{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(1)"],"submitter":["Inaba S"],"pubmed_abstract":["<h4>Background</h4>Chronic kidney disease (CKD) leads to premature mortality from cardiovascular events before kidney replacement therapy. Despite recognition of syndromes like cardiorenal anemia and cardiovascular-kidney-metabolic, predictive models for kidney and cardiovascular outcomes remain inadequate. This study aimed to develop a minimally invasive, risk model using circulating small extracellular vesicle-derived miRNAs among patients with CKD.<h4>Methods</h4>A derivation cohort (n=36) underwent microarray-based miRNA profiling, and a least absolute shrinkage and selection operator-penalized Cox proportional hazards model was constructed. Validation was performed using TaqMan quantitative polymerase chain reaction in a cohort of 234 patients with CKD without kidney replacement therapy. The primary outcome was a ≥30% reduction in estimated glomerular filtration rate or progression to kidney replacement therapy. The secondary outcome included all-cause mortality, kidney replacement therapy initiation, and major adverse cardiovascular events.<h4>Results</h4>In the derivation cohort, 36% of patients had hypertensive glomerulosclerosis as the underlying CKD cause, increasing to 48% in the validation cohort. Twenty-three miRNAs were significantly downregulated in advanced CKD, associated with cellular senescence, FOXO (forkhead box, class O) signaling, and cell cycle pathways. From these, 3 miRNAs-<i>hsa-let-7d-5p</i>, <i>hsa-miR-24-3p</i>, and <i>hsa-miR-126-3p</i>-were selected and integrated into the final risk score with cystatin C and urinary protein levels, following optimization in the validation cohort. Lower miRNA levels were linked to cardiovascular comorbidities and cardiorenal anemia syndrome. Over a median follow-up of 39 and 59 months, 108 kidney events and 70 composite outcomes occurred. The model effectively predicted adverse outcomes across CKD causes, further stratifying risk within cardiovascular-kidney-metabolic stage classifications.<h4>Conclusions</h4>Circulating small extracellular vesicle-derived miRNA profiles enable a noninvasive, longitudinally predictive model for adverse kidney and cardiovascular outcomes in CKD. This approach may improve early risk identification and clinical decision-making."],"journal":["Journal of the American Heart Association"],"pagination":["e045148"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12909002"],"repository":["biostudies-literature"],"pubmed_title":["Circulating Extracellular Vesicle MicroRNAs as Predictive Biomarkers for Kidney and Cardiovascular Events."],"pmcid":["PMC12909002"],"pubmed_authors":["Mori Y","Uchida S","Fujiki T","Hasegawa T","Koide T","Kikuchi H","Suzukawa R","Sekiya H","Arai Y","Inaba S","Naito S","Sohara E","Matsuki H","Susa K","Ando F","Iimori S","Nakano Y","Mori T","Mandai S"],"additional_accession":[]},"is_claimable":false,"name":"Circulating Extracellular Vesicle MicroRNAs as Predictive Biomarkers for Kidney and Cardiovascular Events.","description":"<h4>Background</h4>Chronic kidney disease (CKD) leads to premature mortality from cardiovascular events before kidney replacement therapy. Despite recognition of syndromes like cardiorenal anemia and cardiovascular-kidney-metabolic, predictive models for kidney and cardiovascular outcomes remain inadequate. This study aimed to develop a minimally invasive, risk model using circulating small extracellular vesicle-derived miRNAs among patients with CKD.<h4>Methods</h4>A derivation cohort (n=36) underwent microarray-based miRNA profiling, and a least absolute shrinkage and selection operator-penalized Cox proportional hazards model was constructed. Validation was performed using TaqMan quantitative polymerase chain reaction in a cohort of 234 patients with CKD without kidney replacement therapy. The primary outcome was a ≥30% reduction in estimated glomerular filtration rate or progression to kidney replacement therapy. The secondary outcome included all-cause mortality, kidney replacement therapy initiation, and major adverse cardiovascular events.<h4>Results</h4>In the derivation cohort, 36% of patients had hypertensive glomerulosclerosis as the underlying CKD cause, increasing to 48% in the validation cohort. Twenty-three miRNAs were significantly downregulated in advanced CKD, associated with cellular senescence, FOXO (forkhead box, class O) signaling, and cell cycle pathways. From these, 3 miRNAs-<i>hsa-let-7d-5p</i>, <i>hsa-miR-24-3p</i>, and <i>hsa-miR-126-3p</i>-were selected and integrated into the final risk score with cystatin C and urinary protein levels, following optimization in the validation cohort. Lower miRNA levels were linked to cardiovascular comorbidities and cardiorenal anemia syndrome. Over a median follow-up of 39 and 59 months, 108 kidney events and 70 composite outcomes occurred. The model effectively predicted adverse outcomes across CKD causes, further stratifying risk within cardiovascular-kidney-metabolic stage classifications.<h4>Conclusions</h4>Circulating small extracellular vesicle-derived miRNA profiles enable a noninvasive, longitudinally predictive model for adverse kidney and cardiovascular outcomes in CKD. This approach may improve early risk identification and clinical decision-making.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-07-07T03:08:56.619Z","creation":"2026-07-07T03:08:04.059Z"},"accession":"S-EPMC12909002","cross_references":{"pubmed":["41369156"],"doi":["10.1161/JAHA.125.045148"]}}