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Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments
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Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 28 April 2026 | Viewed by 6739

Special Issue Editors

Dr. Pedro Caravaca-Pérez

E-Mail Website
Guest Editor
1. Heart Failure and Heart Transplant Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
2. Institut D́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Interests: heart failure; cardiorenal syndrome; heart transplantation
Dr. Jose Jesus Broseta

E-Mail Website
Guest Editor
Department of Nephrology and Renal Transplantation, Hospital Clínic Barcelona, 08036 Barcelona, Spain
Interests: dyalisis; heart failure; cardiorenal syndrome

Special Issue Information

Dear Colleagues,

Chronic kidney disease and heart failure are among the most prevalent comorbidities worldwide, significantly impacting patients' quality of life and survival. These conditions often coexist, creating a bidirectional and deleterious interplay referred to as cardiorenal syndrome (CRS), where one condition accelerates the development and progression of the other.

The diagnosis of CRS is associated with high rates of hospital readmissions, progressive clinical deterioration, and increased morbidity and mortality. This poses significant challenges for healthcare systems due to the high care burden and resource consumption. Despite recent therapeutic advancements, treatment implementation remains suboptimal, largely due to the lack of robust evidence and concerns about iatrogenic complications.

In this scenario, cardiorenal units have emerged as integrative, multidisciplinary models aimed at improving care delivery, education, and research for this complex patient population. Their implementation in recent years has demonstrated clear benefits, including reduced hospital readmissions, lower mortality rates, and more efficient resource utilization.

This Special Issue aims to advance the management of cardiorenal syndrome by promoting a multidisciplinary approach focused on developing new diagnostic tools to improve characterization and innovative therapeutic strategies to enhance patient outcomes.

Dr. Pedro Caravaca-Pérez
Dr. Jose Jesus Broseta
Guest Editors

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Keywords

  • heart failure
  • kidney disease
  • cardiorenal syndrome
  • diagnosis
  • treatment

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Published Papers (6 papers)

