Cardiorenal Syndrome: Integrated Pathophysiology, Diagnostic Challenges, and Contemporary Therapeutic Approaches
DOI:
https://doi.org/10.64784/217Keywords:
Cardiorenal syndrome, heart failure, chronic kidney disease, nephrology, cardiology, internal medicine, venous congestion, neurohormonal activation, biomarkers, SGLT2 inhibitors, cardiovascular disease, renal dysfunction, inflammation, multidisciplinary care, cardiorenal interactionAbstract
Cardiorenal syndrome (CRS) represents a complex bidirectional interaction between the cardiovascular and renal systems in which dysfunction of one organ may induce or worsen dysfunction of the other. The increasing global prevalence of heart failure, chronic kidney disease, hypertension, obesity, and diabetes mellitus has significantly contributed to the growing clinical and epidemiological burden of CRS. This review aimed to analyze the principal pathophysiological mechanisms, diagnostic approaches, and contemporary therapeutic strategies associated with cardiorenal syndrome through an evidence-based analysis of current scientific literature. The study was developed as a narrative and analytical review using scientific evidence obtained from internationally recognized databases, including PubMed, Scopus, Web of Science, and high-impact journals in nephrology, cardiology, and internal medicine. The analysis focused on hemodynamic alterations, neurohormonal activation, venous congestion, inflammatory pathways, endothelial dysfunction, oxidative stress, diagnostic biomarkers, pharmacological therapies, and multidisciplinary management approaches. The reviewed evidence demonstrated that CRS is a multifactorial systemic condition involving complex interactions between cardiac and renal dysfunction. Venous congestion, activation of the renin–angiotensin–aldosterone system, sympathetic nervous system stimulation, chronic inflammation, and endothelial injury were identified as major contributors to disease progression. Biomarkers such as NT-proBNP, cystatin C, NGAL, and KIM-1 showed important diagnostic and prognostic value, although integrated clinical evaluation remains essential. Contemporary therapeutic strategies, particularly sodium-glucose cotransporter-2 inhibitors, demonstrated substantial cardiovascular and renal protective effects. Multidisciplinary care models were also associated with improved patient outcomes and optimization of long-term management. In conclusion, cardiorenal syndrome should be understood as a highly dynamic and multisystemic condition requiring integrated cardiovascular and renal assessment. Early diagnosis, evidence-based therapy, preventive medicine, and multidisciplinary collaboration remain fundamental for improving prognosis and reducing the global burden associated with CRS.
References
1. C. Ronco, P. A. McCullough, S. D. Anker, et al., “Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative,” Eur. Heart J., vol. 31, no. 6, pp. 703–711, 2010. doi: 10.1093/eurheartj/ehp507.
2. A. A. House, C. Ronco, P. A. McCullough, et al., “Definition and classification of Cardio-Renal Syndromes: workgroup statements from the 7th ADQI Consensus Conference,” Nephrol. Dial. Transplant., vol. 25, no. 5, pp. 1416–1420, 2010. doi: 10.1093/ndt/gfq136.
3. J. Rangaswami, D. L. Bhalla, J. E. Blair, et al., “Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies,” Circulation, vol. 139, no. 16, pp. e840–e878, 2019. doi: 10.1161/CIR.0000000000000664.
4. J. S. Chávez-Iñiguez, G. García-García, and C. Lombardi, “Cardiorenal syndrome: classification, pathophysiology, diagnosis and treatment,” Arch. Cardiol. Mex., vol. 92, no. 2, pp. 253–263, 2022. doi: 10.24875/ACM.20000356.
5. P. Hatamizadeh, A. Fonarow, M. Budoff, et al., “Cardiorenal syndrome: pathophysiology and potential targets for clinical management,” Nat. Rev. Nephrol., vol. 9, no. 2, pp. 99–111, 2013. doi: 10.1038/nrneph.2012.279.
