Kidney and Heart Cross-Talk-Interconnected Pathways and Clinical Challenges

Nicoletta Mancianti ^1* Marta Calatroni ² Giacomo Deferrari ³ Edoardo La Porta ⁴

• ¹ Department of Medical Science, Nephrology, Dialysis and Transplantation Unit, University Hospital of Siena, 53100 Siena, Italy., 53100, Italy
• ² Department of Biomedical Sciences, Humanitas University, Milan, Italy., Milan, Italy
• ³ Dipartimento di Cardionefrologia, Istituto Clinico Ligure di Alta Specialità, Rapallo, Italy
• ⁴ Giannina Gaslini Institute (IRCCS), Genoa, Liguria, Italy

Two organs, one fate: the intricate interplay between the heart and kidneys is not a simple equation, but a complex, bidirectional symphony in which dysfunction in one precipitates deterioration in the other. This reality highlights the strong connection between chronic kidney disease (CKD) and cardiovascular diseases (CVD). Patients with CKD face a cardiovascular risk that is significantly higher than that of the general population. CKD and CVD share common underlying mechanisms, including chronic inflammation, endothelial dysfunction, oxidative stress, metabolic dysregulation, and changes in gut microbiota. These factors contribute to the markedly increased cardiovascular risk in CKD patients. However, the management of this risk is often fragmented, indicating the need for a multidisciplinary and integrated approach.Our Research Topic has compiled key studies exploring these shared mechanisms, offering new perspectives on emerging biomarkers, therapeutic strategies, and physiological interactions. 2023) examined the impact of cardiac surgery-associated acute kidney injury on one-year major adverse kidney events, emphasizing the need for more effective preventive strategies in patients undergoing cardiovascular interventions (5).These studies underscore the crucial role of various pathophysiological factors in cardiorenal syndrome. Chronic inflammation and oxidative stress accelerate endothelial damage and disease progression, while mitochondrial dysfunction compromises energy metabolism, exacerbating both heart and kidney failure. Endothelial dysfunction and vascular calcification increase the risk of major cardiovascular events, whereas gut microbiota alterations contribute to systemic inflammation and organ damage. Managing pulmonary and systemic congestion in hemodialysis patients is essential to reduce mortality and improve quality of life.A growing body of research suggests that mitochondrial dysfunction plays a pivotal role in cardiorenal syndrome. The inability of mitochondria to maintain cellular energy production leads to increased oxidative stress, which further exacerbates endothelial damage and metabolic disturbances. These dysfunctions set off a cascade of events that contribute to both renal and cardiac deterioration. Additionally, alterations in calcium-phosphate metabolism have been linked to vascular calcification, a major risk factor for cardiovascular mortality in CKD patients.Despite advancements in research, managing cardiovascular risk in CKD patients remains challenging. The lack of an effective multidisciplinary approach and the underutilization of advanced biomarkers limit the efficacy of preventive strategies. Moreover, risk stratification often occurs only after cardiovascular symptoms appear, diminishing the impact of early intervention.Personalized therapies remain an ongoing challenge, as many cardiovascular treatments fail to account for the specificities of CKD.To improve clinical outcomes, an innovative approach is required, involving closer collaboration among specialists, extensive use of biomarkers to refine diagnosis, and new therapeutic strategies such as SGLT2 inhibitors and finerenone to mitigate cardiovascular risk in nephropathic patients.Optimizing dialysis and transplantation management, incorporating cardiovascular risk considerations, is equally essential to enhance prognosis. Furthermore, therapeutic approaches