Type 2 CRS is characterized by the development of renal dysfunction secondary to chronic cardiac disease. Despite its high morbidity and mortality, there is a lack of robust diagnostic tools and prognostic models to guide clinical management.

This multicenter retrospective study included patients diagnosed with CRS type 2 based on the 2019 American Heart Association definition. Data were collected from electronic medical records of three hospitals between January 2021 and December 2023. Advanced statistical methods, including receiver operating characteristic (ROC) curve analysis, univariate Kaplan-Meier (KM) analysis, and multivariable Cox proportional hazards regression, were utilized to develop a nomogram for predicting patient prognosis.

The study included 519 patients with CRS-2. Independent predictors of adverse outcomes included elevated serum creatinine and blood urea nitrogen (BUN) levels, decreased platelet count, elevated B-type natriuretic peptide (BNP), and decreased oxygen partial pressure (PaO2). These findings suggest that close monitoring of these markers is essential in clinical practice to identify patients at high risk of adverse events early on.

Our study provides evidence that serum creatinine, BUN, platelet count, BNP, and PaO2 are independent predictors of adverse outcomes in patients with Type 2 CRS.

Treatment of symptomatic/advanced heart failure (HF) in patients who also have chronic kidney disease (CKD) and type 2 diabetes (T2D) may include a steroidal mineralocorticoid receptor antagonist (MRA). However, patients with CKD and T2D who are at high risk of developing HF may benefit from taking the nonsteroidal MRA finerenone. Results from phase 3 placebo-controlled trials of finerenone in patients with CKD associated with T2D showed that finerenone (plus a renin-angiotensin-aldosterone system inhibitor) reduced the risk of new-onset HF, improved other HF outcomes, and caused a significant slowing of CKD progression. Those who work in cardiology need to be aware of the HF risk-reduction effects of finerenone in patients with CKD and T2D. In this review, we provide a rationale for finerenone use in cardiology based on the available finerenone clinical trial data and from the perspective of a cardiologist who prescribes finerenone to patients who have comorbid CKD and T2D.

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and is a risk factor for progression to end-stage kidney disease and cardiovascular morbidity and mortality. Despite pharmacologic treatment, residual risk of disease progression and adverse outcomes remains substantial. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) approved in the United States for use in patients with CKD associated with T2D. The present review focuses on finerenone use, including its pharmacologic basis, indication and eligibility, and practical aspects of incorporation into routine clinical practice (particularly primary care). Results from the two placebo-controlled phase 3 clinical trials of finerenone (plus maximum tolerated dose of a renin-angiotensin-aldosterone system inhibitor) in patients with CKD associated with T2D showed a significantly lower risk of CKD progression and cardiovascular events with finerenone versus placebo. These effects of finerenone were applicable across the broad spectrum of patient participants, including those with baseline comorbidities such as a history of heart failure or a history of atherosclerotic cardiovascular disease. We also compare finerenone to steroidal MRAs and discuss the relevance of ongoing and recently completed clinical trials of finerenone in other patient groups, which could expand finerenone use further to a broader spectrum of patients.

To assess the relationship between anti-inflammatory therapy and renal events risk in participants with cardiovascular risks or diagnosed cardiovascular disease (CVD).

Literature searches were carried out in PubMed, Embase, clinicaltrial.gov and the Cochrane Central Register of Controlled Trials. Randomised controlled trials that were published from January 1995 to July 2024, compared anti-inflammatory therapy and placebo in participants at cardiovascular risks or with diagnosed CVD and with reports of renal outcomes were included. The results were shown as risk ratio (RR) and 95% confidence interval (CI).

In comparison to placebo, therapies targeting inflammation did not exhibit a significant association with the risk of composite renal outcomes (worsening of renal function, death due to kidney disease and end-stage renal disease) (RR = 0.89, 95% CI 0.40 to 1.99, I2 = 0%). The risk of worsening of renal function (RR = 0.81, 95% CI 0.21 to 3.07, I2 = NA), end-stage renal disease (RR = 0.94, 95% CI 0.31 to 2.85, I2 = 0%), death due to kidney disease (RR = 3.00, 95% CI 0.12 to 73.56, I2 = NA), chronic kidney disease (RR = 1.77, 95% CI 0.74 to 4.23, I2 = 0%), chronic renal failure (RR = 1.70, 95% CI 0.56 to 5.15, I2 = 61%) and acute kidney injury (RR = 1.16, 95% CI 0.95 to 1.42, I2 = 0%) showed no significant difference between patients receiving anti-inflammatory therapy and placebo.

