Integrated Cardiorenal Risk in Multimorbidity: Emerging Biomarkers, Prognostic Stratification, and Contemporary Therapeutic Strategies

Autores/as

DOI:

https://doi.org/10.64784/326

Palabras clave:

cardiorenal syndrome, multimorbidity, chronic kidney disease, heart failure, biomarkers, cystatin C, NGAL, KIM-1, sST2, galectin-3, prognostic stratification, SGLT2 inhibitors, finerenone, cardiovascular-kidney-metabolic syndrome, integrated treatment

Resumen

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.

Referencias

• Agarwal, R., Filippatos, G., Pitt, B., Anker, S. D., Rossing, P., Joseph, A., Kolkhof, P., Nowack, C., Gebel, M., Ruilope, L. M., & Bakris, G. L. (2022). Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: The FIDELITY pooled analysis. European Heart Journal, 43(6), 474–484. doi:10.1093/eurheartj/ehab777.

• Ajibowo, A. O., Okobi, O. E., Emore, E., Soladoye, E., Sike, C. G., Odoma, V. A., Bakare, I. O., Kolawole, O. A., Afolayan, A., Okobi, E., & Chukwu, C. (2023). Cardiorenal syndrome: A literature review. Cureus, 15(7), e41252. doi:10.7759/cureus.41252.

• Aletras, G., Bachlitzanaki, M., Stratinaki, M., Lamprogiannakis, E., Petrakis, I., Foukarakis, E., Pantazis, Y., Hamilos, M., & Stylianou, K. (2025). Integrating novel biomarkers into clinical practice: A practical framework for diagnosis and management of cardiorenal syndrome. Life, 15(10), 1540. doi:10.3390/life15101540.

• Bakris, G. L., Agarwal, R., Anker, S. D., Pitt, B., Ruilope, L. M., Rossing, P., Kolkhof, P., Nowack, C., Schloemer, P., Joseph, A., & Filippatos, G. (2020). Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. The New England Journal of Medicine, 383(23), 2219–2229. doi:10.1056/NEJMoa2025845.

• Chung, E. Y. M., Trinh, K., Li, J., Hahn, S. H., Endre, Z. H., Rogers, N. M., & Alexander, S. I. (2022). Biomarkers in cardiorenal syndrome and potential insights into novel therapeutics. Frontiers in Cardiovascular Medicine, 9, 868658. doi:10.3389/fcvm.2022.868658.

• EMPA-KIDNEY Collaborative Group. (2023). Empagliflozin in patients with chronic kidney disease. The New England Journal of Medicine, 388(2), 117–127. doi:10.1056/NEJMoa2204233.

• Gallo, G., Lanza, O., & Savoia, C. (2023). New insight in cardiorenal syndrome: From biomarkers to therapy. International Journal of Molecular Sciences, 24(6), 5089. doi:10.3390/ijms24065089.

• Gembillo, G., Visconti, L., Giusti, M. A., Siligato, R., Gallo, A., Santoro, D., & Mattina, A. (2021). Cardiorenal syndrome: New pathways and novel biomarkers. Biomolecules, 11(11), 1581. doi:10.3390/biom11111581.

• Heerspink, H. J. L., Stefánsson, B. V., Correa-Rotter, R., Chertow, G. M., Greene, T., Hou, F.-F., Mann, J. F. E., McMurray, J. J. V., Lindberg, M., Rossing, P., Sjöström, C. D., Toto, R. D., Langkilde, A.-M., & Wheeler, D. C. (2020). Dapagliflozin in patients with chronic kidney disease. The New England Journal of Medicine, 383(15), 1436–1446. doi:10.1056/NEJMoa2024816.

• Jefferies, J. L., Kovesdy, C. P., & Ronco, C. (2023). Contemporary laboratory assessment of acute cardiorenal syndrome for early diagnosis: A call for action. American Heart Journal, 261, 75–84. doi:10.1016/j.ahj.2023.03.007.

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. (2024). KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International, 105(4S), S117–S314. doi:10.1016/j.kint.2023.10.018.

• McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., Cleland, J. G. F., Crespo-Leiro, M. G., Farmakis, D., Gilard, M., Heymans, S., Hoes, A. W., Jaarsma, T., Jankowska, E. A., Lainscak, M., … Skibelund, A. K. (2023). 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal, 44(37), 3627–3639. doi:10.1093/eurheartj/ehad195.

