Nephrology Dialysis Transplantation最新文献

{"title":"Smoking cessation and atherosclerotic cardiovascular events and mortality in chronic kidney disease.","authors":"Young Su Joo, Hae-Ryoung Yun, Hyung Woo Kim, Hee Byung Koh, Chan-Young Jung, Tae-Ik Chang, Jung Tak Park, Sue Kyung Park, Young Youl Hyun, Yeong Hoon Kim, Suah Sung, Tae-Hyun Yoo, Kook-Hwan Oh, Shin-Wook Kang, Seung Hyeok Han","doi":"10.1093/ndt/gfae268","DOIUrl":"https://doi.org/10.1093/ndt/gfae268","url":null,"abstract":"<p><strong>Background: </strong>Smoking cessation is recommended to reduce excess atherosclerotic cardiovascular disease (ASCVD) and mortality in patients with chronic kidney disease (CKD). However, this recommendation is largely based on observational studies on the general population Therefore, we aimed to evaluate the association of smoking dose and smoking cessation duration with ASCVD and mortality in patients with CKD.</p><p><strong>Methods: </strong>We compiled a comprehensive pooled dataset comprising 66 245 participants with CKD from the KNOW-CKD and the UK Biobank cohort. Additionally, we included 307 353 participants without CKD from the UK Biobank cohort. Participants were categorized according to smoking dose and duration of smoking cessation base on a questionnaire. The primary outcome was a composite of ASCVD events or all-cause mortality.</p><p><strong>Results: </strong>Over a median follow-up period of 13.2 years, 14 671 (22.1%) participants reached the primary outcome. In the pooled CKD cohort, compared to never smokers, former and current smokers exhibited a 1.30- and 2.14-fold higher risk of the primary outcome, respectively. Among former smokers, the hazard ratios (HRs) (95% confidence intervals [CIs]) for smoking loads < 20 and ≥ 20 pack-years were 1.05 (1.00-1.10) and 2.14 (2.05-2.25), respectively. The increased risk of the primary outcome was attenuated by longer smoking cessation. The HRs (95% CIs) for smoking cessation of < 10 years, 10-20 years, and ≥ 20 years were 1.75 (1.65-1.86), 1.43 (1.34-1.52), and 1.11 (1.06-1.16), respectively, compared with never smokers. This association was also observed in individuals without CKD, but the risk was comparable between former smokers with smoking cessation ≥ 20 years and non-smokers, suggesting that a longer cessation is required in patients with CKD to offset the smoking-related adverse effects.</p><p><strong>Conclusions: </strong>Among former smokers with CKD, the risk of ASCVD or mortality was substantially attenuated with less smoking load and a longer duration of smoking cessation.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired and genetic determinants of disease phenotype and therapeutic strategies in C3 glomerulopathy and immunoglobulin-associated MPGN.","authors":"Marie-Sophie Meuleman, Julia Roquigny, Romain Brousse, Carine El Sissy, Guillaume Durieux, Moglie Le Quintrec, Jean-Paul Duong Van Huyen, Véronique Frémeaux-Bacchi, Sophie Chauvet","doi":"10.1093/ndt/gfae245","DOIUrl":"https://doi.org/10.1093/ndt/gfae245","url":null,"abstract":"<p><p>C3 glomerulopathy (C3G), a prototype of complement mediated disease, is characterized by significant heterogeneity, not only in terms of clinical, histological and biological presentation but also of prognosis, and response to existing therapies. Recent advancements in understanding the factors responsible for alternative pathway dysregulation in the disease have highlighted its even more complex nature. Here, we propose a reexamination of the diversity of C3G presentations in light of the drivers of complement activation. Autoantibodies targeting complement proteins, genetic abnormalities in complement genes and monoclonal immunoglobulins are now well-known to drive disease occurrence. This review discusses how these drivers contribute to the heterogeneity in disease phenotype and outcomes, providing insights into tailored diagnostic and therapeutic approaches. In recent years, a broad spectrum of complement inhibitory therapies has emerged, soon to be available in clinical practice. The recognition of specific clinical, biological, and histological patterns associated with different forms of C3G is crucial for personalized management, particularly treatment strategies.