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Research

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14 pages, 1353 KB  
Article
Interaction Between Frailty and Renal Function in Patients with Heart Failure
by Ángela Rodríguez-Eguren, José Jesús Broseta, Lydia Izquierdo, Joan Llevadot-Sesmilo, Eduard Solé Gonzalez, María Ángeles Castel, Juan José Rodriguez, Elena Cuadrado-Payán, Diana Rodriguez-Espinosa, Elena Sandoval, Aleix Cases, Francisco Maduell, Ana García-Álvarez, Marta Farrero and Pedro Caravaca-Pérez
Life 2026, 16(1), 45; https://doi.org/10.3390/life16010045 - 26 Dec 2025
Viewed by 561
Abstract
Background. Frailty is highly prevalent among patients with heart failure (HF) and is associated with adverse clinical outcomes. Chronic kidney disease (CKD) frequently coexists with HF and may further increase risk. However, the clinical profile linking frailty and CKD remains insufficiently characterized. This [...] Read more.
Background. Frailty is highly prevalent among patients with heart failure (HF) and is associated with adverse clinical outcomes. Chronic kidney disease (CKD) frequently coexists with HF and may further increase risk. However, the clinical profile linking frailty and CKD remains insufficiently characterized. This study aimed to determine the prevalence and clinical correlates of frailty in outpatients with HF and to assess whether its prognostic significance varies across CKD severity. Methods. A prospective, observational cohort of HF outpatients was enrolled. Frailty was defined according to Fried’s phenotype (≥3 criteria). Factors associated with frailty were identified using logistic regression. The primary endpoint was a composite of all-cause mortality or HF hospitalization over one year. Cox proportional hazards models were used to evaluate associations between frailty and outcomes and to test its interaction with CKD. Results. A total of 459 HF outpatients (median age 75 [IQR 68–82] years; 72% men) were included. Frailty was present in 39.9% of patients and increased progressively with worsening renal function—from 14% in those with eGFR >60 to 38% in eGFR 30–60 and 48% in eGFR <30 mL/min/1.73 m2 (p < 0.001). In multivariate analysis, older age, prior stroke, higher CA125 levels, and lower eGFR were independently associated with frailty. Frail patients had a higher risk of all-cause death or HF hospitalization (adjusted HR 2.09; 95% CI 1.22–3.58; p = 0.007), with an amplified effect among those with advanced CKD (HR 5.02; 95% CI 2.46–10.22; p < 0.001). Conclusions. In HF outpatients, frailty is common and closely linked to renal dysfunction. Its coexistence with advanced CKD identifies a subgroup at the highest risk of adverse outcomes. Combined assessment of frailty and renal function may enhance prognostic precision and guide more individualized therapeutic strategies. Full article
(This article belongs to the Special Issue Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments)
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14 pages, 559 KB  
Article
Protocol Biopsies Reveal Progressive Arteriolar Thickening as a Predictor of Mortality in Kidney Transplant Recipients
by Diana Rodríguez-Espinosa, Evelyn Hermida, Agustín Leal-Cúpich, Adriana García, Ana Belén Larque, Elena Cuadrado-Payán, Elena Guillén-Olmos, Marina Moncada, Pedro Ventura-Aguiar, David Cucchiari, Nuria Esforzado, Ignacio Revuelta, Fritz Diekmann, José Vicente Torregrosa and José Jesús Broseta
Life 2025, 15(10), 1635; https://doi.org/10.3390/life15101635 - 20 Oct 2025
Viewed by 820
Abstract
Kidney transplant recipients remain at high risk of cardiovascular events and premature death. Whether chronic histological changes in protocol allograft biopsies provide prognostic information for patient outcomes beyond graft survival remains uncertain. In this prospective study of 458 kidney transplant recipients with biopsies [...] Read more.
