Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis

Recent years have seen growing interest in the relationship between the heart and kidney disease, resulting in the general term cardiorenal syndrome (CRS) being coined for disorders involving both the heart and kidneys. However, no accurate animal model exists that can replicate the specific cardiorenal associations characteristic of the human CRS subtype. Preclinical studies published between 1990 and 2024 were identified from online electronic databases. These were reviewed and subjected to meta-analysis according to PRISMA, with the quality assessed using the SYRCLE tool. In total, the review and analysis included 251 papers discussing the rodent presentation of cardiorenal associations, expressed by various hemodynamic, echocardiographic and histopathologic parameters, and selected molecular hallmarks. A wide spectrum of invasive and non-invasive animal approaches has been proposed for CRS. Numerous approaches evoked cardiorenal impairments by elevating systemic pressure. Among the "one-hit" models, Dahl/SS and ISO-HF most commonly resulted in cardiac and renal alterations mimicking CRS-2, while DOCA-salt or STZ were the most likely to elicit cardiac injury in progression of renal failure. The clinical relevance of "two-hit" animal models of cardiorenal associations merits another study.