Kidney international最新文献

{"title":"Estimating GFR in Kidney Transplant Recipients: Considerations for Selecting Equations.","authors":"Krishna A Agarwal,Ogechi M Adingwupu,Hocine Tighiouart,Shiyuan Miao,Marc Froissart,Michael Mauer,Wei Yang,Vicente Torres,Martin de Borst,Goran Klintmalm,Emilio D Poggio,Peter Rossing,Ruben Velez,Anders Grubb,Andrew D Rule,Kamran Shaffi,Ashtar Chami,Andrew S Levey,Lesley A Inker","doi":"10.1016/j.kint.2024.07.035","DOIUrl":"https://doi.org/10.1016/j.kint.2024.07.035","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":19.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174732","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":"Targeted gene therapy for rare genetic kidney diseases.","authors":"Veenita Khare, Stephanie Cherqui","doi":"10.1016/j.kint.2024.07.034","DOIUrl":"https://doi.org/10.1016/j.kint.2024.07.034","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is one of the leading causes of mortality worldwide because of kidney failure and the associated challenges of its treatment including dialysis and kidney transplantation. About one-third of CKD cases are linked to inherited monogenic factors, making them suitable for potential gene therapy interventions. However, the intricate anatomical structure of the kidney poses a challenge, limiting the effectiveness of targeted gene delivery to the renal system. In this review, we explore the progress made in the field of targeted gene therapy approaches and their implications for rare genetic kidney disorders, examining preclinical studies and prospects for clinical application. In vivo gene therapy is most commonly used for kidney-targeted gene delivery and involves administering viral and non-viral vectors through various routes such as systemic, renal vein and renal arterial injections. Small nucleic acids have also been used in preclinical and clinical studies for treating certain kidney disorders. Unexpectedly, hematopoietic stem and progenitor cells have been used as an ex vivo gene therapy vehicle for kidney gene delivery, highlighting their ability to differentiate into macrophages within the kidney, forming tunneling nanotubes that can deliver genetic material and organelles to adjacent kidney cells, even across the basement membrane to target the proximal tubular cells. As gene therapy technologies continue to advance and our understanding of kidney biology deepens, there is hope for patients with genetic kidney disorders to eventually avoid kidney transplantation.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120162","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 phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.","authors":"Viknesh Selvarajah, Darren Robertson, Lars Hansen, Lutz Jermutus, Kirsten Smith, Angela Coggi, José Sánchez, Yi-Ting Chang, Hongtao Yu, Joanna Parkinson, Anis Khan, H Sophia Chung, Sonja Hess, Richard Dumas, Tabbatha Duck, Simran Jolly, Tom G Elliott, John Baker, Albert Lecube, Karl-Michael Derwahl, Russell Scott, Cristobal Morales, Carl Peters, Ronald Goldenberg, Victoria E R Parker, Hiddo J L Heerspink","doi":"10.1016/j.kint.2024.08.023","DOIUrl":"https://doi.org/10.1016/j.kint.2024.08.023","url":null,"abstract":"<p><p>Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD ,estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m² and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks treatment with standard of care plus subcutaneous cotadutide up-titrated to100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once-weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m², geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95%confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2Dand CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108748","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":"Cyclin-dependent kinase 4 drives cystic kidney disease in the absence of mTORC1 signaling activity.","authors":"Florian Grahammer, Bernhard Dumoulin, Ramila E Gulieva, Hui Wu, Yaoxian Xu, Nurgazy Sulaimanov, Frederic Arnold, Lukas Sandner, Tomke Cordts, Abhijeet Todkar, Pierre Moulin, Wilfried Reichardt, Victor G Puelles, Rafael Kramann, Benjamin S Freedman, Hauke Busch, Melanie Boerries, Gerd Walz, Tobias B Huber","doi":"10.1016/j.kint.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.kint.2024.08.021","url":null,"abstract":"<p><p>Progression of cystic kidney disease has been linked to activation of the mTORC1 signaling pathway. Yet the utility of mTORC1 inhibitors to treat patients with polycystic kidney disease remains controversial despite promising preclinical data. To define the cell intrinsic role of mTORC1 for cyst development, the mTORC1 subunit gene Raptor was selectively inactivated in kidney tubular cells lacking cilia due to simultaneous deletion of the kinesin family member gene Kif3A. In contrast to a rapid onset of cyst formation and kidney failure in mice with defective ciliogenesis, both kidney function, cyst formation discerned by magnetic resonance imaging and overall survival were strikingly improved in mice additionally lacking