Kidney transplant recipients remain at high risk of cardiovascular events and premature death. Whether chronic histological changes in protocol allograft biopsies provide prognostic information for patient outcomes beyond graft survival remains uncertain. In this prospective study of 458 kidney transplant recipients with biopsies performed at 3 and 12 months and followed up to 8 years, we assessed the association between vascular and interstitial lesions and major adverse cardiovascular events (MACEs) or all-cause mortality. Fifty-eight patients (12.7%) died and 49 (10.7%) experienced MACEs during follow-up. The most notable finding was that progression of hyaline arteriolar thickening (aah) between 3 and 12 months independently predicted all-cause mortality, even after adjustment for estimated glomerular filtration rate, diabetes, and previous cardiovascular disease. In addition, vascular fibrous intimal thickening at 12 months was also independently associated with mortality, while associations of baseline vascular or interstitial lesions were attenuated after full multivariable adjustment. These results suggest that progressive aah reflects an ongoing recipient-related vascular process rather than donor-derived injury. Monitoring this dynamic histological change in repeated biopsies performed for protocol or for cause may provide transplant nephrologists with an early signal of increased mortality risk. Full article
(This article belongs to the Special Issue Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments)
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13 pages, 933 KB  
Article
Relationship Between Subclinical Renal Damage and Maximum Rate of Blood Pressure Variation Assessed by Fourier Analysis of 24-h Blood Pressure Curve in Patients with Essential Hypertension
by Caterina Carollo, Alessandra Sorce, Maria Giovanna Vario, Emanuele Cirafici, Davide Bologna, Maria Elena Ciuppa, Salvatore Evola, Guseppe Mulè and Giulio Geraci
Life 2025, 15(7), 1149; https://doi.org/10.3390/life15071149 - 21 Jul 2025
Cited by 1 | Viewed by 1030
Abstract
Background: Blood pressure (BP) variability has been increasingly recognized as a predictor of cardiovascular and renal outcomes. However, the relevance of specific dynamic indices such as the maximum slope of systolic blood pressure (max SBP slope), derived through partial Fourier series modeling, in [...] Read more.
Background: Blood pressure (BP) variability has been increasingly recognized as a predictor of cardiovascular and renal outcomes. However, the relevance of specific dynamic indices such as the maximum slope of systolic blood pressure (max SBP slope), derived through partial Fourier series modeling, in relation to early renal damage remains underexplored. Methods: A total of 389 patients with essential hypertension were enrolled and stratified according to the estimated glomerular filtration rate (eGFR) ≥ or <90 mL/min/1.73 m2 and the presence of subclinical renal damage, defined by elevated urinary albumin excretion (AER) and/or reduced eGFR. All participants underwent clinical and biochemical evaluation, as well as 24-h ambulatory blood pressure monitoring (ABPM), including advanced hemodynamic analysis using Fourier-based modeling. Results: Patients with eGFR < 90 mL/min/1.73 m2 were older and exhibited higher waist circumference, uricemia, albuminuria, and systolic BP values, including the elevated max SBP slope (12.8 vs. 10.8 mmHg/h, p = 0.028). Subclinical renal damage was associated with older age; male sex; smoking; and higher levels of uricemia, clinical, and ambulatory BP, and the max SBP slope (14.2 vs. 10.7 mmHg/h, p = 0.007). The max SBP slope positively correlated with AER (r = 0.215, p < 0.001) and inversely with eGFR (r = −0.153, p = 0.002). In multivariate linear regression, the max SBP slope remained independently associated with AER (β = 0.220, p < 0.001), along with mean 24-h SBP, male sex, and the day–night SBP percentage dip. Logistic regression confirmed these associations with subclinical renal damage (max SBP slope OR: 1.536; 95% CI: 1.241–2.004; p = 0.001). Conclusions: The max SBP slope, a dynamic index of BP derived via Fourier analysis, is independently associated with markers of subclinical renal damage in hypertensive patients. This suggests that incorporating such advanced metrics into ABPM evaluation may improve early risk stratification and help identify individuals at greater risk of renal impairment, even in the absence of overt kidney disease. Full article
(This article belongs to the Special Issue Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments)
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Review

