Blood advances最新文献

{"title":"Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML.","authors":"Pau Montesinos, Dylan M Marchione, Christian Récher, Michael Heuser, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Marta Riva, Rodrigo T Calado, Andre C Schuh, Su-Peng Yeh, Adriana E Tron, Jianan Hui, Diego A Gianolio, Sung Choe, Prapti A Patel, Stéphane De Botton, Courtney D DiNardo, Hartmut Döhner","doi":"10.1182/bloodadvances.2025016399","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016399","url":null,"abstract":"<p><p>In the phase 3 AGILE study, after a 12.4-month median follow-up, ivosidenib, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, combined with azacitidine significantly improved event-free survival, overall survival (OS), and complete remission rates compared with placebo-azacitidine in patients with newly diagnosed IDH1-mutated acute myeloid leukemia who were unfit for intensive chemotherapy. This post hoc analysis reports long-term follow-up results from AGILE after a median follow-up of 28.6 months. Overall, 148 patients were randomized to receive ivosidenib-azacitidine (N=73) or placebo-azacitidine (N=75). Median OS was significantly longer with ivosidenib (29.3 months; 95% CI 13.2, not reached) than with placebo (7.9 months; 95% CI 4.1, 11.3; hazard ratio 0.42 [0.27, 0.65]; p<.0001). Hematologic recovery was faster, more durable, and conversion to transfusion independence (53.8% vs 17.1%; p=.0004) was more common with ivosidenib than with placebo. Of 33 ivosidenib-treated patients evaluable for molecular measurable residual disease (MRD), 10 converted to MRD negativity. Although OS did not differ significantly between MRD-negative and MRD-positive responders at the 0.1% variant allele frequency (VAF) threshold, MRD-negative patients had numerically longer survival. MRD status appeared more predictive of long-term OS when an exploratory 1% VAF threshold was applied. MRD response was not associated with IDH1 variant, VAF, inferred clonality, or number of baseline comutations. The previously reported safety profile was maintained. These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy-ineligible patients with IDH1-mutated AML. ClinicalTrials.gov registration ID: NCT03173248.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706363","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":"Measurable Residual Disease Detection after CAR-T May Predict Response in Patients with Large B-cell Lymphoma.","authors":"Nira Krasnow, Katie Maurer, Catherine Jiawen Song, Justin Rhoades, Kan Xiong, Andjela Crnjac, Timothy Blewett, Lily Gao, Heather Jacene, Reid W Merryman, Satyen H Gohil, Caitlyn Duffy, Liliana I Guerrero, Jamie Dela Cruz, Mikaela McDonough, Jacquelyn O Wolff, Robert A Redd, Mike Mattie, Brodie Miles, G Mike Makrigiorgos, Donna S Neuberg, Scott J Rodig, Philippe Armand, Caron A Jacobson, Viktor A Adalsteinsson, Catherine J Wu","doi":"10.1182/bloodadvances.2024015788","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015788","url":null,"abstract":"<p><p>Despite responses of chimeric antigen receptor (CAR)-T cells in relapsed/refractory (R/R) large B cell lymphoma (LBCL) patients, over half of patients eventually relapse. Methods to detect early disease persistence are needed to identify patients at high-risk of treatment failure. We recently developed MAESTRO, an ultrasensitive, tumor-informed measurable residual disease (MRD) assay, which can detect parts-per-million (ppm) levels of circulating tumor DNA (ctDNA) using minimal sequencing. We applied MAESTRO to 140 samples from 28 patients (15 durable responders at 12 months, 13 nonresponders) to identify treatment failure following axicabtagene ciloleucel (axi-cel) administered at our institution between 2018 and 2022. Responder and nonresponder patients had similar baseline tumor burden. By 1 week after infusion, responders had marked ctDNA reduction compared to nonresponders, p<0.001. At weeks 2 and 4, responders had ctDNA levels approaching 0 ppm, while nonresponders had persistence of ctDNA, each p<0.001. At day 0, 21% of patients had ctDNA fractions below 0.01%, hence these individuals would not have qualified for ctDNA monitoring with a less sensitive test. Our results confirm feasibility of highly sensitive MRD detection by ctDNA for early identification of patients at high risk of disease progression from axi-cel.