• Ndumele, C. E., Neeland, I. J., Tuttle, K. R., Chow, S. L., Mathew, R. O., Khan, S. S., Coresh, J., Baker-Smith, C. M., Carnethon, M. R., Després, J.-P., Ho, J. E., Joseph, J. J., Kernan, W. N., Khera, A., Kosiborod, M. N., Lekavich, C. L., Lewis, E. F., Lo, K. B., Ozkan, B., … Rangaswami, J. (2023). A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic syndrome: A scientific statement from the American Heart Association. Circulation, 148(20), 1636–1664. doi:10.1161/CIR.0000000000001186.

• Ohlsson, M. A., Molvin, J., Isholth, H. H., Nezami, Z., Laucyte-Cibulskiene, A., Christensson, A., Jujic, A., & Magnusson, M. (2025). Biomarkers associated with worsening renal function and progression in chronic kidney disease among patients hospitalized for acute heart failure. Cardiorenal Medicine, 15(1), 453–461. doi:10.1159/000546236.

• Ostrominski, J. W., Neuen, B. L., Claggett, B., Filippatos, G., Desai, A. S., Jhund, P. S., Henderson, A., Lam, C. S. P., Senni, M., Shah, S. J., Voors, A. A., Zannad, F., Rossing, P., Ruilope, L. M., Anker, S. D., Pitt, B., Agarwal, R., Lay-Flurrie, J., Brinker, M., … Vaduganathan, M. (2026). Timing of cardiovascular and kidney benefits with finerenone in heart failure and chronic kidney disease with type 2 diabetes. Journal of the American College of Cardiology, 87(7), 788–792. doi:10.1016/j.jacc.2025.10.060.

• Pitt, B., Filippatos, G., Agarwal, R., Anker, S. D., Bakris, G. L., Rossing, P., Joseph, A., Kolkhof, P., Nowack, C., Schloemer, P., & Ruilope, L. M. (2021). Cardiovascular events with finerenone in kidney disease and type 2 diabetes. The New England Journal of Medicine, 385(24), 2252–2263. doi:10.1056/NEJMoa2110956.

• Rangaswami, J., Bhalla, V., Blair, J. E. A., Chang, T. I., Costa, S., Lentine, K. L., Lerma, E. V., Mezue, K., Molitch, M., Mullens, W., Ronco, C., Tang, W. H. W., & McCullough, P. A. (2019). Cardiorenal syndrome: Classification, pathophysiology, diagnosis, and treatment strategies: A scientific statement from the American Heart Association. Circulation, 139(16), e840–e878. doi:10.1161/CIR.0000000000000664.

• Solomon, S. D., McMurray, J. J. V., Vaduganathan, M., Claggett, B., Jhund, P. S., Desai, A. S., Henderson, A. D., Lam, C. S. P., Pitt, B., Senni, M., Shah, S. J., Voors, A. A., Zannad, F., Abidin, I. Z., Alcocer-Gamba, M. A., Atherton, J. J., Bauersachs, J., Chang-Sheng, M., Chiang, C.-E., … Viswanathan, P. (2024). Finerenone in heart failure with mildly reduced or preserved ejection fraction. The New England Journal of Medicine, 391(16), 1475–1485. doi:10.1056/NEJMoa2407107.

• Zannad, F., Ferreira, J. P., Pocock, S. J., Zeller, C., Anker, S. D., Butler, J., Filippatos, G., Hauske, S. J., Brueckmann, M., Pfarr, E., Schnee, J., Wanner, C., & Packer, M. (2021). Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: Insights from EMPEROR-Reduced. Circulation, 143(4), 310–321. doi:10.1161/CIRCULATIONAHA.120.051685.

• Zhao, B.-R., Hu, X.-R., Wang, W.-D., & Zhou, Y. (2025). Cardiorenal syndrome: Clinical diagnosis, molecular mechanisms and therapeutic strategies. Acta Pharmacologica Sinica, 46(6), 1539–1555. doi:10.1038/s41401-025-01476-z.

Publicado

2026-09-26

Cómo citar

[1]
Cristóbal Washington Franco Lucas, Trans., “Integrated Cardiorenal Risk in Multimorbidity: Emerging Biomarkers, Prognostic Stratification, and Contemporary Therapeutic Strategies”, IECCMEXICO, vol. 5, no. 2, Sep. 2026, doi: 10.64784/326.