Kidney international最新文献

{"title":"Insights from the BKEVER Trial comparing everolimus versus mycophenolate mofetil for BK Polyomavirus infection in kidney transplant recipients","authors":"Sophie Caillard ,&nbsp;Nicolas Meyer ,&nbsp;Morgane Solis ,&nbsp;Dominique Bertrand ,&nbsp;Maite Jaureguy ,&nbsp;Dany Anglicheau ,&nbsp;Laure Ecotiere ,&nbsp;Matthias Buchler ,&nbsp;Nicolas Bouvier ,&nbsp;Betoul Schvartz ,&nbsp;Jean Philippe Rerolle ,&nbsp;Anne Elisabeth Heng ,&nbsp;Lionel Couzi ,&nbsp;Agnes Duveau ,&nbsp;Emmanuel Morelon ,&nbsp;Yann LeMeur ,&nbsp;Léonard Golbin ,&nbsp;Eric Thervet ,&nbsp;Ilies Benotmane ,&nbsp;Samira Fafi-Kremer","doi":"10.1016/j.kint.2024.09.018","DOIUrl":"10.1016/j.kint.2024.09.018","url":null,"abstract":"<div><div>The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients (KTRs). All together, 130 KTRs presenting with BKPyV DNAemia were randomized 1:1 into two groups. The EVR group, in which mycophenolate mofetil (MMF) was replaced by EVR along with a decrease in calcineurin inhibitor trough levels and secondly the MMF group, in which the MMF dose was decreased by half along with a similar lowering of calcineurin inhibitor levels. The primary endpoint was the proportion of patients achieving viral clearance at six months. Secondary endpoints included the kinetics of BKPyV replication over time, the incidence of BKPyV-associated nephropathy, kidney graft function, the incidence of kidney graft rejection, and medication tolerability over two years. Significantly, BKPyV clearance was achieved in 55.7% of patients in the EVR group compared to 81.3% of patients in the MMF group at six months. The reduction in BKPyV DNA load was significantly more rapid in the MMF group. Calcineurin inhibitor trough levels were within expected target ranges and did not differ meaningfully between the two groups from randomization through month six. Two grafts were lost, and four patients died. Eleven patients in the EVR group and six patients in the MMF group developed biopsy-proven BKPyV nephropathy. Thus, in KTRs with BKPyV DNAemia, replacing MMF with EVR along with lowering calcineurin inhibitor levels did not lead to more frequent or faster clearance of BKPyV.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 338-347"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567310","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":"A randomized controlled trial evaluated the efficacy and safety of apixaban for prevention of recurrent thrombosis after thrombectomy of hemodialysis vascular access","authors":"Tsung-Yu Ko ,&nbsp;Chih-Cheng Wu ,&nbsp;Mu-Yang Hsieh ,&nbsp;Chung-Wei Yang ,&nbsp;Chi-Hung Cheng ,&nbsp;Chun-Kai Chen ,&nbsp;Hsien-Li Kao","doi":"10.1016/j.kint.2024.10.023","DOIUrl":"10.1016/j.kint.2024.10.023","url":null,"abstract":"<div><div>Dialysis vascular access thrombosis poses a substantial challenge for individuals undergoing hemodialysis. The efficacy and safety of apixaban, a direct oral coagulation factor Xa inhibitor, in preventing recurrent access thrombosis have yet to be explored. Here, a multicenter randomized control study (NCT04489849) enrolled hemodialysis patients to evaluate this who underwent successful endovascular thrombectomy within 48 hours. Participants were assigned to standard care or standard care plus apixaban, 2.5 mg twice daily for three months. The trial design involved open-label administration, with independent adjudication of endpoints. The primary efficacy endpoint was recurrent access thrombosis within three months after thrombectomy. A total of 186 patients with well-balanced baseline characteristics were enrolled, 93 randomized to the apixaban group and 93 to the control group. The apixaban group demonstrated a significantly lower rate of access thrombosis at three months than the control group (24.0% vs. 40.8%; hazard ratio, 0.52 [95% confidence interval 0.31–0.88]), along with a significantly better primary patency failure rate (32.2% vs. 49.5%, 0.57 [0.36–0.91]). Safety outcomes showed comparable death rates and major bleeding incidents but significantly higher incidence of minor bleeding in the apixaban group (22.6% vs. 7.5%). The effect of apixaban did not show interaction in subgroups of different access types, antiplatelet usage, severity of comorbidities, or history of thrombosis. Thus, apixaban effectively reduced the risk of recurrent thrombosis in hemodialysis vascular access post-thrombectomy. Despite a minor increase in bleeding adverse effects, the net clinical benefit favors the use of apixaban in this context.