Raptor. However, these mice eventually succumbed to cystic kidney disease despite mTORC1 inactivation. In-depth transcriptome analysis revealed the rapid activation of other growth-promoting signaling pathways, overriding the effects of mTORC1 deletion and identified cyclin-dependent kinase (CDK) 4 as an alternate driver of cyst growth. Additional inhibition of CDK4-dependent signaling by the CDK4/6 inhibitor Palbociclib markedly slowed disease progression in mice and human organoid models of polycystic kidney disease and potentiated the effects of mTORC1 deletion/inhibition. Our findings indicate that cystic kidneys rapidly adopt bypass mechanisms typically observed in drug resistant cancers. Thus, future clinical trials need to consider combinatorial or sequential therapies to improve therapeutic efficacy in patients with cystic kidney disease.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108751","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, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope.","authors":"Satoshi Miyamoto, Hiddo J L Heerspink, Dick de Zeeuw, Kota Sakamoto, Michihiro Yoshida, Masao Toyoda, Daisuke Suzuki, Takashi Hatanaka, Tohru Nakamura, Shinji Kamei, Satoshi Murao, Kazuyuki Hida, Shinichiro Ando, Hiroaki Akai, Yasushi Takahashi, Munehiro Kitada, Hisashi Sugano, Tomokazu Nunoue, Akihiko Nakamura, Motofumi Sasaki, Tatsuaki Nakatou, Kei Fujimoto, Daiji Kawanami, Takashi Wada, Nobuyuki Miyatake, Hiromi Kuramoto, Kenichi Shikata","doi":"10.1016/j.kint.2024.08.019","DOIUrl":"https://doi.org/10.1016/j.kint.2024.08.019","url":null,"abstract":"<p><p>Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual's change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope).We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m² to receive canagliflozin or guideline-recommended treatment except for SGLT2inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, -30.8% (95% confidence interval -42.6 to -16.8). The between-group difference (canagliflozin group - control group) of change in eGFR slope (chronic - pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m² per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggest that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108749","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":"Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease.","authors":"Audrey Dumont, Mouad Hamzaoui, Déborah Groussard, Michèle Iacob, Dominique Bertrand, Isabelle Remy-Jouet, Mélanie Hanoy, Frank Le Roy, Laurence Chevalier, Christoph Enzensperger, Hans-Dieter Arndt, Sylvanie Renet, Anaïs Dumesnil, Emilie Lévêque, Thomas Duflot, Valéry Brunel, Aurore Michel-Després, Marie-Pierre Audrézet, Vincent Richard, Robinson Joannidès, Dominique Guerrot, Jérémy Bellien","doi":"10.1016/j.kint.2024.08.020","DOIUrl":"https://doi.org/10.1016/j.kint.2024.08.020","url":null,"abstract":"<p><p>Altered polycystin-mediated endothelial flow mechanosensitivity contributes to the development of hypertension and cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPKD). Stimulation of endothelial type 5 dopamine receptors (DR5) can acutely compensate for the endothelial consequences of polycystin deficiency, but the chronic impact of this approach must be evaluated in ADPKD. Nineteen patients with ADPKD on standard of care therapy were randomized to receive a 2-month treatment with the DR agonist rotigotine using transdermal patches, nine at 2 mg/24hours and ten at 4 mg/24hours or while ten were untreated. Rotigotine at the dose of 4 mg/24hours significantly increased nitric oxide release (nitrite levels from 10±30 to 46±34 nmol/L) and radial artery endothelium-dependent flow-mediated dilatation (from 16.4±6.3 to 22.5±7.3%) in response to hand skin heating. Systemic hemodynamics were not significantly modified but aplanation tonometry showed that rotigotine at 4 mg/24hours reduced aortic augmentation index and pulse pressure without affecting carotid-to femoral pulse wave velocity. Plasma creatinine and urea, urinary cyclic AMP, which contributes to cyst growth in ADPKD and copeptin, a surrogate marker of vasopressin, were not affected by rotigotine. In mice with a specific deletion of polycystin-1 in endothelial cells, chronic infusion of the peripheral DR5 agonist fenoldopam also improved mesenteric artery flow-mediated dilatation and reduced blood pressure. Thus, our study demonstrates that in patients with ADPKD, chronic administration of rotigotine improves conduit artery endothelial function through the restoration of flow-induced nitric oxide release as well as hemodynamics suggesting that endothelial DR5 activation may represent a promising pharmacological approach to prevent cardiovascular complications of ADPKD.