Current evidence did not indicate associations between anti-inflammatory therapies and adverse renal events risks in patients with cardiovascular risks or established CVD. Future researches are needed to explore the renal effects of anti-inflammatory therapy.

Mitochondria are essential organelles for cellular function and have become a broad field of study. In cardio-renal diseases, it has been established that mitochondrial dysfunction is a primary mechanism leading to these pathologies. Under stress, mitochondria can develop stress response mechanisms to maintain mitochondrial quality control (MQC) and functions. In contrast, the perturbation of these mechanisms has been associated with the pathogenesis of several diseases. Thus, targeting specific pathways within MQC could offer a therapeutic avenue for protecting mitochondrial integrity. However, the mechanisms related to MQC and mitochondrial stress signaling in the cardio-renal axis have been poorly explored. The primary limitations include the lack of reproducibility in the experimental models of cardio-renal disease, the incomplete knowledge of molecules that generate bidirectional damage, and the temporality of the study models. Therefore, we believe that integration of all of those limitations, along with recent advances in MQC mechanisms (i.e., mitophagy), stress signaling pathways (e.g., integrated stress response, mitochondrial unfolded protein response, and mitochondrial protein import), associated pharmacology, and targeted therapeutic approaches could reveal what the deregulation of these mechanisms is like and provide ideas for generating strategies that seek to avoid the progression of cardio-renal diseases.

Acute right ventricular failure (ARVF) is commonly seen in the intensive care unit and constitutes a significant clinical challenge, with associated high in-hospital mortality. Recently, the treatment of ARVF has significantly changed, with the progressive implementation of mechanical circulatory support devices that now represent important tools for clinicians in treating this condition. However, despite recent advancements, the optimal approach for ARVF remains elusive, and precise treatment algorithms and comprehensive management protocols are still lacking. In the present review, we explore the pathophysiology of ARVF, highlighting the different mechanisms that may lead to this clinical entity and emphasizing the left and right heart's complex interplay. We analyze the different therapeutic options that are now available for short- and long-term management of ARVF, with a particular focus on the advantages and disadvantages of the mechanical circulatory support devices actually used. Furthermore, we propose future directions in the field and a possible flowchart for the treatment of this condition.

Late kidney allograft loss occurs through one of two mechanisms: ( 1 ) deterioration of kidney function leading to retransplantation or dialysis (death-censored graft loss) and ( 2 ) premature death with a normally functioning transplant (death with graft function)-each accounting for approximately 50% of late kidney graft losses. Late death-censored graft loss typically results from a combination of immune and nonimmune events leading to common nonspecific end points ( e.g ., tubular atrophy, interstitial fibrosis, and glomerulosclerosis). Conversely, leading causes of death with graft function typically include cardiovascular events, malignancy, and infection. With an improved understanding of the multiple mechanism by which late graft dysfunction develops, there is an opportunity to identify patients at greatest risk and institute novel strategies to quell the process. Newer cardiometabolic agents with proven benefit in the general population have not been well-studied in kidney transplant recipients. However, in addition to their potential benefits in reducing cardiovascular, infectious, and malignancy end points (thus minimizing death with graft function risk), many novel agents may have additional anti-inflammatory and/or antifibrotic benefit (minimizing death-censored graft loss risk) in the kidney transplant population. In this review, we summarize existing literature regarding major causes of death-censored graft loss and death with graft function and discuss the potential roles of new cardiorenal metabolic agents including sodium-glucose cotransport 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, glucagon-like peptide 1 receptor agonists, and dual endothelin and angiotensin receptor antagonists in the kidney transplant population, including potential mechanisms to improve death with graft function and death-censored graft loss outcomes.

Positron emission tomography (PET) imaging is widely used to detect focal lesions or diseases and to study metabolic abnormalities between organs. However, analyzing organ correlations alone does not fully capture the characteristics of the metabolic network. Our work proposes a graph-based analysis method for quantifying the topological properties of the network, both globally and at the nodal level, to detect systemic or single-organ metabolic abnormalities caused by diseases such as lung cancer.

We used whole-body 18F-fluorodeoxyglucose (18F-FDG) standardized uptake value (SUV) images from 32 lung cancer patients and 20 healthy controls to construct two-organ glucose metabolism correlation networks at the population level. We calculated five global measures and three nodal centralities for these networks to explore the small-world, rich-club and modular organization in the metabolic network. Additionally, we analyzed the preference for connections significantly affected by lung cancer by dividing organs according to system level and spatial location.