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706364","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 IL7 receptor and the RAG complex are required for the onset of B-cell acute lymphoblastic leukemia.","authors":"Audrey Dauba, Emmanuelle Näser, Antoine Nouhaud, Eric Delabesse, Bastien Gerby, Ahmed Amine Khamlichi","doi":"10.1182/bloodadvances.2025016313","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016313","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706368","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":"Post-transfusion recovery, quality and metabolism of short and long-term stored platelets during controlled inflammation.","authors":"Stefan F van Wonderen, Floor L F van Baarle, Philippa G Phelp, Esther B Bulle, Amy Argabright, Sanne de Bruin, Anita M Tuip-de Boer, Chantal A Polet, Rombout B E van Amstel, Endry H T Lim, Jimmy Schenk, Anna-Linda L Peters, Robin van Bruggen, Julie A Reisz, Christie Vermeulen, Thomas R L Klei, Bart J Biemond, Marcella C A Müller, Angelo D'Alessandro, Alexander P J Vlaar","doi":"10.1182/bloodadvances.2025016853","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016853","url":null,"abstract":"<p><p>Platelet concentrates (PCs) are frequently used to prevent and treat bleeding in patients. However, their efficacy is reduced during inflammation as well as due to platelet storage lesion, including metabolomic shifts and changes in surface markers of stored PCs. This study aims to identify disparities between short-term and long-term stored PCs during controlled inflammation, focusing on distinct metabolic pathways, alterations in surface markers and post-transfusion recovery (PTR). Twenty-four male subjects received lipopolysaccharide (LPS) or saline as control following an autologous transfusion of either short-term (2 days stored) or long-term stored (7 days stored) PCs. Metabolomics and surface markers of these transfused PCs were assessed before transfusion using mass spectrometry and flow cytometry, respectively. Biotin-labeled platelets were used to assess surface markers after transfusion and determine PTR. Prior to transfusion, short-term stored PCs demonstrated increased glycolysis, pentose phosphate pathway activity, dense granule components (e.g., serotonine, adenosine diphosphate, epinephrine), and purine, arginine, and tryptophan metabolism. In contrast, long-term stored PCs exhibited elevated transsulfuration and taurine metabolism, along with higher levels of CD62P and CD63. During inflammation, a decreased PTR was found, particularly in long-term stored PCs. Higher expression of dense granule metabolite components and lower CD62P and lactate levels were correlated with improved PTR. Differences in metabolic pathways, surface markers, and PTR were identified between short-term and long-term stored PCs in a controlled human experiment - suggesting a preference for the use of short-term stored PCs during inflammation. This trial was registered at https://trialsearch.who.int/ as #NL-OMON26852.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706366","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":"Real-world outcomes of brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma: a CIBMTR analysis.","authors":"Nausheen Ahmed, Swetha Thiruvengadam, Mehdi Hamadani, Zhen-Huan Hu, Natalie S Grover, Mazyar Shadman, Frederick L Locke, James Gerson, Matthew J Frank, Lihua E Budde, Michael L Wang, Soyoung Kim, Matthew Bye, Mohamed A Kharfan-Dabaja, Craig S Sauter, Peiman Hematti, Cameron J Turtle, Sairah Ahmed, Amy Moskop, Brent R Logan, Ana Nunes, David M Dalton, Ioana Magdalena Kloos, Daniel Lee, Hairong Xu, Marcelo C Pasquini, Alex F Herrera","doi":"10.1182/bloodadvances.2024015014","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015014","url":null,"abstract":"<p><p>Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T-cell therapy approved