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired and genetic drivers of C3 and C5 convertase dysregulation in C3 glomerulopathy and immunoglobulin-associated MPGN.","authors":"Julia Roquigny, Marie-Sophie Meuleman, Carine El Sissy, Paula Vieira Martins, Seppo Meri, Anna Duval, Moglie Lequintrec, Fadi Fakhouri, Sophie Chauvet, Véronique Frémeaux-Bacchi","doi":"10.1093/ndt/gfae243","DOIUrl":"https://doi.org/10.1093/ndt/gfae243","url":null,"abstract":"<p><p>Dysregulation of the alternative pathway of complement plays a central role in the pathophysiology of C3 Glomerulopathy (C3G). Various autoimmune and genetic factors targeting the alternative pathway have been associated to both C3G and primary Immunoglobulin-associated Membranoproliferative Glomerulonephritis (Ig-MPGN), suggesting shared pathophysiological mechanisms. This review highlights the wide range of disease drivers identified that mainly target components or protein complexes of the alternative pathway, both in C3G and Ig-MPGN. Nephritic factors, which constitute a heterogeneous group of autoantibodies targeting the C3 or the C5 convertase, are the most common abnormalities. Monoclonal gammopathies are frequent in aging adults. They may promote complement activation and have in some cases also found to target alternative pathway regulatory proteins. Additionally, some patients with C3G and Ig-MPGN carry rare variants in genes encoding complement activating or regulating proteins of the alternative pathway. This review provides an informative overview of pathogenetic mechanisms associated with each abnormality, acting at different steps in the complement cascade. The diversity of targets involved in the C3G pathophysiology suggests the potential benefit of therapeutical approaches tailored to the underlying disease drivers, with a pivotal impact upstream or at the level of the C3 or C5 convertase activity.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective validation of initial eculizumab dosing in adults with atypical hemolytic uremic syndrome.","authors":"Mendy Ter Avest, Caroline Duineveld, Romy N Bouwmeester, Laura M Baas, Lambertus P W J van den Heuvel, Saskia M C Langemeijer, Jack F M Wetzels, Nicole C A J van de Kar, Rob Ter Heine","doi":"10.1093/ndt/gfae244","DOIUrl":"https://doi.org/10.1093/ndt/gfae244","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial.","authors":"Parminder K Judge, Katherine R Tuttle, Natalie Staplin, Sibylle J Hauske, Doreen Zhu, Rebecca Sardell, Lisa Cronin, Jennifer B Green, Nikita Agrawal, Ryoki Arimoto, Kaitlin J Mayne, Emily Sammons, Martina Brueckmann, Shimoli V Shah, Peter Rossing, Masaomi Nangaku, Martin J Landray, Christoph Wanner, Colin Baigent, Richard Haynes, William G Herrington","doi":"10.1093/ndt/gfae263","DOIUrl":"https://doi.org/10.1093/ndt/gfae263","url":null,"abstract":"<p><p>Patients with chronic kidney disease (CKD) are at risk of progressive loss of kidney function, heart failure, and cardiovascular death despite current proven therapies, including renin-angiotensin system inhibitors (RASi), sodium glucose co-transporter-2 inhibitors (SGLT2i), and statin-based regimens. RASi and SGLT2i reduce risk of CKD progression irrespective of primary cause of kidney disease, suggesting they target final common pathways. Targeting aldosterone overactivity with a nonsteroidal mineralocorticoid receptor antagonist (MRA) also reduces cardiorenal risk in patients with albuminuric diabetic kidney disease already treated with RASi. Together, these observations provide the rationale for trials to assess effects of inhibiting the aldosterone pathway in a broader range of patients with CKD, including those with non-diabetic causes of CKD or low albuminuria. Aldosterone synthase inhibitors (ASi) have emerged as an alternative to MRAs for aldosterone pathway inhibition. Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to-creatinine ratio by ∼40% compared to placebo with or without concurrent empagliflozin treatment. MRA and ASi increase risk of hyperkalaemia. Combining their use with an SGLT2i may mitigate some of this risk, improving tolerability, and allowing a wider range of patients to be treated (including those with higher levels of blood potassium than in previous trials). The EASi-KIDNEY (NCT06531824) double-blind placebo-controlled trial will test this approach by assessing the safety and cardiorenal efficacy of vicadrostat in combination with empagliflozin in ∼11,000 patients with CKD. It will be sufficiently large to assess effects in patients with and without diabetes separately.