin C in CKD detection within the Veterans Health Administration (VHA) system.</p></div><div><h3>Study Design</h3><p>A qualitative approach was employed to explore barriers and facilitators of clinical staff regarding the use of cystatin C in CKD detection within the VHA system. The Organizational Theory of Implementation Effectiveness informed the development of a semistructured interview guide.</p></div><div><h3>Setting & Participants</h3><p>Health care providers, nurses, and clinical pharmacists from the VHA systems in San Francisco, San Diego, and Houston were interviewed between October 2021 and May 2022.</p></div><div><h3>Exposures</h3><p>Participants' experiences with cystatin C testing.</p></div><div><h3>Outcomes</h3><p>Perceived barriers and facilitators to cystatin C testing.</p></div><div><h3>Analytical Approach</h3><p>Participant responses from individual interviews were analyzed by a multidisciplinary team using rapid qualitative analysis methods.</p></div><div><h3>Results</h3><p>Fourteen in-depth interviews were conducted across the 3 VHA systems. Ten of 11 providers worked in primary care. Five key barriers to using cystatin C for CKD detection were identified. These included lack of patient awareness of CKD testing, lack of provider awareness about cystatin C, knowledge barriers about cystatin C testing, unclear roles and ownership of CKD detection, and lack of clinic support to enhance CKD detection. Suggested interventions to overcome these barriers included educational and training programs, improved clinic workflows, and electronic health record aids to support CKD detection and use of cystatin C.</p></div><div><h3>Limitations</h3><p>The results may not be generalizable to other health care systems outside the VHA.</p></div><div><h3>Conclusions</h3><p>The findings indicate a need for targeted interventions such as educational and training programs, improved clinical workflows, and electronic health record aids to address barriers limiting the use of cystatin C in clinical practice for enhanced CKD detection.</p></div><div><h3>Plain-Language Summary</h3><p>This study assessed how clinical staff at the Veterans Health Administration (VHA) feel about using a test called cystatin C to help detect chronic kidney disease (CKD) earlier and more accurately. The research team spoke to healthcare providers, nurses, and clinical pharmacists in San Francisco, San Diego, and Houston between October 2021 and May 2022. We conducted 14 detailed interviews to understand the challenges and opportunities in using cystatin C for CKD detection. We found that participants often lacked awareness of CKD and the benefits of testing with cystatin C. There
研究原理与方法；目标胱抑素 C 的测定被推荐用于加强慢性肾脏病（CKD）的检测和临床实践中的风险分层。本研究收集了退伍军人健康管理局（VHA）系统内临床工作人员对使用胱抑素C检测慢性肾脏病的看法和经验。研究设计采用定性方法探讨了退伍军人健康管理局系统内临床工作人员对使用胱抑素C检测慢性肾脏病的障碍和促进因素。在 2021 年 10 月至 2022 年 5 月期间，研究人员对旧金山、圣地亚哥和休斯顿退伍军人管理局系统的医护人员、护士和临床药剂师进行了访谈。分析方法由一个多学科小组采用快速定性分析方法对个别访谈中参与者的回答进行分析。结果在 3 个退伍军人医疗保健系统中进行了 14 次深入访谈。11 位医疗服务提供者中有 10 位从事初级保健工作。确定了使用胱抑素 C 检测 CKD 的五个主要障碍。这些障碍包括患者对 CKD 检测缺乏认识、医疗服务提供者对胱抑素 C 缺乏认识、胱抑素 C 检测的知识障碍、CKD 检测的角色和所有权不明确以及缺乏诊所支持以加强 CKD 检测。为克服这些障碍而建议采取的干预措施包括教育和培训计划、改进诊所工作流程和电子健康记录辅助工具，以支持 CKD 检测和胱抑素 C 的使用。结论研究结果表明，有必要采取有针对性的干预措施，如教育和培训计划、改进临床工作流程和电子健康记录辅助工具，以解决临床实践中使用胱抑素 C 以提高 CKD 检测水平的障碍。2021 年 10 月至 2022 年 5 月期间，研究小组在旧金山、圣地亚哥和休斯顿采访了医疗服务提供者、护士和临床药剂师。我们进行了 14 次详细访谈，以了解使用胱抑素 C 检测 CKD 所面临的挑战和机遇。我们发现，参与者往往缺乏对 CKD 的认识，也不了解使用胱抑素 C 进行检测的益处。此外，他们对如何有效使用该检测方法的认识也存在差距，对由谁负责 CKD 检测也存在困惑，而且诊所内部需要更好地支持胱抑素 C 的使用。
{"title":"Cystatin C Use for CKD Detection in the Veterans Health Administration System: A Qualitative Study of Barriers and Facilitators","authors":"Julio A. Lamprea-Montealegre , Abigail Shapiro , Natalie A.B. Bontrager , Dena E. Rifkin , Simerjot K. Jassal , Lucile Parker Gregg , Sankar D. Navaneethan , Krista Navarra , Michael G. Shlipak , Michelle M. Estrella , Virginia Wang","doi":"10.1016/j.xkme.2024.100830","DOIUrl":"10.1016/j.xkme.2024.100830","url":null,"abstract":"<div><h3>Rationale & Objective</h3><p>The measurement of cystatin C has been recommended to enhance chronic kidney disease (CKD) detection and risk stratification in clinical practice. This study gathered insights into the perceptions and experiences of clinical staff regarding the use of cystatin C in CKD detection within the Veterans Health Administration (VHA) system.</p></div><div><h3>Study Design</h3><p>A qualitative approach was employed to explore barriers and facilitators of clinical staff regarding the use of cystatin C in CKD detection within the VHA system. The Organizational Theory of Implementation Effectiveness informed the development of a semistructured interview guide.</p></div><div><h3>Setting & Participants</h3><p>Health care providers, nurses, and clinical pharmacists from the VHA systems in San Francisco, San Diego, and Houston were interviewed between October 2021 and May 2022.