6. U. Kumar, A. Wettersten, and R. J. Devarajan, “Cardiorenal syndrome: pathophysiology,” Cardiol. Clin., vol. 37, no. 3, pp. 251–265, 2019. doi: 10.1016/j.ccl.2019.04.001.
7. A. C. Mitsas, K. Tsioufis, C. Thomopoulos, et al., “Heart Failure and Cardiorenal Syndrome: A Narrative Review on Pathophysiology, Diagnostic and Therapeutic Regimens,” J. Clin. Med., vol. 11, no. 23, 2022. doi: 10.3390/jcm11237049.
8. S. Y. Lim, H. J. Jeong, and S. H. Lee, “Pathophysiology of Cardiorenal Syndrome and Use of Diuretics and Ultrafiltration as Volume Control,” Korean Circ. J., vol. 51, no. 9, pp. 713–728, 2021. doi: 10.4070/kcj.2021.0996.
9. R. Scagliola, M. Brunelli, and G. F. Mureddu, “Venous Congestion and Systemic Hypoperfusion in Cardiorenal Syndrome: Two Sides of the Same Coin,” J. Clin. Med., vol. 11, no. 6, 2022. doi: 10.3390/jcm11061641.
10. W. Mullens, Z. Abrahams, G. S. Francis, et al., “Importance of venous congestion for worsening of renal function in advanced decompensated heart failure,” J. Am. Coll. Cardiol., vol. 53, no. 7, pp. 589–596, 2009. doi: 10.1016/j.jacc.2008.05.068.
11. G. M. Felker, K. L. Lee, H. R. Bull, et al., “Diuretic Strategies in Patients with Acute Decompensated Heart Failure,” N. Engl. J. Med., vol. 364, no. 9, pp. 797–805, 2011. doi: 10.1056/NEJMoa1005419.
12. B. A. Bart, S. R. Goldsmith, K. L. Lee, et al., “Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome,” N. Engl. J. Med., vol. 367, no. 24, pp. 2296–2304, 2012. doi: 10.1056/NEJMoa1210357.
13. H. H. Chen, K. J. Anstrom, W. G. Givertz, et al., “Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial,” JAMA, vol. 310, no. 23, pp. 2533–2543, 2013. doi: 10.1001/jama.2013.282190.
14. P. A. Heidenreich, B. Bozkurt, D. Aguilar, et al., “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure,” Circulation, vol. 145, no. 18, pp. e895–e1032, 2022. doi: 10.1161/CIR.0000000000001063.
15. T. A. McDonagh, M. Metra, M. Adamo, et al., “2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure,” Eur. Heart J., vol. 44, no. 37, pp. 3627–3639, 2023. doi: 10.1093/eurheartj/ehad195.
16. Kidney Disease: Improving Global Outcomes CKD Work Group, “KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease,” Kidney Int., vol. 105, no. 4S, pp. S117–S314, 2024. doi: 10.1016/j.kint.2023.10.018.
17. Kidney Disease: Improving Global Outcomes Diabetes Work Group, “KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease,” Kidney Int., vol. 102, no. 5S, pp. S1–S127, 2022. doi: 10.1016/j.kint.2022.06.008.
18. J. J. V. McMurray, S. D. Solomon, S. E. Inzucchi, et al., “Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction,” N. Engl. J. Med., vol. 381, no. 21, pp. 1995–2008, 2019. doi: 10.1056/NEJMoa1911303.
19. H. J. L. Heerspink, B. V. Stefánsson, R. Correa-Rotter, et al., “Dapagliflozin in Patients with Chronic Kidney Disease,” N. Engl. J. Med., vol. 383, no. 15, pp. 1436–1446, 2020. doi: 10.1056/NEJMoa2024816.
20. The EMPA-KIDNEY Collaborative Group, “Empagliflozin in Patients with Chronic Kidney Disease,” N. Engl. J. Med., vol. 388, no. 2, pp. 117–127, 2023. doi: 10.1056/NEJMoa2204233.
