Nephrology Dialysis Transplantation最新文献

{"title":"Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial.","authors":"Aylin Akifova, Klemens Budde, Kerstin Amann, Maike Buettner-Herold, Mira Choi, Michael Oellerich, Julia Beck, Kirsten Bornemann-Kolatzki, Ekkehard Schütz, Friederike Bachmann, Fabian Halleck, Ellen von Hoerschelmann, Nadine Koch, Eva Schrezenmeier, Evelyn Seelow, Johannes Waiser, Bianca Zukunft, Kai-Uwe Eckardt, Jan Halbritter, Ralph Kettritz, Covadonga López Del Moral, Nils Lachmann, Diana Stauch, Matthias Niemann, Danilo Schmidt, Philip F Halloran, Bilgin Osmanodja","doi":"10.1093/ndt/gfae282","DOIUrl":"10.1093/ndt/gfae282","url":null,"abstract":"<p><strong>Background: </strong>Donor-derived cell-free DNA (dd-cfDNA) shows good diagnostic performance for the detection of antibody-mediated rejection (AMR) in kidney transplant recipients (KTR). However, the clinical benefits of dd-cfDNA monitoring need to be established. Early diagnosis of AMR at potentially reversible stages may be increasingly important due to emerging treatment options for AMR. We hypothesized that monitoring dd-cfDNA in KTR with de novo donor-specific anti-HLA antibodies (dnDSA) and performing kidney biopsy in case of increased dd-cfDNA may reduce time to AMR diagnosis in comparison with clinical indication biopsy.</p><p><strong>Methods: </strong>In this diagnostic, single-center, open-label, randomized clinical trial, we assigned 40 KTR with prevalent dnDSA and estimated glomerular filtration rate ≥20 mL/min/1.73 m2, but without previous biopsy-proven AMR, to either dd-cfDNA-guided biopsy (intervention group) or clinician-guided biopsy (control group) over a 12-month period. In both groups, dd-cfDNA was assessed at inclusion and 1, 3, 6, 9 and 12 months. In the intervention group, dd-cfDNA >50 copies/mL indicated a biopsy. Biopsies for clinical indication could be performed at any point during the study period in both groups. A protocol biopsy was scheduled after 12 months for patients without dd-cfDNA-guided biopsy or clinical indication biopsy until study completion. The primary endpoint was time from study inclusion to diagnosis of active or chronic active AMR.</p><p><strong>Results: </strong>Thirty-nine of 40 patients had functioning grafts at study completion. From these, 26 patients underwent biopsy, 13 in each group. AMR was diagnosed earlier in the intervention group than in the control group [median 2.8 months, interquartile range (IQR) 1.7-5.3 vs median 14.5 months, IQR 13.3-16.7, P = .003]. Longitudinal dd-cfDNA monitoring had 77% positive predictive value and 85% negative predictive value for AMR.</p><p><strong>Conclusions: </strong>Dd-cfDNA-guided biopsy in KTR with prevalent dnDSA can reduce the time to AMR diagnosis and hereby expedite therapy initiation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT04897438.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1384-1395"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenging the narrative of Alport syndrome spectrum: no link with cystic phenotype.","authors":"Marie-Sophie Pagniez, Yannis Lombardi, Victor Fages, Romain Larrue, Timothée Laboux, Clémence Gatinois, Emmanuel Letavernier, Claire Rigothier, François Glowacki, Laurent Mesnard, Thomas Robert","doi":"10.1093/ndt/gfae290","DOIUrl":"10.1093/ndt/gfae290","url":null,"abstract":"<p><strong>Background: </strong>Alport syndromes (AS) are the second leading genetic cause of kidney failure. Whether the multiple kidney cysts (MKC) phenotype belongs to the AS spectrum remains debated.</p><p><strong>Methods: </strong>This multicenter retrospective study focused on patients genotyped with pathogenic COL4A3, COL4A4, or COL4A5 variants (classified as ACMG-AMP 4 or 5) between January 2011 and January 2023 across four French university hospitals. The study aimed to compare characteristics between two groups based on the presence or absence of MKC, defined by three or more cysts per kidney. The MKC group was compared to a control group with negative exome sequencing results for undetermined kidney disease (ES-UKD) to assess the association between MKC and AS.</p><p><strong>Results: </strong>Among the 257 AS patients included, 38 (14.8%) presented MKC without variation from hereditary cystic kidney panel. MKC showed a significant association with male gender (P = 0.004), cardiovascular risk factors, and loss of function variants (P = 0.012). Kidney failure onset appeared significantly later, by 6 years, in MKC patients (P = 0.035). Comparison with the ES-UKD (n = 990) control group showed no significant association between AS and MKC by univariate and multivariate analysis. Multivariate analysis identified patient age and male gender (P < 0.001) as factors linked to MKC.</p><p><strong>Conclusions: </strong>A 14.8% prevalence of MKC was found in our cohort of 257 patients with AS. MKC-AS patients exhibited clinical and histological characteristics akin to nephroangiosclerosis. Our comprehensive analysis, incorporating a sizable ES-UKD cohort, revealed no significant association between MKC and AS, thus questioning the inclusion of MKC within the spectrum of AS.