</p></div><div><h3>Exposures</h3><p>Participants' experiences with cystatin C testing.</p></div><div><h3>Outcomes</h3><p>Perceived barriers and facilitators to cystatin C testing.</p></div><div><h3>Analytical Approach</h3><p>Participant responses from individual interviews were analyzed by a multidisciplinary team using rapid qualitative analysis methods.</p></div><div><h3>Results</h3><p>Fourteen in-depth interviews were conducted across the 3 VHA systems. Ten of 11 providers worked in primary care. Five key barriers to using cystatin C for CKD detection were identified. These included lack of patient awareness of CKD testing, lack of provider awareness about cystatin C, knowledge barriers about cystatin C testing, unclear roles and ownership of CKD detection, and lack of clinic support to enhance CKD detection. Suggested interventions to overcome these barriers included educational and training programs, improved clinic workflows, and electronic health record aids to support CKD detection and use of cystatin C.</p></div><div><h3>Limitations</h3><p>The results may not be generalizable to other health care systems outside the VHA.</p></div><div><h3>Conclusions</h3><p>The findings indicate a need for targeted interventions such as educational and training programs, improved clinical workflows, and electronic health record aids to address barriers limiting the use of cystatin C in clinical practice for enhanced CKD detection.</p></div><div><h3>Plain-Language Summary</h3><p>This study assessed how clinical staff at the Veterans Health Administration (VHA) feel about using a test called cystatin C to help detect chronic kidney disease (CKD) earlier and more accurately. The research team spoke to healthcare providers, nurses, and clinical pharmacists in San Francisco, San Diego, and Houston between October 2021 and May 2022. We conducted 14 detailed interviews to understand the challenges and opportunities in using cystatin C for CKD detection. We found that participants often lacked awareness of CKD and the benefits of testing with cystatin C. There","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100830"},"PeriodicalIF":3.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000414/pdfft?md5=f62bce0ebf263264571fdc25971176cc&pid=1-s2.0-S2590059524000414-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766276","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 : 2024-04-18DOI: 10.1016/j.xkme.2024.100829
Maria Gabriela Motta Guimarães , Fernanda Pinheiro Martin Tapioca , Naiara Rodrigues dos Santos , Fernanda Pitta do Carmo Tourinho Ferreira , Luiz Carlos Santana Passos , Paulo Novis Rocha
Rationale & Objective
The use of hemodiafiltration (HDF) as a kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD) has sparked a debate regarding its advantages over conventional hemodialysis (HD). The present study aims to shed light on this controversy by comparing mortality rates and cause-specific deaths between ESKD patients receiving HDF and those undergoing HD.
Study Design
Systematic review and meta-analysis of randomized controlled trials (RCTs). The search was conducted using PubMed, EMBASE, and Cochrane Central on July 1, 2023.
Setting & Participants
Adult patients with ESKD on regular KRT.
Exposure
Studies with participants undergoing HDF.
Outcomes
Primary outcomes were all-cause mortality, cardiovascular (CV) mortality, deaths related to infections, and kidney transplant. We also evaluated the endpoints for deaths related to malignancy, myocardial infarction, stroke, arrhythmias, and sudden death.
Analytical Approach
We included RCTs evaluating HDF versus HD. Crossover trials and studies with overlapping populations were excluded. Two authors independently extracted the data following predefined search criteria and quality assessment. The risk of bias was assessed with Cochrane’s RoB2 tool.
Results
We included 5 RCTs with 4,143 patients, of which 2,078 (50.1%) underwent HDF, whereas 2,065 (49.8%) were receiving HD. Overall, HDF was associated with a lower risk of all-cause mortality (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.73-0.91; P < 0.001; I2 = 7%) and a lower risk of CV-related deaths (RR, 0.75; 95% CI, 0.61-0.92; P = 0.007; I2 = 0%). The incidence of infection-related deaths was also significantly different between therapies (RR, 0.69; 95% CI, 0.50-0.95; P = 0.02; I2 = 26%).
Limitations
In individual studies, the HDF groups achieved varying levels of convection volume.
Conclusions
Compared with those undergoing HD, patients receiving HDF experienced a reduction in all-cause mortality, CV mortality, and infection-related mortality. These results provide compelling evidence supporting the use of HDF as a beneficial intervention in ESKD patients undergoing KRT.
