Integrated Cardiorenal Risk in Multimorbidity: Emerging Biomarkers, Prognostic Stratification, and Contemporary Therapeutic Strategies
Abstract
Cardiorenal syndrome represents a complex clinical condition resulting from bidirectional interactions between cardiac and renal dysfunction and is particularly relevant in patients with multimorbidity, in whom heart failure, chronic kidney disease, diabetes mellitus, hypertension, obesity, and vascular disease frequently coexist. This study analyzed current evidence regarding emerging biomarkers, prognostic stratification, and integrated therapeutic approaches in adult patients with cardiorenal syndrome and multimorbidity. A structured integrative review based on the Scientific Method was conducted using contemporary clinical guidelines, scientific statements, randomized controlled trials, observational studies, and biomarker investigations. The analysis focused on conventional parameters and emerging biomarkers associated with glomerular filtration, tubular injury, myocardial stress, inflammation, and fibrosis. Cystatin C showed its greatest relevance as a complementary marker of glomerular function, while NGAL and KIM-1 were predominantly associated with tubular injury. NT-proBNP was mainly related to myocardial stress and congestion, whereas sST2 and galectin-3 provided additional information regarding inflammatory and fibrotic remodeling. Prognostic assessment demonstrated that declining estimated glomerular filtration rate, increased albuminuria, persistent congestion, recurrent heart failure decompensation, biomarker abnormalities, and greater multimorbidity burden were consistently associated with adverse cardiorenal outcomes. Therapeutic evidence from major randomized trials showed that sodium–glucose cotransporter-2 inhibitors significantly reduced major kidney and cardiovascular events across broad chronic kidney disease populations, while finerenone demonstrated complementary renal and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease. The findings support a transition from isolated organ-based evaluation toward a multidimensional cardiorenal framework integrating renal function, cardiovascular status, metabolic disease, biomarker profiles, and therapeutic response. Emerging biomarkers may improve biological phenotyping but should currently complement rather than replace established clinical variables. Integrated, multidisciplinary management involving internal medicine, cardiology, and nephrology may provide a more coherent approach to risk stratification and individualized treatment in patients with complex cardiorenal disease.