for relapsed/refractory mantle cell lymphoma (r/r MCL). Here, we report real-world effectiveness and safety outcomes of brexu-cel in a prospective study of patients with r/r MCL, including subgroups based on prior treatment with Bruton's tyrosine kinase inhibitor, bendamustine, or autologous hematopoietic cell transplant (auto-HCT) and number of prior therapy lines, using Center for International Blood and Marrow Transplant Research registry data. A total of 476 patients with r/r MCL who received brexu-cel between July 2020 and December 2022 were included in the analysis. With a median follow-up of 13.5 months, the overall response rate was 91% and complete response rate was 82%. One-year overall survival and progression-free survival rates were 76% and 63%, respectively. One-year cumulative incidence of non-relapse mortality was 8%. Prior auto-HCT was associated with better duration of response within 6 months after infusion (hazard ratio [HR] 0.49; 95% confidence interval [CI], 0.28-0.85) but greater risk of immune effector cell-associated neurotoxicity syndrome (odds ratio [OR] 1.66; 95% CI, 1.06-2.60). Prior bendamustine was associated with increased risk of prolonged thrombocytopenia (OR 1.90; 95% CI, 1.13-3.21). In patients with 1-2 prior therapy lines, relapse or progression was less frequent compared with those with 3 or more prior lines (HR 0.64; 95% CI, 0.42-1.00). Collectively, our results suggest that real-world outcomes with brexu-cel were consistent with ZUMA-2, regardless of prior therapy type or number of prior therapy lines.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706367","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 Disrupted Adenosinergic Axis Facilitates Platelet Activation in APS: Exploring a Novel Therapeutic Target.","authors":"Somanathapura K NaveenKumar, Thalia G Newman, Bruna Mazetto Fonseca, Srilakshmi Yalavarthi, Mariane C Flores Nascimento, Kaitlyn Sabb, Katarina Kmetova, Emily Chong, Kavya Sugur, Caroline H Ranger, Megan P Tompkins, Cyrus Sarosh, Jacqueline A Madison, Ajay Tambralli, Jordan K Schaefer, Michael Holinstat, Yu Zuo, Jason S Knight","doi":"10.1182/bloodadvances.2025016162","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016162","url":null,"abstract":"<p><p>Platelet activation is a hallmark of antiphospholipid syndrome (APS). However, the mechanisms through which antiphospholipid antibodies activate platelets and the optimal way to inhibit this pathophysiology are still not fully understood. Extracellular adenosine, produced by the ectoenzyme CD73, activates cell-surface receptors to increase intracellular cAMP, raising the threshold for platelet activation. Here, we found that platelets from patients with APS exhibited lower CD73 activity and cAMP content than healthy controls. Platelet activation, as measured by the surface expression of CD62P and activated αIIbβ3, was negatively correlated with CD73 activity and cAMP content. Exposing healthy platelets to APS patient IgG in vitro significantly reduced CD73 activity and intracellular cAMP while simultaneously increasing activation markers. We identified critical roles for FcγRIIa, phospholipase C, and the Akt signaling pathway in platelet activation by APS IgG. We also tested whether various agents that boost intracellular cAMP could blunt APS IgG-induced platelet activation. Agonism of the adenosine 2A receptor (A2AR) and inhibition of phosphodiesterase 3 (PDE3) were both highly effective in this regard. In summary, a dysregulated adenosinergic axis appears to potentiate APS platelets for prothrombotic activation by antiphospholipid antibodies. A2AR agonists and PDE3 inhibitors may be useful strategies for restoring platelet homeostasis in APS.