{"title":"Hemodiafiltration versus Hemodialysis in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis","authors":"Maria Gabriela Motta Guimarães , Fernanda Pinheiro Martin Tapioca , Naiara Rodrigues dos Santos , Fernanda Pitta do Carmo Tourinho Ferreira , Luiz Carlos Santana Passos , Paulo Novis Rocha","doi":"10.1016/j.xkme.2024.100829","DOIUrl":"10.1016/j.xkme.2024.100829","url":null,"abstract":"<div><h3>Rationale & Objective</h3><p>The use of hemodiafiltration (HDF) as a kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD) has sparked a debate regarding its advantages over conventional hemodialysis (HD). The present study aims to shed light on this controversy by comparing mortality rates and cause-specific deaths between ESKD patients receiving HDF and those undergoing HD.</p></div><div><h3>Study Design</h3><p>Systematic review and meta-analysis of randomized controlled trials (RCTs). The search was conducted using PubMed, EMBASE, and Cochrane Central on July 1, 2023.</p></div><div><h3>Setting & Participants</h3><p>Adult patients with ESKD on regular KRT.</p></div><div><h3>Exposure</h3><p>Studies with participants undergoing HDF.</p></div><div><h3>Outcomes</h3><p>Primary outcomes were all-cause mortality, cardiovascular (CV) mortality, deaths related to infections, and kidney transplant. We also evaluated the endpoints for deaths related to malignancy, myocardial infarction, stroke, arrhythmias, and sudden death.</p></div><div><h3>Analytical Approach</h3><p>We included RCTs evaluating HDF versus HD. Crossover trials and studies with overlapping populations were excluded. Two authors independently extracted the data following predefined search criteria and quality assessment. The risk of bias was assessed with Cochrane’s RoB2 tool.</p></div><div><h3>Results</h3><p>We included 5 RCTs with 4,143 patients, of which 2,078 (50.1%) underwent HDF, whereas 2,065 (49.8%) were receiving HD. Overall, HDF was associated with a lower risk of all-cause mortality (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.73-0.91; <em>P</em> <!--><<!--> <!-->0.001; I<sup>2</sup> <!-->=<!--> <!-->7%) and a lower risk of CV-related deaths (RR, 0.75; 95% CI, 0.61-0.92; <em>P</em> <!-->=<!--> <!-->0.007; I<sup>2</sup> <!-->=<!--> <!-->0%). The incidence of infection-related deaths was also significantly different between therapies (RR, 0.69; 95% CI, 0.50-0.95; <em>P</em> <!-->=<!--> <!-->0.02; I<sup>2</sup> <!-->=<!--> <!-->26%).</p></div><div><h3>Limitations</h3><p>In individual studies, the HDF groups achieved varying levels of convection volume.</p></div><div><h3>Conclusions</h3><p>Compared with those undergoing HD, patients receiving HDF experienced a reduction in all-cause mortality, CV mortality, and infection-related mortality. These results provide compelling evidence supporting the use of HDF as a beneficial intervention in ESKD patients undergoing KRT.</p></div><div><h3>Registration</h3><p>Registered at PROSPERO: CRD42023438362.</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100829"},"PeriodicalIF":3.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000402/pdfft?md5=e3c3711e7e84ef736a4090316fd2ad24&pid=1-s2.0-S2590059524000402-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140763663","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}
<div><h3>Rationale & Objective</h3><p>Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India. Heavy metals are known ingredients in some of these formulations. We studied the spectrum of glomerular diseases in patients using CAM.</p></div><div><h3>Study Design</h3><p>Case series.</p></div><div><h3>Setting & Participants</h3><p>Patients with proteinuria or unexplained acute kidney injury, who underwent a kidney biopsy between May 2021 and September 2022, and who provided a history of recent CAM intake were included in the study. For patients enrolled prospectively, blood and urine samples were analyzed using mass spectrometry for the presence of mercury, lead, arsenic and cadmium. The CAM formulation, when available, was analyzed using inductively coupled plasma-optical emission spectroscopy.</p></div><div><h3>Results</h3><p>Twenty-eight patients were enrolled in the study, with a median duration of CAM intake of 4 months (interquartile range, 2-6 months). Heavy metal screening was performed in 17 patients, of whom 15 had elevated urine mercury levels, 10 had elevated blood mercury levels, and 1 had elevated blood and urine arsenic levels. Of the 6 CAM formulations that were analyzed, all had high levels of mercury. Kidney biopsy findings were membranous nephropathy (n<!--> <!-->=<!--> <!-->19), minimal change disease (n<!--> <!-->=<!--> <!-->8), and mesangial proliferative glomerulonephritis (n<!--> <!-->=<!--> <!-->1). Of the 19 patients with membranous nephropathy, 14 were associated with neural epidermal growth factor-like protein 1 (NELL-1). With conservative management alone, 17 patients achieved complete remission.</p></div><div><h3>Limitations</h3><p>Not all patients underwent blood and urine mercury testing, and only 6 patients provided the CAM samples for analysis. Furthermore, occupational and residential exposure to mercury could not be excluded.</p></div><div><h3>Conclusions</h3><p>The most common kidney pathology noted in our study was membranous nephropathy, which was predominantly associated with neural epidermal growth factor-like protein 1. A significant proportion of the patients recovered completely after withdrawal of the offending agent and initiation of renin-angiotensin system blockade.</p></div><div><h3>Plain Language Summary</h3><p>Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India, and heavy metals are known ingredients in some of these formulations. We describe the clinical spectrum of kidney disease, among patients who had recently ingested CAM. All patients underwent a kidney biopsy, and the most common finding was an entity called “NELL-1-associated membranous nephropathy,” which is known to be associated with heavy metal toxicity and CAM intake. Of 17 patients screened for such heavy metals, 15 had greater-than-permissible levels of mercury. Furthermore, 6 patients provided the CAM formulations that they had consumed for anal