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte/macrophage pyroptosis and C5b-9-induced cyst enlargement in Pkd1-/- mice.","authors":"Yang Yang, Deyang Kong, Meihan Chen, Jiayi Lv, Jie Zhou, Cheng Xue, Shuwei Song, Minghui Song, Lu Ma, Zhiguo Mao, Changlin Mei","doi":"10.1093/ndt/gfae262","DOIUrl":"https://doi.org/10.1093/ndt/gfae262","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The levels of C5b-9, terminal products of complement activation, were significantly elevated in autosomal dominant polycystic kidney disease (ADPKD). However, the precise mechanisms by which C5b-9 facilitates cyst growth remain incompletely elucidated.</p><p><strong>Methods: </strong>Three groups of chronic-onset Pkd1-/- mice were established: one group received intravenous injections of 0.5 mg/kg C5b-9, another was administered 1.0 mg/kg monoclonal anti-C9 antibodies, and a control group received 1 mg/kg IgG isotype control (IC). All treatments were administered biweekly for two months (postnatal day [PD] 180-240). Renal macrophages from distinct subsets were sorted using fluorescence-activated cell sorting (FACS). To deplete macrophages, liposome clodronate (LC) was injected intraperitoneally. Sublethal irradiation followed by bone marrow (BM) reconstruction was performed in Pkd1-/- mice to evaluate the role of BM-derived macrophages (BMDMs) in ADPKD progression.</p><p><strong>Results: </strong>(1) In vitro, sublytic C5b-9 did not affect the viability of renal tubular epithelial cells (RTECs), but significantly induced M1-like polarization and pyroptosis of BMDMs. (2) In vivo, C5b-9 notably triggered pyroptosis of Ly6C+ monocytes and a reduction in circulating monocyte numbers as cysts enlarged. (3) Residual Ly6C+ monocytes infiltrated renal tissues and differentiated into Ly6C+ macrophages, which exhibited a greater susceptibility to pyroptosis compared to Ly6C- macrophages. (4) Although limited evidence has recently suggested that Ly6C- monocytes may also be affected by C5b-9, upregulation of CCR2 in Ly6C- macrophages was observed in C5b-9-treated Pkd1-/- mice, implying that Ly6C- monocytes could represent a significant source of M2 macrophages.</p><p><strong>Conclusions: </strong>C5b-9 infusion promoted RTEC proliferation by inducing pyroptosis of Ly6C+ monocytes/macrophages, contributing to progressive cyst enlargement in chronic-onset PKD mice.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam-Fernando José Carrera Carbó (1944-2024).","authors":"João M Frazão","doi":"10.1093/ndt/gfae246","DOIUrl":"https://doi.org/10.1093/ndt/gfae246","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker Guided Infliximab Therapy for Immune Checkpoint Inhibitor-induced Acute Interstitial Nephritis.","authors":"Elena-Bianca Barbir, Arjunmohan Mohan, Priscilla Koirala, Luis E Gutierrez, Callen D Giesen, John C Lieske, Sandra M Herrmann","doi":"10.1093/ndt/gfae257","DOIUrl":"https://doi.org/10.1093/ndt/gfae257","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics, treatment and disease burden among stage 3-4 chronic kidney disease patients with and without type 2 diabetes in Finland during 2016-2022.","authors":"Kaj Metsärinne, Johan Bodegård, Iiro Toppila, Kristiina Uusi-Rauva, Line Elmerdahl Frederiksen, Satu Brinkmann","doi":"10.1093/ndt/gfae242","DOIUrl":"https://doi.org/10.1093/ndt/gfae242","url":null,"abstract":"<p><strong>Background: </strong>Real-world evidence on the management of chronic kidney disease (CKD) with and without type 2 diabetes (T2D) is limited. This study described the characteristics, treatment, and disease burdenin patients with stage 3-4 CKD with and without T2D in Finland.</p><p><strong>Methods: </strong>This cohort study used data from primary and hospital care in five municipalities in Finland to identify adults with stage 3-4 CKD, defined as having either one estimated glomerular filtration rate (eGFR) measurement of 15-59 ml/min/1.73m2 followed by a second measurement taken ≥ 90 days apart, or a registered CKD diagnosis. Prevalence was determined on 31 December 2022, and a cohort of incident stage 3-4 CKD patients was followed from the first date fulfilling eligibility criteria since 01 January 2016 (index) until death or 31 December 2022, and analyzed by T2D status.