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706361","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":"HLA-E[pHLA-G] Complex Specific Monoclonal Antibody Enhancing NK Activity in Multiple Myeloma.","authors":"Muhammad Abu Ahmad, Olga Radinsky, Bar Kaufman, Kamran Waidha, Eman Gharra, Sharon Dim, Dinesh Babu Manikandan, Noa Ofir, Dirk Jäger, Marten Meyer, Moshe Elkabets, Kerry S Campbell, Miri Zektser, Roi Gazit, Ory Rouvio, Frank Momburg, Angel Porgador","doi":"10.1182/bloodadvances.2025016276","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016276","url":null,"abstract":"<p><p>HLA-E presenting the HLA-G leader peptide VMAPRTLFL (HLA-E[pHLA-G]) on tumor cells plays a crucial role in suppressing natural killer(NK) and cytotoxic CD8+ T cells through NKG2A interaction. While blocking HLA-E:NKG2A is a promising immune checkpoint(IC) approach in cancer therapy, toxicity remains a major clinical concern. We developed a novel immune checkpoint inhibitor(ICI) that selectively prevents HLA-E:NKG2A interaction, a monoclonal antibody(mAb) that selectively targets the HLA-E[pHLA-G] complex, distinguishing cancerous from non-cancerous cells. In clinical bone marrow samples from multiple myeloma(MM) patients, 4D7 specifically recognized tumor-associated HLA-E-peptide complexes. Using NK cells from healthy donors, 4D7 effectively blocked the HLA-E:NKG2A interaction and enhanced NKG2A-positive NK cell activity in autologous MM cell co-cultures. Importantly, 4D7 did not inhibit NKG2C-positive NK cells, preserving their activity. Even though NKG2C also interacts with HLA-E. In MM-bearing mice treated with human NK cells, 4D7 significantly reduced tumor growth. This targeted approach activates NK cells only against tumor cells presenting HLA-E-peptide complexes, potentially minimizing toxicity compared to current NKG2A inhibitors. The development of 4D7 highlights a promising advancement in immunotherapy for hematological malignancies, offering improved outcomes for MM patients and a foundation for broader application across cancer types.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706362","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":"Nivolumab in Combination with R-CHOP for Treatment-Naïve Diffuse Large B-Cell Lymphoma: An Evaluation of Safety and Efficacy.","authors":"Oluwatobi Odetola, Shuo Ma, Jane N Winter, Barbara Pro, Ishan Roy, Ping Xie, Bin Zhang, Qing Chen, George Koulogeorgas, Xinlei Mi, Ruohui Chen, Yangruijue Ma, Xiaodan Tang, Robert Bayer, Valerie Nelson, Habib Shaikh, Dean Tsarwhas, Faisal Saghir, Parameswaran Venugopal, Leo I Gordon, Reem Karmali","doi":"10.1182/bloodadvances.2025016298","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016298","url":null,"abstract":"<p><p>Approximately 20% of diffuse large B-cell lymphoma have aberrations involving the PD-L1/PD-L2 locus. This justifies the investigation of PD-1 checkpoint inhibitors in the frontline therapy setting in a bid to improve outcomes especially in patients with high-risk disease (antecedent low-grade lymphoma, MYC aberrancy, advanced staged disease, and intermediate/high risk IPI score). This Phase 1b study evaluated the safety and preliminary efficacy of combination nivolumab and R-CHOP using a priming approach. Upon establishing the maximum tolerated dose of nivolumab, treatment consisted of a lead-in phase with nivolumab 240 mg x 1 followed 2 weeks later by combination nivolumab-R-CHOP given every 3 weeks for 6 cycles. A total of 33 patients were enrolled, of which 25 and 22 pts were evaluable for toxicity and efficacy, respectively. Estimated 18-month OS and PFS were 95.4% & 72.7%, respectively. The observed therapy-related adverse events were not significantly different from previous reports each nivolumab and R-CHOP, respectively. Patient reported outcomes did not suggest that the addition of nivolumab to R-CHOP led to worse quality of life measures. Exploratory analysis of biologic correlates showed an exhausted T cell immunophenotype to be a predictor of progression and immunotoxicity while also suggesting the effectiveness of priming approach. NCT03704714.