{"title":"Complementary and Alternative Medicine Use and Glomerular Disease: A Contemporary Case Series","authors":"Prem Kumar Devaraju , Jayalakshmi Seshadri , Chelvamalai Muthukumaran Balasubramanian , Anila Abraham Kurien , Guhan Senthilkumaran , Vaishanavi Devi Rajarathinam , Vijayakumar Stanlybai Jibia , Vinoj Murugesan , Tanuj Moses Lamech , Dineshkumar Thanigachalam , Sakthirajan Ramanathan , Sheik Sulthan Alavudeen , Shivakumar Dakshinamoorthy , Seenivasan Mookaiah , Natarajan Gopalakrishnan","doi":"10.1016/j.xkme.2024.100827","DOIUrl":"https://doi.org/10.1016/j.xkme.2024.100827","url":null,"abstract":"<div><h3>Rationale & Objective</h3><p>Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India. Heavy metals are known ingredients in some of these formulations. We studied the spectrum of glomerular diseases in patients using CAM.</p></div><div><h3>Study Design</h3><p>Case series.</p></div><div><h3>Setting & Participants</h3><p>Patients with proteinuria or unexplained acute kidney injury, who underwent a kidney biopsy between May 2021 and September 2022, and who provided a history of recent CAM intake were included in the study. For patients enrolled prospectively, blood and urine samples were analyzed using mass spectrometry for the presence of mercury, lead, arsenic and cadmium. The CAM formulation, when available, was analyzed using inductively coupled plasma-optical emission spectroscopy.</p></div><div><h3>Results</h3><p>Twenty-eight patients were enrolled in the study, with a median duration of CAM intake of 4 months (interquartile range, 2-6 months). Heavy metal screening was performed in 17 patients, of whom 15 had elevated urine mercury levels, 10 had elevated blood mercury levels, and 1 had elevated blood and urine arsenic levels. Of the 6 CAM formulations that were analyzed, all had high levels of mercury. Kidney biopsy findings were membranous nephropathy (n<!--> <!-->=<!--> <!-->19), minimal change disease (n<!--> <!-->=<!--> <!-->8), and mesangial proliferative glomerulonephritis (n<!--> <!-->=<!--> <!-->1). Of the 19 patients with membranous nephropathy, 14 were associated with neural epidermal growth factor-like protein 1 (NELL-1). With conservative management alone, 17 patients achieved complete remission.</p></div><div><h3>Limitations</h3><p>Not all patients underwent blood and urine mercury testing, and only 6 patients provided the CAM samples for analysis. Furthermore, occupational and residential exposure to mercury could not be excluded.</p></div><div><h3>Conclusions</h3><p>The most common kidney pathology noted in our study was membranous nephropathy, which was predominantly associated with neural epidermal growth factor-like protein 1. A significant proportion of the patients recovered completely after withdrawal of the offending agent and initiation of renin-angiotensin system blockade.</p></div><div><h3>Plain Language Summary</h3><p>Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India, and heavy metals are known ingredients in some of these formulations. We describe the clinical spectrum of kidney disease, among patients who had recently ingested CAM. All patients underwent a kidney biopsy, and the most common finding was an entity called “NELL-1-associated membranous nephropathy,” which is known to be associated with heavy metal toxicity and CAM intake. Of 17 patients screened for such heavy metals, 15 had greater-than-permissible levels of mercury. Furthermore, 6 patients provided the CAM formulations that they had consumed for anal","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100827"},"PeriodicalIF":3.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000384/pdfft?md5=bae3d83b99a9605c9c8068d2e6b34e8b&pid=1-s2.0-S2590059524000384-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141068721","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 : 2024-04-17DOI: 10.1016/j.xkme.2024.100826
Marco Bonilla , Orhan Efe , Haresh Selvaskandan , Edgar V. Lerma , Nasim Wiegley
Focal segmental glomerulosclerosis (FSGS) defines a distinct histologic pattern observed in kidney tissue that is linked to several distinct underlying causes, all converging on the common factor of podocyte injury. It presents a considerable challenge in terms of classification because of its varied underlying causes and the limited correlation between histopathology and clinical outcomes. Critically, precise nomenclature is key to describe and delineate the pathogenesis, subsequently guiding the selection of suitable and precision therapies. A proposed pathomechanism-based approach has been suggested for FSGS classification. This approach differentiates among primary, secondary, genetic, and undetermined causes, aiming to provide clarity. Genetic FSGS from monogenic mutations can emerge during childhood or adulthood, and it is advisable to conduct genetic testing in cases in which there is a family history of chronic kidney disease, nephrotic syndrome, or resistance to treatment. Genome-wide association studies have identified several genetic risk variants, such as those in apolipoprotein L1 (APOL1), that play a role in the development of FSGS. Currently, no specific treatments have been approved to treat genetic FSGS; however, interventions targeting underlying cofactor deficiencies have shown potential in some cases. Furthermore, encouraging results have emerged from a phase 2 trial investigating inaxaplin, a novel small molecule APOL1 channel inhibitor, in APOL1-associated FSGS.