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20 pages, 974 KB  
Review
Acute Kidney Injury in Acute Heart Failure Revisited: Marker of Cardiorenal Disease Severity Rather Than Isolated Renal Injury
by Georgios Aletras, Maria Bachlitzanaki, Maria Stratinaki, Ioannis Petrakis, Yannis Pantazis, Emmanuel Foukarakis, Michalis Hamilos and Kostas Stylianou
Life 2026, 16(3), 486; https://doi.org/10.3390/life16030486 - 17 Mar 2026
Viewed by 104
Abstract
Background: Renal function deterioration during hospitalization for acute heart failure (AHF) is common and is traditionally classified as acute kidney injury (AKI) or worsening renal function (WRF) based on changes in serum creatinine (Cr). However, Cr-based definitions may inadequately reflect the complex [...] Read more.
Background: Renal function deterioration during hospitalization for acute heart failure (AHF) is common and is traditionally classified as acute kidney injury (AKI) or worsening renal function (WRF) based on changes in serum creatinine (Cr). However, Cr-based definitions may inadequately reflect the complex cardiorenal interactions occurring in AHF. Purpose: This narrative review summarizes and compares definitions of AKI and WRF used in AHF, evaluates their prognostic significance, and explores whether renal function deterioration should be interpreted as a marker of cardiorenal disease severity rather than isolated kidney injury. Methods: A narrative review of randomized trials, observational studies, post hoc analyses, and meta-analyses was conducted, focusing on Cr-based and nephrology-derived AKI definitions (RIFLE, AKIN, KDIGO), timing and baseline selection, congestion status, and the role of biomarkers and imaging in clinical interpretation. Results: The most widely used definition of WRF is an absolute increase in serum Cr ≥ 0.3 mg/dL. Multiple studies demonstrate that such changes frequently occur during effective decongestion and are not independently associated with adverse outcomes in the absence of residual congestion. In contrast, persistent congestion, impaired diuretic response, reduced renal reserve, and advanced cardiorenal comorbidity consistently predict worse prognosis. Nephrology-derived AKI definitions identify higher-risk patients but incompletely account for the hemodynamic and therapeutic context of AHF. Conclusions: In AHF, AKI and WRF often act as markers of underlying cardiorenal disease severity rather than direct indicators of irreversible kidney injury. Interpretation of renal function deterioration should be contextual, integrating congestion status, perfusion, renal reserve, and dynamic response to therapy. Achieving effective and complete decongestion remains the primary therapeutic objective in AHF, even in the presence of transient Cr increases. Full article
(This article belongs to the Special Issue Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments)
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29 pages, 1714 KB  
Review
Beyond Blood Pressure: Salt Sensitivity as a Cardiorenal Phenotype—A Narrative Review
by Maria Bachlitzanaki, Georgios Aletras, Eirini Bachlitzanaki, Nektaria Vasilaki, Charalampos Lydakis, Ioannis Petrakis, Emmanuel Foukarakis and Kostas Stylianou
Life 2026, 16(2), 247; https://doi.org/10.3390/life16020247 - 2 Feb 2026
Viewed by 863
Abstract
Background: Salt-sensitive blood pressure (SSBP) represents a prevalent yet underrecognized hypertensive phenotype, in which blood pressure (BP) and volume status are disproportionately influenced by dietary sodium intake. Beyond BP elevation alone, salt sensitivity reflects a convergence of renal sodium handling abnormalities, neurohormonal activation, [...] Read more.
Background: Salt-sensitive blood pressure (SSBP) represents a prevalent yet underrecognized hypertensive phenotype, in which blood pressure (BP) and volume status are disproportionately influenced by dietary sodium intake. Beyond BP elevation alone, salt sensitivity reflects a convergence of renal sodium handling abnormalities, neurohormonal activation, vascular dysfunction, and inflammatory pathways that link excessive sodium exposure to progressive kidney injury and adverse cardiac remodeling. Given its association with chronic kidney disease (CKD) and the association of heart failure with preserved ejection fraction (HFpEF), improved recognition of SSBP has direct clinical relevance. Objective: This narrative review aims to synthesize current mechanistic and clinical evidence on SSBP, focusing on pathophysiology, cardiorenal interactions, diagnostic challenges, and phenotype-guided therapeutic strategies with practical applicability. Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science from inception through January 2026. Experimental, translational, and clinical studies, along with relevant guideline documents, were integrated to provide conceptual and clinical interpretation rather than quantitative analysis. Key Findings: Impaired renal sodium excretion, intrarenal RAAS activation, sympathetic overactivity, endothelial dysfunction, and immune-mediated inflammation contribute to sodium retention, microvascular dysfunction, and fibrotic remodeling across the kidney–heart axis. These pathways are strongly supported by experimental and translational data, but direct interventional clinical validation remains limited for several mechanisms. Clinically, salt-sensitive individuals often exhibit non-dipping BP patterns, albuminuria, salt-induced edema, and a predisposition to HFpEF. Dynamic BP monitoring combined with targeted laboratory assessment improves identification of this phenotype and supports individualized management. Conclusions: Early recognition of SSBP enables targeted interventions beyond uniform sodium restriction. Phenotype-guided strategies integrating lifestyle modification, RAAS blockade, thiazide-like diuretics, mineralocorticoid receptor antagonists, and sodium-glucose co-transporters 2 inhibitors (SGLT2i) may improve cardiorenal outcomes. Emerging precision tools (e.g., wearable blood-pressure sensors, digital sodium tracking technologies, etc.) remain exploratory but may further refine individualized management. Full article
(This article belongs to the Special Issue Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments)
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35 pages, 1106 KB  
Review
Integrating Novel Biomarkers into Clinical Practice: A Practical Framework for Diagnosis and Management of Cardiorenal Syndrome
by Georgios Aletras, Maria Bachlitzanaki, Maria Stratinaki, Emmanuel Lamprogiannakis, Ioannis Petrakis, Emmanuel Foukarakis, Yannis Pantazis, Michael Hamilos and Kostas Stylianou
Life 2025, 15(10), 1540; https://doi.org/10.3390/life15101540 - 1 Oct 2025
Cited by 2 | Viewed by 2611
Abstract
Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and [...] Read more.
Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article
(This article belongs to the Special Issue Cardiorenal Disease: Pathogenesis, Diagnosis, and Treatments)
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