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 348-358"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647838","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":"In situ molecular profiles of glomerular cells by integrated imaging mass spectrometry and multiplexed immunofluorescence microscopy","authors":"Allison B. Esselman ,&nbsp;Felipe A. Moser ,&nbsp;Léonore E.M. Tideman ,&nbsp;Lukasz G. Migas ,&nbsp;Katerina V. Djambazova ,&nbsp;Madeline E. Colley ,&nbsp;Ellie L. Pingry ,&nbsp;Nathan Heath Patterson ,&nbsp;Melissa A. Farrow ,&nbsp;Haichun Yang ,&nbsp;Agnes B. Fogo ,&nbsp;Mark de Caestecker ,&nbsp;Raf Van de Plas ,&nbsp;Jeffrey M. Spraggins","doi":"10.1016/j.kint.2024.11.008","DOIUrl":"10.1016/j.kint.2024.11.008","url":null,"abstract":"<div><div>Glomeruli filter blood through the coordination of podocytes, mesangial cells, fenestrated endothelial cells, and the glomerular basement membrane. Cellular changes, such as podocyte loss, are associated with pathologies like diabetic kidney disease. However, little is known regarding the <em>in situ</em> molecular profiles of specific cell types and how these profiles change with disease. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is well-suited for untargeted tissue mapping of a wide range of molecular classes. Importantly, additional imaging modalities can be integrated with MALDI IMS to associate these biomolecular distributions to specific cell types. Here, we integrated workflow combining MALDI IMS and multiplexed immunofluorescence (MxIF) microscopy. High spatial resolution MALDI IMS (5 μm) was used to determine lipid distributions within human glomeruli from a normal portion of fresh-frozen kidney cancer nephrectomy tissue revealing intra-glomerular lipid heterogeneity. Mass spectrometric data were linked to specific glomerular cell types and substructures through new methods that enable MxIF microscopy to be performed on the same tissue section following MALDI IMS, without sacrificing signal quality from either modality. Machine learning approaches were combined enabling cell type segmentation and identification based on MxIF data. This was followed by mining of cell type or cluster-associated MALDI IMS signatures using classification and interpretable machine learning. This allowed automated discovery of spatially specific molecular markers for glomerular cell types and substructures as well as lipids correlated to deep and superficial glomeruli. Overall, our work establishes a toolbox for probing molecular signatures of glomerular cell types and substructures within tissue microenvironments providing a framework applicable to other kidney tissue features and organ systems.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 332-337"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Case | A rare cause of acute kidney injury and proteinuria","authors":"Siarhei Dzedzik ,&nbsp;Frank Cortazar ,&nbsp;Dominick Santoriello","doi":"10.1016/j.kint.2024.11.012","DOIUrl":"10.1016/j.kint.2024.11.012","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 365-366"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029071","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":"The membrane transporter SLC25A48 enables transport of choline into human mitochondria","authors":"Suraj Patil ,&nbsp;Oleg Borisov ,&nbsp;Nora Scherer ,&nbsp;Christophe Wirth ,&nbsp;Pascal Schlosser ,&nbsp;Matthias Wuttke ,&nbsp;Sandra Ehret ,&nbsp;Luciana Hannibal ,&nbsp;Kai-Uwe Eckardt ,&nbsp;Carola Hunte ,&nbsp;Björn Neubauer ,&nbsp;Anna Köttgen ,&nbsp;Michael Köttgen","doi":"10.1016/j.kint.2024.06.022","DOIUrl":"10.1016/j.kint.2024.06.022","url":null,"abstract":"<div><div>Choline has important physiological functions as a precursor for essential cell components, signaling molecules, phospholipids, and the neurotransmitter acetylcholine. Choline is a water-soluble charged molecule requiring transport proteins to cross biological membranes. Although transporters continue to be identified, membrane transport of choline is incompletely understood and knowledge about choline transport into intracellular organelles such as mitochondria remains limited. Here we show that SLC25A48 imports choline into human mitochondria. Human loss-of-function mutations in <em>SLC25A48</em> show impaired choline transport into mitochondria and are associated with elevated urine and plasma choline levels. Thus, our studies may have implications for understanding and treating conditions related to choline metabolism.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 296-301"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses","authors":"Søren B. Poulsen ,&nbsp;Sathish K. Murali ,&nbsp;Linto Thomas ,&nbsp;Adrienne Assmus ,&nbsp;Lena L. Rosenbæk ,&nbsp;Rikke Nielsen ,&nbsp;Henrik Dimke ,&nbsp;Timo Rieg ,&nbsp;Robert A. Fenton","doi":"10.1016/j.kint.2024.07.013","DOIUrl":"10.1016/j.kint.2024.07.013","url":null,"abstract":"<div><div>The sodium/proton exchanger-3 (NHE3) plays a major role in acid–base and extracellular volume regulation and is also implicated in calcium homeostasis. As calcium and phosphate balances are closely linked, we hypothesized that there was a functional link between kidney NHE3 activity, calcium, and phosphate balance. Therefore, we examined calcium and phosphate homeostasis in kidney tubule–specific NHE3 