{"doi":"10.1159/000543327","title":"A New Model of Chronic Kidney Disease, Metabolic Derangements, and Heart Failure with Preserved Ejection Fraction in Aging Swine","abstract":"INTRODUCTION: Chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) are more prevalent in the elderly. There is a lack of large animal models that allow the study of the impact of age on CKD and HFpEF in a translational fashion. This manuscript reports the first large preclinical model of CKD-HFpEF and metabolic derangements in naturally aged swine. METHODS: CKD-HFpEF was induced in naturally aged (6-9 years old) and young (3 months old) pigs, followed for 14 weeks, and compared to normal young and old controls (n = 5/group). Renal and cardiac hemodynamics were quantified in vivo by multidetector-CT, echocardiography, and pressure-volume relationship studies. Renal and cardiac microvascular (MV) architecture (3D-micro-CT) and morphometric analysis (staining) were investigated ex vivo. RESULTS: Both young and old pigs developed CKD-HFpEF, but the renal, cardiac, and metabolic phenotype was accentuated in aging animals. Aging and CKD-HFpEF influenced fasting insulin levels and insulin resistance, glomerular filtration rate, cortical MV density, glomerulosclerosis, perivascular fibrosis, and tubular injury. Tubule-interstitial fibrosis and peritubular capillary density were influenced by aging, CKD-HFpEF, and their interaction (2-way ANOVA). Similarly, cardiac MV density, perivascular fibrosis, and myocardial remodeling were influenced by aging and CKD-HFpEF, and E/A by their interaction. Notably, renal and cardiac MV density correlated with renal and cardiac functional and structural changes. CONCLUSION: Our study establishes the first large animal model of aging CKD-HFpEF, allowing the investigation of age as a biological variable in cardiorenal and metabolic diseases. This new platform could foster new age-related research toward developing therapeutic interventions in CKD-HFpEF.","journal":"American Journal of Nephrology","year":2025,"id":530859,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7827,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":735167,"name":"Darla L. Tharp","orcid":"0009-0002-2543-2961","position":1,"is_corresponding":false},{"id":1244617,"name":"Rhys Sitz","orcid":null,"position":2,"is_corresponding":false},{"id":51251,"name":"Elizabeth A. McCarthy","orcid":"0000-0001-7321-9319","position":3,"is_corresponding":false},{"id":1411208,"name":"Kumar Shivam","orcid":null,"position":4,"is_corresponding":false},{"id":1098034,"name":"Sara Kazeminia","orcid":"0000-0002-2621-9962","position":5,"is_corresponding":false},{"id":318230,"name":"Alfonso Eirin","orcid":"0000-0002-3864-9644","position":6,"is_corresponding":false},{"id":428757,"name":"Alejandro Chade","orcid":"0000-0002-3672-3409","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39746326","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":[]}