{"title":"A Review of Focal Segmental Glomerulosclerosis Classification With a Focus on Genetic Associations","authors":"Marco Bonilla , Orhan Efe , Haresh Selvaskandan , Edgar V. Lerma , Nasim Wiegley","doi":"10.1016/j.xkme.2024.100826","DOIUrl":"10.1016/j.xkme.2024.100826","url":null,"abstract":"<div><p>Focal segmental glomerulosclerosis (FSGS) defines a distinct histologic pattern observed in kidney tissue that is linked to several distinct underlying causes, all converging on the common factor of podocyte injury. It presents a considerable challenge in terms of classification because of its varied underlying causes and the limited correlation between histopathology and clinical outcomes. Critically, precise nomenclature is key to describe and delineate the pathogenesis, subsequently guiding the selection of suitable and precision therapies. A proposed pathomechanism-based approach has been suggested for FSGS classification. This approach differentiates among primary, secondary, genetic, and undetermined causes, aiming to provide clarity. Genetic FSGS from monogenic mutations can emerge during childhood or adulthood, and it is advisable to conduct genetic testing in cases in which there is a family history of chronic kidney disease, nephrotic syndrome, or resistance to treatment. Genome-wide association studies have identified several genetic risk variants, such as those in apolipoprotein L1 (<em>APOL1</em>), that play a role in the development of FSGS. Currently, no specific treatments have been approved to treat genetic FSGS; however, interventions targeting underlying cofactor deficiencies have shown potential in some cases. Furthermore, encouraging results have emerged from a phase 2 trial investigating inaxaplin, a novel small molecule APOL1 channel inhibitor, in <em>APOL1</em>-associated FSGS.</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100826"},"PeriodicalIF":3.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000372/pdfft?md5=94cd3108604d30cd53491d9615f30ee9&pid=1-s2.0-S2590059524000372-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140784394","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 : 2024-04-17DOI: 10.1016/j.xkme.2024.100828
Mona D. Doshi , Lihua Li , Abhijit S. Naik , Christie P. Thomas
<div><h3>Rationale & Objective</h3><p>The effect of apolipoprotein L1(<em>APOL1)</em> genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established.</p></div><div><h3>Study Design</h3><p>Longitudinal cohort study.</p></div><div><h3>Setting & Participants</h3><p>In total, 5,886 healthy individuals (45-64 years old) enrolled in the Atherosclerosis Risk in Communities study with creatinine-based estimated glomerular filtration rate<!--> <!-->≥<!--> <!-->80<!--> <!-->mL/min who would be suitable kidney donors.</p></div><div><h3>Exposures</h3><p>Race and <em>APOL1</em> genotype.</p></div><div><h3>Outcomes</h3><p>Creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2021 equation, urinary albumin-creatinine ratio (UACR), proportion with chronic kidney disease (CKD) 3a or worse, end-stage kidney disease (ESKD), and death.</p></div><div><h3>Analytical Approach</h3><p>Participants grouped based on race and <em>APOL1</em> genotype. Compared eGFRcr-cys and UACR across groups. Multinomial logistic regression models were used compare odds of CKD. Kaplan–Meier survival curves were created to compare rates of ESKD and death at last follow-up.</p></div><div><h3>Results</h3><p>There were 5,075 Whites (86%), 701 Blacks carrying the low-risk <em>APOL1</em> genotype (12%), and 110 Blacks carrying the high-risk A<em>POL1</em> genotype (2%). The mean age at baseline was 53<!--> <!-->±<!--> <!-->6 years. At 10 years, White participants had lower eGFRcr-cys than low-risk and high-risk groups (89<!--> <!-->±<!--> <!-->16 vs 91<!--> <!-->±<!--> <!-->16 and 92<!--> <!-->±<!--> <!-->15<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>, respectively; <em>P</em> <!--><<!--> <!-->0.001). At 25 years, White participants continued to have lower eGFRcr-cys than the low-risk group (70<!--> <!-->±<!--> <!-->18 vs 72<!--> <!-->±<!--> <!-->19<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>; <em>P</em> <!--><<!--> <!-->0.001) but not compared with the high-risk <em>APOL1</em> genotype (67±23<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>). There was no difference in UACR among groups at 10 and 25 years (<em>P</em> <!-->=<!--> <!-->0.87 and 0.91, respectively). The odds of developing CKD stage 3a or worse were not different between low-risk and high-risk <em>APOL1</em> group in both unadjusted and adjusted models (<em>P</em> <!-->=<!--> <!-->0.26 and <em>P</em> <!-->=<!--> <!-->0.39, respectively). At last follow-up,<!--> <!--><5% developed ESKD, and 45% of individuals either died or reached ESKD with no difference in outcomes between the groups.</p></div><div><h3>Limitations</h3><p>Low ascertainment because of death and long follow-up.</p></div><div><h3>Conclusions</h3><p>Among middle-aged individuals, <em>APOL1</em> genotype does not appear to be a major driver of future risk of kidney disease.</p></div><div><h3>Plain