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108750","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":"Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.","authors":"Peiqi Hu, Hong Xiao, Marco A Alba, Hannah M Atkins, Shenju Gou, Yanglin Hu, John C Gomez, Corey M Jania, Jessica R Martin, Thomas E Morrison, Stephen L Tilley, Mark T Heise, Claire M Doerschuk, Ronald J Falk, J Charles Jennette","doi":"10.1016/j.kint.2024.08.022","DOIUrl":"https://doi.org/10.1016/j.kint.2024.08.022","url":null,"abstract":"<p><p>Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108752","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":"Hair-straightening cosmetics containing glyoxylic acid induce crystalline nephropathy.","authors":"Thomas Robert, Ellie Tang, Jennifer Kervadec, Aurore Desmons, Jean-Yves Hautem, Jeremy Zaworski, Michel Daudon, Emmanuel Letavernier","doi":"10.1016/j.kint.2024.07.032","DOIUrl":"https://doi.org/10.1016/j.kint.2024.07.032","url":null,"abstract":"<p><p>We recently reported the case of a patient who experienced three consecutive episodes of acute kidney injury, all of them following a \"Brazilian\" hair-straightening treatment. The cream used for the straightening procedure contained glyoxylic acid. To examine possible underlying mechanisms causing kidney injury, four groups of mice were exposed to topical application of (i) the straightening product, (ii) a cream containing 10% glyoxylic acid, (iii) a cream containing 10% glycolic acid or (iv) a control cream. Application of glycolic acid slightly increased urine oxalate excretion, while glyoxylic acid and the straightening product dramatically increased urine oxalate excretion and caused calcium oxalate nephropathy after transcutaneous absorption. Thus, glyoxylic acid was presumptively absorbed through the skin, metabolized to oxalate and promoted crystallization of calcium oxalate in urine. Hence, cosmetic products containing glyoxylic acid may induce acute kidney injury and should be discontinued. Further studies are needed to investigate the metabolism of glycolic acid and glyoxylic acid following topical application.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093607","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 reliable clinical test for detection of membranous nephropathy antigens using laser microdissection and mass spectrometry.","authors":"Julie A Vrana, Jason D Theis, Peter J Wegwerth, Surendra Dasari, Benjamin Madden, Samih H Nasr, Mary Fidler, Ellen D McPhail, Fernando C Fervenza, Sanjeev Sethi","doi":"10.1016/j.kint.2024.07.031","DOIUrl":"https://doi.org/10.1016/j.kint.2024.07.031","url":null,"abstract":"<p><p>Membranous nephropathy (MN) results from accumulation of antigen-antibody immune-complexes along the subepithelial region of the glomerular basement membranes. Over the last years, 13 target antigens have been discovered and include PLA2R, THSD7A, EXT1 and EXT2, NELL1, SEMA3B, NCAM1, CNTN1, HTRA1, FAT1, PCDH7, NTNG1, PCSK6 and NDNF, accounting for 80-90% of MN antigens. MN associated with many of these antigens have distinctive clinicopathologic findings. It is important to accurately identify the antigen in MN. Immunohistochemical (IHC) and/or immunofluorescence (IF) methods are currently used to detect PLA2R, THSD7A, NELL1, SEMA3B and EXT1/EXT2. However, for the remaining antigens, IHC/IF methods do not exist and are not practical for detection. Here, we developed laser microdissection-based mass spectrometry methodology (LMD/MS) as a one-stop clinical test for the detection of MN antigens using paraffin-embedded kidney biopsy tissue. The LMD/MS test was validated in two steps. LMD/MS was used to detect the antigen in 75 cases of MN with known antigens and correctly identified the antigen in all these cases. Next, LMD/MS was used to identify the antigen in 61 MN cases where the antigen was unknown and identified one of the known antigens in 40 of 61 cases including many of the less common antigens. This lower-than-expected detection rate is explained by intentional enrichment of the cohort with PLA2R-negative MN. Overall, PLA2R was identified in 16.4%, one of the other antigens detected in 49.1%, and in the remaining 34.5% of cases, none of the above antigens was detected. Thus, LMD/MS is an extremely useful and reliable method for the detection of known MN antigens and possibly indicating an unknown MN antigen for eventual discovery.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093605","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":"Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN).","authors":"Valentin Goutaudier, Richard Danger, Rusan Ali Catar, Maud Racapé, Aurélie Philippe, Michelle Elias, Marc Raynaud, Olivier Aubert, Didier Bouton, François Girardin, Éric Vicaut, Sarhan Yaiche, Jacques Demotes, Harald Heidecke, Jean-Luc Taupin, Christine Randoux-Lebrun, Mohamad Zaidan, Emmanuelle Papuchon, Hoa Le Mai, Thi-Van-Ha Nguyen, Francesc Moreso, Thierry Berney, Jean Villard, Christophe Legendre, Duska Dragun, Vassilios Papalois, Luciano Potena, Magali Giral, Pierre-Antoine Gourraud, Sophie Brouard, Elena Crespo, Fabian Halleck, Klemens Budde, Oriol Bestard, Alexandre Loupy, Carmen Lefaucheur","doi":"10.1016/j.kint.2024.07.027","DOIUrl":"https://doi.org/10.1016/j.kint.2024.07.027","url":null,"abstract":"<p><p>Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093606","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}