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706365","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":"Red blood cell aggregation within a blood clot causes platelet-independent clot shrinkage.","authors":"Alina D Peshkova, Ekaterina K Rednikova, Rafael R Khismatullin, Oleg V Kim, Vladimir R Muzykantov, Prashant K Purohit, Rustem I Litvinov, John W Weisel","doi":"10.1182/bloodadvances.2024015533","DOIUrl":"10.1182/bloodadvances.2024015533","url":null,"abstract":"<p><strong>Abstract: </strong>Platelet-driven blood clot contraction (retraction) is important for hemostasis and thrombosis. Red blood cells (RBCs) occupy approximately half of the clot volume, but their possible active contribution to contraction is unknown. The work was aimed at elucidating the ability of RBCs to promote clot shrinkage. To distinguish the effects of platelets and RBCs, we formed thrombin-induced clots from reconstituted human samples containing platelet-free plasma and platelet-depleted RBCs, followed by tracking the clot size. The clots before and after RBC-induced shrinkage were analyzed using histology and scanning electron microscopy. Tension developed in the RBC-containing plasma clots was measured with rheometry, and theoretical modeling was used to elucidate the clot shrinkage mechanisms. Platelet-depleted clots formed in the presence of RBCs exhibited >20% volume shrinkage within one hour. This process was insensitive to blebbistatin, latrunculin A, and abciximab. At a higher RBC count, clot shrinkage increased, whereas in the absence of RBCs no plasma clot shrinkage was observed. At low platelet counts, RBCs stimulated clot contraction proportionately to the platelet level. Inside the shrunken clots, RBCs formed aggregates. The average tensile force per 1 RBC was ∼120 ± 100 pN. Clots from purified fibrinogen formed in the presence of RBCs did not change in size, but underwent shrinkage in the presence of osmotically active dextran. Blood clot shrinkage can be caused by RBCs alone, and this effect is because of the RBC aggregation driven mainly by osmotic depletion. The RBC-induced clot shrinkage may reinforce platelet-driven blood clot contraction and promote clot compaction when there are few and/or dysfunctional platelets.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3418-3428"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973561","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":"Chronic kidney disease in adults with sickle cell trait: a systematic review and meta-analysis.","authors":"Yagahira E Castro-Sesquen, Gelida Barboza Justiniano, Diego J Aparcana-Granda, Andres R Aquino, Pierre Luckens Adelson, Ronald D Mondragón, John Kwagyan, Vimal K Derebail, Mehdi Nouraie, Santosh L Saraf, Marina Jerebtsova","doi":"10.1182/bloodadvances.2025015920","DOIUrl":"10.1182/bloodadvances.2025015920","url":null,"abstract":"<p><strong>Abstract: </strong>Sickle cell trait (SCT) may increase the risk of chronic kidney disease (CKD). We aimed to determine the pooled statistics of the association between SCT and CKD. Studies published up to May 2024 that were available on PubMed, Embase, Global Health Library, and Web of Science were screened. We included studies that reported odds ratios or hazard ratios (HRs) of CKD and/or end-stage renal disease (ESRD) and that compared adults with SCT to those without SCT. The risk of bias was evaluated using the Risk Of Bias In Nonrandomized Studies-of Exposures tool. The pooled SCT prevalence was calculated among patients with CKD/ESRD. A random-effects analysis was performed. Only studies with low or some concerns of bias were included, corresponding to 18 847 participants with SCT and 1 060 818 without SCT. Participants with SCT had higher odds of having an estimated glomerular filtration rate (eGFR) of ≤60 mL/min per 1.73 m2, proteinuria, and eGFR ≤60 mL/min per 1.73 m2 and/or proteinuria. The pooled prevalence of SCT among African American individuals with ESRD was 10%; however, the heterogeneity was very high (I2, 85.6%). There was a higher HR for ESRD in the studies that included both males and females than in the study that included only females, suggesting that males have a higher risk of ESRD. Controversial results were observed for the association of CKD with hypertension and diabetes. SCT increases the risk of developing CKD and ESRD. PROSPERO registration: CRD42021275274.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3644-3657"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961783","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}