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1408-1415"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854571","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":"Acid excretion is impaired in calcium oxalate stone formers.","authors":"Pedro H Imenez Silva, Nasser A Dhayat, Daniel G Fuster, Harald Seeger, Alexander Ritter, Thomas Ernandez, Florian Buchkremer, Beat Roth, Olivier Bonny, Isabel Rubio-Aliaga, Carsten A Wagner","doi":"10.1093/ndt/gfaf038","DOIUrl":"10.1093/ndt/gfaf038","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1433-1435"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infiltrative classical monocyte-derived and SPP1 lipid-associated macrophages mediate inflammation and fibrosis in ANCA-associated glomerulonephritis.","authors":"Yosta Vegting, Aldo Jongejan, Annette E Neele, Nike Claessen, Gal Sela, Koen H M Prange, Jesper Kers, Joris J T H Roelofs, Joost W van der Heijden, Onno J de Boer, Ester B M Remmerswaal, Liffert Vogt, Frederike J Bemelman, Menno P J de Winther, Perry D Moerland, Marc L Hilhorst","doi":"10.1093/ndt/gfae292","DOIUrl":"10.1093/ndt/gfae292","url":null,"abstract":"<p><strong>Background: </strong>Kidney macrophage infiltration is a histological hallmark of vasculitic lesions and is strongly linked to disease activity in anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN). The precise mechanisms by which kidney macrophages influence local inflammation and long-term damage remain largely unknown.</p><p><strong>Methods: </strong>Here, we investigate kidney macrophage diversity using single-cell transcriptome analysis of 25 485 freshly retrieved unfrozen, high-quality kidney CD45+ immune cells from five AGN patients during active disease, a lupus nephritis and a nephrectomy control. Detailed subclustering of myeloid cells was performed to identify disease-specific macrophage subtypes. Next, transcriptome differences between macrophage subsets and disease serotypes were assessed. Findings were validated by immunostainings of an extended cohort of kidney biopsies and flow cytometric analysis of peripheral blood monocytes.</p><p><strong>Results: </strong>Four main macrophage subsets were identified, including a classical monocyte-derived macrophage (MDM) subset expressing a chemotactic (CXCL2, CXCL3, CXCL8, CCL3) and pro-inflammatory (IL1β, TNF) set of markers and an osteopontin/SPP1+ lipid-associated macrophage (SPP1 LAMs) subtype exhibiting distinctive upregulation of fibrotic genesets. AGN samples revealed a markedly increased proportion of CD163+ macrophages, predominantly composed of classical MDMs, accompanied by resident-like C1Q macrophages, and SPP1 LAMs. An analogous trend was observed in the expansion of peripheral blood classical monocytes during active disease. The proteinase 3 (PR3)-AGN subtype exhibited heightened classical MDM and SPP1 LAM infiltration and markers of acute inflammation, while interferon signaling and markers of chronicity were reduced compared with myeloperoxidase-AGN.</p><p><strong>Conclusions: </strong>Our findings highlight the expression of inflammatory and fibrotic genes by kidney macrophage subsets in AGN. Classical monocyte dysregulation might contribute to inflammation in the pathogenesis of AGN. Targeting these specific monocyte/macrophage subsets may potentially control the inflammatory cascade and attenuate resulting fibrosis in AGN and kidney disease in general.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1416-1427"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854574","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":"Epidemiological and clinicopathological characteristics of vascular-limited renal AL amyloidosis.","authors":"Noémie Senot, Jean Baptiste Gibier, Marion Rabant, Emmanuel Esteve, Elsa Ferriere, Kathleen Dessaix, Magali Colombat, Helene Perrochia, Jerome Olagne, Jean Michel Goujon, Nicolas Wayolle, Mathieu Wemeau, Benjamin Carpentier, Pierre Pinson, Nathanael Beeker, Frank Bridoux, Camille Cohen","doi":"10.1093/ndt/gfae285","DOIUrl":"10.1093/ndt/gfae285","url":null,"abstract":"<p><strong>Background: </strong>Kidney involvement, along with cardiac disease, is the most frequent manifestation of systemic AL amyloidosis, usually resulting in nephrotic-range proteinuria. Rarely, deposits predominantly or exclusively affect the intrarenal arterioles or arteries, with these vascular-limited forms following a distinct clinical course, but very little is known about these forms. Our work planned to better characterize renal vascular-limited AL amyloidosis.</p><p><strong>Methods: </strong>By mining a French Paris hospital database, we found that this unusual phenotype accounts for approximatively 9% of renal AL amyloidosis cases. We retrospectively studied 35 patients with the renal vascular-limited variant of AL amyloidosis on kidney biopsy.