{"doi":"10.1093/ndt/gfaf009","title":"Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (macrophages, monocytes and T cells) infiltration and myofibroblast activation. An inflammatory to fibrotic transition corresponds with macrophage transition (M1–M2) associated with increased transforming growth factor (TGF)-β response. Chronic inflammation disrupts hemodynamic pathways, leading to imbalanced oxidative stress and the production of cytokines and growth factors that promote fibrotic stimulation, contributing to pathological cardiorenal remodeling. The inflammatory response paves the pre-fibrotic cardiorenal niche and drives subsequent fibrotic remodeling by activated myofibroblasts. A fibrotic cardiorenal response in CRS is characterized by increased and degradation-resistant deposition of extracellular proteins, especially fibrillar Collagen -I, -III and -V, and non-fibrillar Collagen-IV by active myofibroblasts. Recent advances in basic research animal models of CRS have advanced the knowledge of cardiorenal fibrosis. However, a significant need for clinical applications, trials and evaluation is still needed. Circulating biomarkers like procollagen peptides and TGF-β have clinically been associated with cardiorenal fibrosis diagnosis in CRS. Treatments targeting the fibrotic pathways have also shown efficacy in amelioration of cardiorenal fibrosis in preclinical models. Recent combination therapies targeting multiple fibrotic pathways have been shown to offer promising results. Thus, a understanding of the heterogenic pathological progression and fibrogenesis could identify novel therapeutic approaches for clinical CRS diagnosis and treatment.</jats:p>","journal":"Nephrology Dialysis Transplantation","year":2025,"id":640251,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1634497,"name":"Sanchari Chakraborty","orcid":null,"position":1,"is_corresponding":false},{"id":1135003,"name":"Antara Roy","orcid":"0009-0005-2696-4830","position":2,"is_corresponding":false},{"id":1195739,"name":"Anupam Mittal","orcid":null,"position":3,"is_corresponding":false},{"id":1634498,"name":"Trayambak Basak","orcid":null,"position":4,"is_corresponding":false},{"id":1663925,"name":"Abhi Dutta","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (macrophages, monocytes and T cells) infiltration and myofibroblast activation. An inflammatory to fibrotic transition corresponds with macrophage transition (M1–M2) associated with increased transforming growth factor (TGF)-β response. Chronic inflammation disrupts hemodynamic pathways, leading to imbalanced oxidative stress and the production of cytokines and growth factors that promote fibrotic stimulation, contributing to pathological cardiorenal remodeling. The inflammatory response paves the pre-fibrotic cardiorenal niche and drives subsequent fibrotic remodeling by activated myofibroblasts. A fibrotic cardiorenal response in CRS is characterized by increased and degradation-resistant deposition of extracellular proteins, especially fibrillar Collagen -I, -III and -V, and non-fibrillar Collagen-IV by active myofibroblasts. Recent advances in basic research animal models of CRS have advanced the knowledge of cardiorenal fibrosis. However, a significant need for clinical applications, trials and evaluation is still needed. Circulating biomarkers like procollagen peptides and TGF-β have clinically been associated with cardiorenal fibrosis diagnosis in CRS. Treatments targeting the fibrotic pathways have also shown efficacy in amelioration of cardiorenal fibrosis in preclinical models. Recent combination therapies targeting multiple fibrotic pathways have been shown to offer promising results. Thus, a understanding of the heterogenic pathological progression and fibrogenesis could identify novel therapeutic approaches for clinical CRS diagnosis and treatment.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39805714","pmcid":null,"openalex_id":"https://openalex.org/W4406318174","authors":[],"funders":[{"funder_name":"Indian Council of Medical Research","grant_id":"NCD/Adhoc/207/2022-2023","title":null}],"total_grants":1,"fwci":3.7952,"citation_percentile":0.92318871,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"closed","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfaf009/61430203/gfaf009.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/ndt/article-pdf/40/7/1273/61430203/gfaf009.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/ndt/gfaf009","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39805714","host_type":"repository"}],"fields_of_study":["Systemic Sclerosis and Related Diseases","Humans","Cardio-Renal Syndrome","Fibrosis","Animals","Kidney","Myocardium","Inflammation","Heart"],"mesh_terms":["Animals","Fibrosis","Heart","Humans","Inflammation","Kidney","Myocardium","Cardio-Renal Syndrome"],"keywords":["Medicine","Cardiorenal syndrome","Crosstalk","Fibrosis","Cardiology","Internal medicine","Cardiac fibrosis","Kidney","Heart failure","Inflammation","Matrix Remodeling","Collagens"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T09:15:10.759869Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}