knockout mice (NHE3^loxloxPax8 mice). Compared to controls, these knockout mice were normocalcemic with no significant difference in urinary calcium excretion or parathyroid hormone levels. Thiazide-induced hypocalciuria was less pronounced in the knockout mice, in line with impaired proximal tubule calcium transport. Knockout mice had greater furosemide-induced calciuresis and distal tubule calcium transport pathways were enhanced. Despite lower levels of the sodium/phosphate cotransporters (NaPi)-2a and -2c, knockout mice had normal plasma phosphate, sodium-dependent ³²Phosphate uptake in proximal tubule membrane vesicles and urinary phosphate excretion. Intestinal phosphate uptake was unchanged. Low dietary phosphate reduced parathyroid hormone levels and increased NaPi-2a and -2c abundances in both genotypes, but NaPi-2c levels remained lower in the knockout mice. Gene expression profiling suggested proximal tubule remodeling in the knockout mice. Acutely, indirect NHE3 inhibition using the SGLT2 inhibitor empagliflozin did not affect urinary calcium and phosphate excretion. No differences in femoral bone density or architecture were detectable in the knockout mice. Thus, a role for kidney NHE3 in calcium homeostasis can be unraveled by diuretics, but NHE3 deletion in the kidneys has no major effects on overall calcium and phosphate homeostasis due, at least in part, to compensating mechanisms.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 280-295"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title Page","authors":"","doi":"10.1016/S0085-2538(24)00865-2","DOIUrl":"10.1016/S0085-2538(24)00865-2","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Page A3"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143097982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRAIL induces podocyte PANoptosis via death receptor 5 in diabetic kidney disease","authors":"Zhimei Lv ,&nbsp;Jinxiu Hu ,&nbsp;Hong Su ,&nbsp;Qun Yu ,&nbsp;Yating Lang ,&nbsp;Meilin Yang ,&nbsp;Xiaoting Fan ,&nbsp;Yue Liu ,&nbsp;Bing Liu ,&nbsp;Yanfang Zhao ,&nbsp;Cheng Wang ,&nbsp;Shangwei Lu ,&nbsp;Ning Shen ,&nbsp;Rong Wang","doi":"10.1016/j.kint.2024.10.026","DOIUrl":"10.1016/j.kint.2024.10.026","url":null,"abstract":"<div><div>Podocytes can undergo PANoptosis (apoptosis, pyroptosis, and necroptosis). Diabetic kidney disease (DKD) is the leading cause of kidney failure, and podocyte loss is a major event leading to the progression of DKD. Here, we compared single cell RNA sequencing (scRNA-seq) data between three normal and three DKD human kidney samples and found a significant increase of <em>TNFSF10</em> and <em>TNFRSF10B</em> expression in podocytes of patients with DKD. Tumor necrosis factor (TNF)-related apoptosis–inducing ligand (TRAIL), coded by <em>TNFSF10</em>, belongs to the TNF superfamily members and <em>TNFRSF10B</em> codes for death receptor 5 (DR5). We confirmed that expression of TRAIL and DR5 increased in podocytes of patients with DKD and correlated with the severity of DKD. <em>In vitro</em>, TNF-α stimulated TRAIL and DR5 expression in cultured human podocytes. Silence of TRAIL or DR5 by small interfering RNA alleviated TNF-α-stimulated podocytes PANoptosis, while overexpression of TRAIL, treatment with recombinant human TRAIL (rh-TRAIL) or the DR5 activator (Bioymifi) enhanced podocytes PANoptosis. <em>In vivo</em>, podocyte-specific deletion of <em>TNFSF10</em> or <em>TNFRSF10B</em> alleviated podocyte and glomerular injury in high fat diet and streptozotocin-induced obese diabetic mice and was associated with decreased podocyte PANoptosis. Conversely, the induction of <em>TNFSF10</em> overexpression specifically in podocytes exacerbated albuminuria and kidney injury in diabetic mice with increased podocyte PANoptosis. Additionally, administration of soluble DR5-Fc, an inhibitor of DR5, resulted in a marked reduction in albuminuria and glomerular injury in BTBR ob/ob mice. Our findings suggest a critical autocrine role of TRAIL/DR5 in inducing podocyte injury in DKD via activation of PANoptosis.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 317-331"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing anti-inflammatory therapies: leveraging glucocorticoid pathways for novel treatments","authors":"Valerie Etzrodt ,&nbsp;Huihui Huang ,&nbsp;Samir M. Parikh","doi":"10.1016/j.kint.2024.11.005","DOIUrl":"10.1016/j.kint.2024.11.005","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Pages 217-221"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668446","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":"Corrigendum to “KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis.” Kidney International 2024;105(3S):S71–S116","authors":"","doi":"10.1016/j.kint.2024.10.004","DOIUrl":"10.1016/j.kint.2024.10.004","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 2","pages":"Page 367"},"PeriodicalIF":14.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}