</p><p><strong>Results: </strong>All showed predominant or only (n = 21) intra-renal vascular deposits, of lambda isotype in 63%. At diagnosis, median urine protein/creatinine ratio was 0.5 g/g, with serum creatinine of 181 (133-216) µmol/L and estimated glomerular filtration (eGFR) rate of 36.2 (24.3-49.6) mL/min/1.73 m2. Cardiac involvement was present in 67% of cases. A serum and/or urine monoclonal gammopathy was identified in all but one patient and 31 (88%) had an abnormal free light chain ratio. Among 28 treated patients, hematological and renal response rates were 75% (including deep hematological response in 43%) and 18%, respectively. Median time from diagnosis to renal event, defined be a composite criterion composed of end-stage renal disease or >40% decrease in eGFR, was 56 months. Median overall survival was 59 months-significantly longer in patients who achieved a deep hematological response (178 vs 20 months, P = .002).</p><p><strong>Conclusion: </strong>Renal vascular-limited AL amyloidosis is a probably underdiagnosed disease with markedly reduced eGFR, low-grade proteinuria and severe overall prognosis. Rapid achievement of a deep hematological response is required to preserve long-term renal and patient outcomes.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1396-1407"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818666","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":"Glucocorticoids-induced remission followed by rituximab as maintenance therapy for podocytopathy with minimal change lesions in adults.","authors":"Ling Wang, Yan Chen, Shihui Hou, Xinghong Liu, Fei Xiao, Huanzi Dai","doi":"10.1093/ndt/gfaf050","DOIUrl":"10.1093/ndt/gfaf050","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1436-1438"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early identification of CKD in patients with solitary functioning kidney.","authors":"Luigi Cirillo, Tommaso Mazzierli, Alessandra Bettiol, Andrea La Tessa, Marco Moscato, Samantha Innocenti, Elisa Buti, Carmela Errichiello, Marco Materassi, Catia Olianti, Lorenzo Masieri, Francesca Becherucci","doi":"10.1093/ndt/gfaf063","DOIUrl":"10.1093/ndt/gfaf063","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1439-1441"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic 2-week glecaprevir/pibrentasvir in hepatitis C positive-to-negative kidney transplantation.","authors":"Rebecca A Dieter, Aprajita Mattoo, Perry Hotchkis, Ian S Jaffe, Elaina P Weldon, Jonathan C Berger, Nicole M Ali, Robert A Montgomery, Bonnie E Lonze","doi":"10.1093/ndt/gfae271","DOIUrl":"10.1093/ndt/gfae271","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Hepatitis C virus (HCV) positive-to-negative kidney transplants require direct-acting antiviral therapy, but the optimal timing and duration remain unclear. We hypothesized that a 14-day prophylactic course of glecaprevir/pibrentasvir 300/120 mg (GLE/PIB) would be safe and effective at treating donor-derived HCV viremia.</p><p><strong>Methods: </strong>This was a prospective, single-center, single-arm, open-label pilot study. Twenty adult HCV-negative recipients of HCV nucleic acid amplification test positive deceased-donor kidneys (HCV positive-to-negative) received a 14-day course of GLE/PIB, with the first dose pretransplant. HCV RNA viral load (VL) was monitored on postoperative days (POD) 1, 3, 7, and 13. If VL was undetectable on POD 13, GLE/PIB was stopped, and if detectable, GLE/PIB was continued to complete an 8-week course. Surveillance monitoring continued after treatment to ensure sustained viral response (SVR). The primary outcome was efficacy of 14-day prophylactic GLE/PIB. Secondary outcomes included patient and allograft survival, the incidence, timing, and clearance of HCV viremia, and safety events.</p><p><strong>Results: </strong>Seven out of 20 subjects (35%) never developed detectable HCV viremia. Only one subject had a detectable, but nonquantifiable, VL on POD 13 and completed an 8-week course. All subjects achieved SVR 12 weeks post-treatment with no relapses through 1-year follow-up. Mean time to undetectable HCV RNA VL was 10.5 (±4.7) days and mean peak VL was 371 (±715) copies/mL. Six-month and 1-year patient and allograft survival were 100% and 95%.</p><p><strong>Conclusion: </strong>A 14-day course of prophylactic GLE/PIB is safe and effective for HCV positive-to-negative kidney transplants and may prevent HCV transmission or significantly reduce the VL for those with detectable transmission, allowing rapid clearance within 2 weeks.