Fluid Overload in Cardiorenal Medicine: From Bench to Bedside Open Access

Congestion is not only a hallmark but a central driver of poor prognosis in both acute and chronic cardiorenal syndromes [1, 2]. Despite considerable advances in heart failure (HF) and nephrology care, managing volume status remains a major challenge due to the complex, bidirectional interaction between the heart and kidneys, the limitations of conventional assessment tools, and the growing heterogeneity of patient phenotypes. In this context, the collection “Fluid Overload in Cardiorenal Medicine: From Bench to Bedside” offers an important and timely contribution, bringing together diverse yet complementary perspectives on one of the most pressing and unresolved issues in contemporary cardiorenal medicine.

From a pathophysiological standpoint, congestion is not merely a symptom but a systemic process that mediates neurohormonal activation, renal hypoperfusion, and inflammatory responses, ultimately exacerbating both cardiac and renal dysfunction [1, 2]. Studies have consistently demonstrated that congestion is associated with increased mortality and recurrent hospitalizations, even in patients without overt clinical signs of volume overload [3, 4]. These observations underscore the urgent need for more precise diagnostic and prognostic tools.

The collection titled “Fluid Overload in Cardiorenal Medicine: From Bench to Bedside” brings together a compelling group of articles that explore the complex and central role of congestion in patients with coexisting heart and kidney dysfunction. Across a wide spectrum of clinical contexts – including acute and chronic HF, end-stage kidney disease on dialysis, and therapeutic decongestion strategies – these contributions collectively highlight the pressing need for improved assessment tools, personalized management approaches, and novel biomarkers to enable a more accurate evaluation of volume overload.

Several articles in this collection underscore the limitations of conventional volume status parameters and propose emerging markers that enhance our physiological understanding and contribute to a more nuanced phenotyping of congestion. For instance, Gayán Ordás et al. [5] explored the combined role of carbohydrate antigen 125 (CA125) and natriuretic peptides as complementary biomarkers for evaluating congestion in chronic HF. Their findings suggest that natriuretic peptides are more closely associated with intravascular congestion, whereas CA125 correlates with indicators of extravascular fluid accumulation [5]. In another study, Núñez-Marín et al. [6] examined urinary biomarkers of cell cycle arrest, identifying their potential utility in detecting patients at risk of diuretic resistance and early kidney function decline during the initial phase of hospitalization for acute HF.

From a prognostic perspective, recurrent hospitalizations due to congestion pose a major challenge in patients with cardiorenal syndrome [7]. This burden is particularly pronounced in individuals with coexisting diabetes and end-stage kidney disease on dialysis, where fluid management becomes especially complex. Phang et al. [8] addressed this clinical dilemma by identifying key predictors of recurrent fluid-related hospitalizations, paving the way for more targeted preventive strategies in this high-risk population.

From a therapeutic standpoint, this collection also highlights the evolving role of sodium-glucose cotransporter-2 inhibitors in cardiorenal medicine. Miñana et al. [9] demonstrated that dapagliflozin led to an early reduction in CA125 levels after discharge for acute HF, suggesting that this biomarker may serve as a useful tool for monitoring treatment response. In parallel, Tan et al. [10] analyzed real-world prescribing patterns of sodium-glucose cotransporter-2 inhibitors in patients with congestion and moderate-to-severe renal dysfunction. Their study revealed a persistent gap between clinical evidence and practice, particularly among older adults and those with advanced kidney disease.

Therapeutic options for patients with persistent congestion and diuretic resistance are re-examined with renewed focus. Villegas-Gutiérrez et al. [11] provided a comprehensive review of extracorporeal therapies and ultrafiltration strategies, advocating for a more proactive and individualized approach. Likewise, Belal and Kazory [12] offered an updated overview of ultrafiltration modalities – including peritoneal dialysis – highlighting their physiological rationale and clinical applicability in advanced HF management.

Beyond fluid removal strategies, this collection also addresses broader clinical implications. Yang et al. [13] proposed the Shock Index Creatinine as a novel prognostic tool for patients undergoing transcatheter aortic valve replacement, integrating hemodynamic stress with renal function metrics. In a separate conceptual review, Núñez-Marín et al. [14] linked cardiorenal syndrome with HF with preserved ejection fraction, positing that congestion serves both as a marker and mediator of risk in this increasingly recognized syndrome.

Although these contributions offer valuable insights, important challenges persist in congestion management. Residual congestion at discharge remains common, as highlighted by recent clinical trials such as ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload trial), where between 20% and 40% of patients still exhibited signs of congestion at discharge despite aggressive decongestive strategies [15]. Moreover, the absence of universally accepted diagnostic standards and the lack of randomized trials validating congestion-guided therapeutic approaches have hampered the integration of novel diagnostic tools into everyday clinical practice and formal clinical guidelines [16]. In addition, therapeutic strategies focused on intensified diuretic regimens have consistently failed to demonstrate improvements in clinical outcomes, such as mortality or hospital readmissions [15, 17‒23]. Altogether, these limitations underscore the pressing need for continued research, innovation, and refinement in the assessment and management of congestion. Moving forward, future investigations should prioritize precision medicine approaches, aiming to individualize congestion assessment and treatment to optimize outcomes in this complex and heterogeneous patient population.

In this context, the collection “Fluid Overload in Cardiorenal Medicine: From Bench to Bedside” represents a timely and important contribution. Its strength lies not only in the novelty of individual studies but also in the unifying message they convey: the need for a paradigm shift toward earlier detection, integrative assessment, and individualized management of congestion in cardiorenal patients.

By bringing together advances in biomarker development, imaging modalities, pharmacological innovation, and extracorporeal therapies, this collection offers a comprehensive view of the emerging tools that may reshape clinical practice. As our understanding of the complex heart-kidney interplay deepens, it becomes increasingly clear that precision strategies for diagnosing and treating congestion must take center stage in both research and clinical care. We hope you enjoy this collection, find the contributions valuable for the confident management of patients with cardiorenal syndrome, and – most importantly – are inspired to continue generating the evidence so greatly needed.