{"title":"APOL1 Kidney Risk Variants and Long-Term Kidney Function in Healthy Middle-Aged Black Individuals: The Atherosclerosis Risk in Communities (ARIC) Study","authors":"Mona D. Doshi , Lihua Li , Abhijit S. Naik , Christie P. Thomas","doi":"10.1016/j.xkme.2024.100828","DOIUrl":"10.1016/j.xkme.2024.100828","url":null,"abstract":"<div><h3>Rationale & Objective</h3><p>The effect of apolipoprotein L1(<em>APOL1)</em> genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established.</p></div><div><h3>Study Design</h3><p>Longitudinal cohort study.</p></div><div><h3>Setting & Participants</h3><p>In total, 5,886 healthy individuals (45-64 years old) enrolled in the Atherosclerosis Risk in Communities study with creatinine-based estimated glomerular filtration rate<!--> <!-->≥<!--> <!-->80<!--> <!-->mL/min who would be suitable kidney donors.</p></div><div><h3>Exposures</h3><p>Race and <em>APOL1</em> genotype.</p></div><div><h3>Outcomes</h3><p>Creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2021 equation, urinary albumin-creatinine ratio (UACR), proportion with chronic kidney disease (CKD) 3a or worse, end-stage kidney disease (ESKD), and death.</p></div><div><h3>Analytical Approach</h3><p>Participants grouped based on race and <em>APOL1</em> genotype. Compared eGFRcr-cys and UACR across groups. Multinomial logistic regression models were used compare odds of CKD. Kaplan–Meier survival curves were created to compare rates of ESKD and death at last follow-up.</p></div><div><h3>Results</h3><p>There were 5,075 Whites (86%), 701 Blacks carrying the low-risk <em>APOL1</em> genotype (12%), and 110 Blacks carrying the high-risk A<em>POL1</em> genotype (2%). The mean age at baseline was 53<!--> <!-->±<!--> <!-->6 years. At 10 years, White participants had lower eGFRcr-cys than low-risk and high-risk groups (89<!--> <!-->±<!--> <!-->16 vs 91<!--> <!-->±<!--> <!-->16 and 92<!--> <!-->±<!--> <!-->15<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>, respectively; <em>P</em> <!--><<!--> <!-->0.001). At 25 years, White participants continued to have lower eGFRcr-cys than the low-risk group (70<!--> <!-->±<!--> <!-->18 vs 72<!--> <!-->±<!--> <!-->19<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>; <em>P</em> <!--><<!--> <!-->0.001) but not compared with the high-risk <em>APOL1</em> genotype (67±23<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>). There was no difference in UACR among groups at 10 and 25 years (<em>P</em> <!-->=<!--> <!-->0.87 and 0.91, respectively). The odds of developing CKD stage 3a or worse were not different between low-risk and high-risk <em>APOL1</em> group in both unadjusted and adjusted models (<em>P</em> <!-->=<!--> <!-->0.26 and <em>P</em> <!-->=<!--> <!-->0.39, respectively). At last follow-up,<!--> <!--><5% developed ESKD, and 45% of individuals either died or reached ESKD with no difference in outcomes between the groups.</p></div><div><h3>Limitations</h3><p>Low ascertainment because of death and long follow-up.</p></div><div><h3>Conclusions</h3><p>Among middle-aged individuals, <em>APOL1</em> genotype does not appear to be a major driver of future risk of kidney disease.</p></div><div><h3>Plain","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100828"},"PeriodicalIF":3.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000396/pdfft?md5=03c5acaccdbaa3b7d1081f33c667e315&pid=1-s2.0-S2590059524000396-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140794290","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 : 2024-04-16DOI: 10.1016/j.xkme.2024.100824
Jing Miao , Ramila A. Mehta , Andrea Kattah , Suzanne M. Norby , John C. Lieske , Dawn S. Milliner
Primary hyperoxaluria (PH) is a rare genetic disorder characterized by excessive oxalate production because of specific gene defects. PH1 is the most prevalent type, causing recurrent kidney stone disease and often leading to chronic kidney disease and kidney failure. Our previous study suggested that pregnancy did not adversely affect kidney function in female patients with PH. In this study, we identified 4 PH1 cases with urinary oxalate (UOx) measurements during pregnancy from the Rare Kidney Stone Consortium and Oxalosis and Hyperoxaluria Foundation PH registry to investigate UOx levels during pregnancy in patients with PH1. The PH Registry is approved by the Institutional Review Board of Mayo Clinic (Rochester, MN). All 4 showed a decrease in UOx during pregnancy when compared with before pregnancy and after delivery. These findings contrast with those of the general population, in which the UOx tends to increase during pregnancy because of a simultaneous physiological increase in the glomerular filtration rate. Elucidating the mechanism underlying reduced UOx during pregnancy in PH1 could suggest novel PH therapies. These findings could also affect the clinical management and have implications regarding the safety of withholding novel PH1-directed molecular therapies that currently have uncertain safety profiles during pregnancy. We highlight the need for additional data on urinary changes in patients with PH and other populations while pregnant to clarify changes in UOx throughout pregnancy.