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1322-1331"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) may enhance eryptosis and increase erythrocyte osmotic fragility through potential activation of PIEZO1.","authors":"Beatriz Akemi Kondo Van Spitzenbergen, Gabriela Bohnen Andrade, Erika Sousa Dias, Júlia Bacarin Monte Alegre, Gabriela Ferreira Dias, Nadja Grobe, Andrea Novais Moreno-Amaral, Peter Kotanko","doi":"10.1093/ndt/gfae275","DOIUrl":"10.1093/ndt/gfae275","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>In patients with advanced CKD the lifespan of red blood cells (RBCs) is often shortened, a condition attributed to the 'uremic milieu.' We reported recently that the uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) shares structural similarities with Jedi1, a chemical activator of the mechanosensitive cation channel PIEZO1, whose activation increases calcium influx into cells. Against this backdrop, we hypothesized that CMPF may induce premature RBC death (eryptosis) through prolonged CMPF-induced activation of PIEZO1 located on RBCs. To test this hypothesis, we explored if CMPF, at concentrations found in uremia, interacts with PIEZO1 located on RBCs, increases intracellular calcium (icCa2+), and induces eryptosis.</p><p><strong>Methods: </strong>RBCs from healthy individuals were incubated with CMPF or Jedi1 (both at a concentration of 87 µM), in the presence or absence of the PIEZO1 inhibitor GsMTx-4 (2 µM). We challenged RBCs osmotically through incubation in solutions of NaCl at concentrations between 3.0 and 9.0 g/L and determined their osmotic fragility. Using flow cytometry, we quantified in incubated RBCs icCa2+ levels and phosphatidylserine exposure, a cellular marker of eryptosis.</p><p><strong>Results: </strong>Incubation of RBCs with CMPF and Jedi1 significantly increased RBC osmotic fragility, an effect prevented by GsMTx-4. At 6.0 g/L NaCl, incubation with CMPF and Jedi1 increased exposure of phosphatidylserine and elevated icCa2+ levels of RBCs, indicating increased eryptosis. Notably, at an isotonic NaCl concentration of 9.0 g/L, CMPF-but not Jedi1-significantly increased RBC phosphatidylserine exposure and icCa2+ levels; both effects were diminished by GsMTx-4.</p><p><strong>Conclusion: </strong>Our findings support the hypothesis that CMPF may function as an endogenous activator of PIEZO1, increase icCa2+ levels, trigger eryptosis, and, through this pathway, possibly shorten the RBC lifespan. To what extent these in vitro findings are operative in advanced CKD warrants clinical studies.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1342-1349"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD38 ligation in sepsis promotes nicotinamide phosphoribosyltransferase-mediated IL-6 production in kidney stromal cells.","authors":"Yuya Suzuki, Tadashi Otsuka, Yusuke Takahashi, Shingo Maruyama, Alexey Annenkov, Yasuhiro Kanda, Tomoya Katakai, Hirofumi Watanabe, Riuko Ohashi, Yoshikatsu Kaneko, Ichiei Narita","doi":"10.1093/ndt/gfae269","DOIUrl":"10.1093/ndt/gfae269","url":null,"abstract":"<p><strong>Background: </strong>Activated macrophages, pivotal for driving the immune response in sepsis, express high levels of CD38. Although the circulating levels of its ligand, CD31, increase in sepsis, the functions of CD38 and its ligation remain elusive. This study aimed to elucidate the impact of CD38 ligation on sepsis using single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq, respectively) to identify a novel therapeutic target for severe sepsis.</p><p><strong>Methods: </strong>We performed scRNA-seq analysis of mouse peritoneal immune cells to precisely identify cell types exhibiting increased CD38 expression upon exposure to lipopolysaccharide (LPS). Subsequently we induced CD38 ligation using a well-established agonistic anti-CD38 antibody in a mouse model of LPS-induced sepsis. We analysed its pathophysiological effects using kidney snRNA-seq. Finally, we performed histological analysis of septic tissues collected from patients to ensure consistency of our findings between mice and humans.</p><p><strong>Results: </strong>LPS stimulation upregulated CD38 expression in peritoneal macrophages. CD38 ligation significantly exacerbated LPS-induced inflammation in vivo, particularly in the kidneys. Kidney snRNA-seq analysis revealed that CD38 ligation induced interleukin (IL)-6 production in renal stromal cells via nicotinamide phosphoribosyltransferase (NAMPT) signalling originating from CD38-positive macrophages. NAMPT inhibition significantly ameliorated LPS-induced IL-6 production and kidney injury. Histological analysis of human septic tissues demonstrated upregulation of IL6 messenger RNA and NAMPT in renal stromal cells and CD38-positive macrophages, respectively.</p><p><strong>Conclusion: </strong>Our findings elucidate the implications of CD38 ligation in an LPS-induced sepsis model and uncover shared signalling pathways between mice and human sepsis. NAMPT signalling identified in this study may be a novel therapeutic target for mitigating systemic inflammation and kidney injury associated with severe sepsis.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1310-1321"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}