</p><p><strong>Results: </strong>The prevalence of stage 3-4 CKD was 6.3%. Among the 12 474 incident stage 3-4 CKD patients, the majority were non-T2D (73%). The median age was similar for non-T2D and T2D CKD patients, respectively. Baseline albuminuria screening was 9% among non-T2D and 53% among T2D. The use of kidney-protective treatments at index was also lower in non-T2D patients (47%), compared with T2D patients (69%). The use of kidney-protective treatments remained unchanged during 12 months after index. Healthcare resource utilization was high, and CKD or heart failure contributed considerably more to the all-cause healthcare costs than atherosclerotic diseases, regardless of T2D status. In both CKD subgroups, 10% had died within one year.</p><p><strong>Conclusions: </strong>In Finland, CKD is highly prevalent and associated with high risks and low use of albuminuria testing and kidney-protective medications. Most CKD patients were non-T2D, which showed lower use of preventive management and similar risks compared with T2D patients. These findings call for an urgent need for improved awareness and risk management, especially in non-T2D CKD patients.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mineralocorticoid receptor antagonism attenuates arteriovenous fistula stenosis by modulating the phenotype of vascular smooth muscle cells.","authors":"Yamin Liu, Bohan Chen, Kai Chen, Yufei Wang, Chunyu Zhou, Xianhui Liang, Kai Wang, Pei Wang","doi":"10.1093/ndt/gfae247","DOIUrl":"https://doi.org/10.1093/ndt/gfae247","url":null,"abstract":"<p><strong>Background: </strong>Fistula stenosis is a primary contributor to arteriovenous fistula (AVF) failure in maintenance hemodialysis patients. Emerging data indicated excessive fibrotic remodeling was the primarily contributor to fistula stenosis during AVF remodeling. The mineralocorticoid receptor (MR) has been implicated in vascular remodeling across various cardiovascular pathologies. However, its role in AVF remodeling, particularly concerning fibrotic remodeling, remains elusive.</p><p><strong>Methods: </strong>MR expression and the phenotypes of vascular smooth muscle cells (VSMCs) were assessed in dysfunctional AVF. The effects of MR on VSMC phenotypic switching were examined in vitro, and the protective effects of MR antagonists on AVF outcome were evaluated in a rat AVF model.</p><p><strong>Results: </strong>Dysfunctional fistula exhibited significant medial fibrosis and extracellular matrix deposition, alongside markedly increased MR activity. In the dysfunctional fistula vessels, VSMC displayed reduced expression of the contractile marker SMMHC and featured characteristic of a synthetic phenotype, including increased osteopontin expression and heightened proliferation. In vitro studies with cultured VSMC revealed that MR overactivity induced by aldosterone led to phenotypic switching from contractile to synthetic state, concomitant with EGFR-ERK1/2 pathway overactivation. These effects were largely abolished by the MR antagonist fineronone. Knockdown of EGFR expression abrogated ERK1/2 phosphorylation and inhibited the VSMC phenotypic switching. Conversely, ectopic overexpression of EGFR in VSMC diminished the protective effect of finerenone. In rat AVF models, pharmacologic targeting of MR with finerenone significantly improved AVF outcomes, characterized by increased luminal diameters and flow volume, reduced medial fibrosis, and inhibited VSMC phenotypic switching. These beneficial outcomes were likely attributable to a restrained activity of EGFR-ERK1/2 pathway in VSMC and elevated NO production in endothelial cells.</p><p><strong>Conclusions: </strong>Our study demonstrated that therapeutic targeting of MR may improve AVF outcome by modulating VSMC phenotypic switching. These findings offer promising avenues for further clinical investigations aimed at optimizing AVF outcomes in the hemodialysis population.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}