{"title":"Urinary Oxalate Excretion During Pregnancy in Primary Hyperoxaluria Type 1: A Report of 4 Cases","authors":"Jing Miao , Ramila A. Mehta , Andrea Kattah , Suzanne M. Norby , John C. Lieske , Dawn S. Milliner","doi":"10.1016/j.xkme.2024.100824","DOIUrl":"10.1016/j.xkme.2024.100824","url":null,"abstract":"<div><p>Primary hyperoxaluria (PH) is a rare genetic disorder characterized by excessive oxalate production because of specific gene defects. PH1 is the most prevalent type, causing recurrent kidney stone disease and often leading to chronic kidney disease and kidney failure. Our previous study suggested that pregnancy did not adversely affect kidney function in female patients with PH. In this study, we identified 4 PH1 cases with urinary oxalate (UOx) measurements during pregnancy from the Rare Kidney Stone Consortium and Oxalosis and Hyperoxaluria Foundation PH registry to investigate UOx levels during pregnancy in patients with PH1. The PH Registry is approved by the Institutional Review Board of Mayo Clinic (Rochester, MN). All 4 showed a decrease in UOx during pregnancy when compared with before pregnancy and after delivery. These findings contrast with those of the general population, in which the UOx tends to increase during pregnancy because of a simultaneous physiological increase in the glomerular filtration rate. Elucidating the mechanism underlying reduced UOx during pregnancy in PH1 could suggest novel PH therapies. These findings could also affect the clinical management and have implications regarding the safety of withholding novel PH1-directed molecular therapies that currently have uncertain safety profiles during pregnancy. We highlight the need for additional data on urinary changes in patients with PH and other populations while pregnant to clarify changes in UOx throughout pregnancy.</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100824"},"PeriodicalIF":3.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000359/pdfft?md5=73a5ee830a46c3856615d37d3421b04a&pid=1-s2.0-S2590059524000359-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796584","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 : 2024-04-16DOI: 10.1016/j.xkme.2024.100825
Danira Medunjanin , Bethany J. Wolf , Roberto Pisoni , David J. Taber , John L. Pearce , Kelly J. Hunt
<div><h3>Rationale & Objective</h3><p>Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship.</p></div><div><h3>Study Design</h3><p>Retrospective cohort study.</p></div><div><h3>Setting & Participants</h3><p>24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to 2013.</p></div><div><h3>Exposures</h3><p>AKI, AKI severity, and age.</p></div><div><h3>Outcomes</h3><p>KFRT and death.</p></div><div><h3>Analytical Approach</h3><p>The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death.</p></div><div><h3>Results</h3><p>Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity.</p></div><div><h3>Limitations</h3><p>Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity.</p></div><div><h3>Conclusions</h3><p>In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.</p></div><div><h3>Plain Language Summary</h3><p>Older adults are at risk of acute kidney injury (AKI) and subsequent nonrecovery from AKI, resulting in long-term dialysis. Hospitalized patients have often been used in the past to study AKI. This could lead to biased conclusions when inferring from sicker populations. That is why we created a national cohort of 24,133 Veterans at least 65 years old with incident chronic kidney disease (CKD) stage 4 to examine the relationship between AKI and age and subsequent kidney failure with replacement therapy (KFRT). The data have showed that AKI and younger age are substantial risk factors for incident KFRT. As for older age, it appears to be protective against KFRT but not death. This is likely ex
理由与ampamp; 目标高龄是慢性肾脏病（CKD）发展的主要风险因素，而慢性肾脏病的发展具有高度异质性。急性肾损伤（AKI）住院率正在上升，尤其是在老年人中。以往的急性肾损伤流行病学分析主要针对住院人群，这可能会使分析结果偏向于病情较重的人群。本研究探讨了AKI与肾衰竭替代疗法（KFRT）之间的关系，同时评估了年龄对这一关系的调节作用。研究设计回顾性队列研究.研究地点及范围; 参与者24,133名退伍军人，年龄至少65岁，2011年至2013年期间发生CKD四期.暴露AKI、AKI严重程度和年龄.结果KFRT和死亡.分析方法Fine-Gray竞争风险回归用于模拟AKI和KFRT事件，死亡为竞争风险。结果尽管AKI和KFRT之间的年龄交互作用不显著，但观察到AKI和年龄对KFRT事件有临床相关的联合影响。与无 AKI 的最大年龄组相比，65-74 岁的 AKI 患者发生 KFRT 的风险最高（亚分布 HR [sHR]，14.9；95% CI，12.7-17.4），而至少 85 岁的 AKI 患者发生 KFRT 的风险最低（sHR，1.71；95% CI，1.22-2.39）。一旦退伍军人接受了 KFRT，他们的死亡风险就会增加 44%。在所有 AKI 严重程度分期中，KFRT 的风险都增加了 2 倍。局限性我们的研究缺乏普遍性，仅限于曾经使用过的药物，并使用住院患者的血清肌酐化验结果来定义 AKI 和 AKI 严重程度。这可能是因为在该人群中观察到的死亡频率较高（51.1%）。白话摘要老年人面临急性肾损伤（AKI）的风险，随后可能无法从 AKI 中恢复，导致长期透析。过去常常使用住院患者来研究 AKI。这可能会导致从病情较重的人群中推断出有偏差的结论。因此，我们建立了一个由 24,133 名至少 65 岁、患有慢性肾脏病 (CKD) 4 期的退伍军人组成的全国队列，以研究 AKI 与年龄和随后的肾衰替代治疗 (KFRT) 之间的关系。数据显示，AKI 和较年轻的年龄是发生 KFRT 的主要风险因素。至于年龄较大，似乎对 KFRT 有保护作用，但对死亡没有保护作用。这可能是由于在我们的队列中观察到的高死亡频率造成的。
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Pub Date : 2024-04-12DOI: 10.1016/j.xkme.2024.100823
Víctor J. Escudero-Saiz , Ángela Gonzalez , Adriana García-Herrera , Ana B. Larque , Andrew S. Bomback , Laura Morantes , Marta Martínez-Chillarón , Júlia Ollé , Elena Guillén , Marc Xipell , Alicia Molina-Andújar , Diana Rodríguez , Elena Cuadrado , Judit Cacho , Carolt Arana , Núria Esforzado , Carla Bastida , Esteban Poch , Fritz Diekman , David Cucchiari , Miquel Blasco
C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 “real-world” cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).
C3 肾小球病是一种罕见的疾病，由替代性补体途径的液相失调引起。目前，治疗方法取决于临床和组织学的严重程度，包括肾保护、非特异性免疫抑制和末端补体阻断剂（C5），但尚未批准病因治疗方法。C3 肾小球病在肾移植后的复发率很高，移植物丢失的风险也很高。幸运的是，目前正在开发专门针对近端替代补体途径的新分子，例如 B 因子抑制剂 iptacopan，在一项二期临床试验中，它在原生肾脏和移植复发病例中显示出良好的效果。我们介绍了两例接受伊帕考潘治疗的异体肾脏C3肾小球病复发的 "真实世界 "病例，这些病例最初的临床反应和安全性都非常好，尤其是在早期使用的情况下。我们还介绍了随访活检结果，结果显示因子 B 抑制期间没有 C3 沉积。我们的病例表明，近端阻断替代补体途径可有效、安全地治疗肾移植中的C3肾小球病复发，这也带来了其他问题，如双重阻断（如C3和C5）、从因子B抑制中获益的最佳患者情况或治疗持续时间，以及在其他形式的膜增生性肾小球肾炎（如免疫复合物介导的肾小球肾炎）中的潜在应用。
{"title":"Factor B Inhibition with Iptacopan in Recurrent C3 Glomerulopathy Following Kidney Transplant: A Report of Two Cases","authors":"Víctor J. Escudero-Saiz , Ángela Gonzalez , Adriana García-Herrera , Ana B. Larque , Andrew S. Bomback , Laura Morantes , Marta Martínez-Chillarón , Júlia Ollé , Elena Guillén , Marc Xipell , Alicia Molina-Andújar , Diana Rodríguez , Elena Cuadrado , Judit Cacho , Carolt Arana , Núria Esforzado , Carla Bastida , Esteban Poch , Fritz Diekman , David Cucchiari , Miquel Blasco","doi":"10.1016/j.xkme.2024.100823","DOIUrl":"10.1016/j.xkme.2024.100823","url":null,"abstract":"<div><p>C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 “real-world” cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100823"},"PeriodicalIF":3.9,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000347/pdfft?md5=b44683c9a22345d8860e8aacf690c347&pid=1-s2.0-S2590059524000347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140784489","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 : 2024-04-12DOI: 10.1016/j.xkme.2024.100822
Erik L. Lum , Jonathan E. Zuckerman , Lama Abdelnour , Jennifer Terenzini , Gurbir Singh , Suphamai Bunnapradist
Kidney transplant candidates with high anti–M-type phospholipase A2 receptor antibody activity may be at increased risk for early postkidney transplant recurrence and allograft loss. Pretransplant treatment to induce serological remission may be warranted to improve allograft survival. In this case report, a patient seeking their third kidney transplant, who lost 2 prior living donor transplants from early recurrent membranous nephropathy, underwent pretransplant treatment for membranous nephropathy with serological remission and no evidence of recurrent disease.
抗 M 型磷脂酶 A2 受体抗体活性较高的肾移植候选者可能会增加肾移植后早期复发和异体移植损失的风险。可能需要进行移植前治疗以诱导血清学缓解，从而提高异体移植的存活率。在本病例报告中，一名寻求第三次肾移植的患者曾因早期复发性膜性肾病而失去两次活体移植机会，在接受移植前膜性肾病治疗后血清学缓解，且无复发迹象。
{"title":"Pretransplant Treatment to Avoid Recurrent Membranous Nephropathy in a Kidney Transplant Recipient: A Case Report","authors":"Erik L. Lum , Jonathan E. Zuckerman , Lama Abdelnour , Jennifer Terenzini , Gurbir Singh , Suphamai Bunnapradist","doi":"10.1016/j.xkme.2024.100822","DOIUrl":"10.1016/j.xkme.2024.100822","url":null,"abstract":"<div><p>Kidney transplant candidates with high anti–M-type phospholipase A2 receptor antibody activity may be at increased risk for early postkidney transplant recurrence and allograft loss. Pretransplant treatment to induce serological remission may be warranted to improve allograft survival. In this case report, a patient seeking their third kidney transplant, who lost 2 prior living donor transplants from early recurrent membranous nephropathy, underwent pretransplant treatment for membranous nephropathy with serological remission and no evidence of recurrent disease.</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"6 6","pages":"Article 100822"},"PeriodicalIF":3.9,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000335/pdfft?md5=d3c1b89f91dbce73ccd3cf483f24a0e1&pid=1-s2.0-S2590059524000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140781630","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}
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