In lung cancer patients, functional segregation in metabolic networks increased (increasedC p ${{C}_p}$ ,E loc ${{E}_{{\mathrm{loc}}}}$ , and Q $Q$ , t < 0), whereas functional integration decreased (increasedL p ${{L}_p}$ , t < 0, and decreasedE glob ${{E}_{{\mathrm{glob}}}}$ , t > 0), indicating more localized and dispersed metabolic activities. At the nodal level, certain organs, such as the pancreas, liver, heart, and right kidney, were no longer hubs in lung cancer patients (decreased nodal centralities, t > 0), whereas the left adrenal gland, left kidney, and left lung showed significantly increased centralities (increased nodal centralities, t < 0). This change suggests compensatory effects between organs. Connections between the nervous and urinary systems, as well as between the upper and middle organs, were more strongly affected by lung cancer (p < 0.05).

Our study demonstrates the utility of graph theory in analyzing PET imaging data to uncover metabolic network abnormalities. We identified significant topological changes and shifts in nodal roles in lung cancer patients, indicating a shift toward localized and segregated metabolic activities. These findings emphasize the need to consider systemic interactions and specific organ connections affected by disease. The impact on connections between the nervous and urinary systems and between the upper and middle regions underscores the modular nature of organ interactions, offering insights into disease mechanisms and potential therapeutic targets.

Congestion is a key clinical feature of heart failure (HF), contributing to hospitalizations, disease progression, and poor outcomes. While traditionally considered a hemodynamic issue, congestion is now recognized as a systemic process affecting multiple organs. Renal dysfunction arises from impaired perfusion and sodium retention, leading to maladaptive left ventricular remodeling. Hepatic congestion contributes to cholestatic liver injury, while metabolic disturbances drive anemia, muscle wasting, and systemic inflammation. Additionally, congestion disrupts the intestinal barrier and immune function, exacerbating HF progression. Given its widespread impact, effective congestion management requires a shift from a cardiovascular-centered approach to a comprehensive, multidisciplinary strategy. Targeted decongestive therapy, metabolic and nutritional optimization, and immune modulation are crucial in mitigating congestion-related organ dysfunction. Early recognition and intervention are essential to slow disease progression, preserve functional capacity, and improve survival. Addressing HF congestion through personalized, evidence-based strategies is vital for optimizing long-term care and advancing treatment paradigms.

Cardiac and kidney diseases are intimately linked through numerous pathophysiological pathways, frequently exerting reciprocal influences on one another. This interconnection often culminates in heightened morbidity and mortality rates within the clinical spectrum of cardiorenal syndrome (CRS). CRS is categorized into five types based on the primary organ involved and the chronicity of the condition. Each type of CRS encompasses a complex array of pathophysiological mechanisms. In recent years, the field of microRNAs (miRNAs) has risen to prominence, playing a crucial role in the pathogenesis of a multitude of diseases. By uncovering novel therapeutic targets through the study of miRNAs that influence the expression of the CRS genes, the prognostic outcomes for patients could be significantly improved. This article provides a comprehensive review, examining the pathophysiological underpinnings of CRS, miRNAs alterations and their associated mechanisms in various forms of CRS, as well as the potential of miRNAs in precision medicine and the use of miRNAs for the diagnosis of the disease.

The role of loop diuretics in patients with acute kidney injury (AKI) is controversial. This study examined the association between the use of loop diuretics and prognosis in critically ill patients with AKI.

This study used data from the medical information mart for the intensive care IV database. Adult critically ill patients with AKI were included in the analysis. Patients were partitioned into two groups based on their use of loop diuretics in the ICU, and potentially confounding variables between the two groups were balanced using propensity score matching (PSM). We used time-dependent Cox proportional hazards regression, logistic regression, and Hodges-Lehman estimator to assess the impact of loop diuretics on all-cause mortality, renal replacement therapy (RRT) use, and the length of hospital stay, respectively.

This study included a cohort of 19,671 patients. After PSM, both groups consisted of 6200 patients. The use of loop diuretics was associated with a lower risk of in-hospital mortality (HR, 0.672; 95% CI 0.597-0.757; P < 0.001), lower in-ICU mortality (HR, 0.375; 95% CI 0.315-0.446; P < 0.001), and lower odds of in-hospital RRT (OR, 0.472; 95% CI 0.400-0.555; P < 0.001). A sensitivity analysis using the original cohort (HR, 0.624; 95% CI 0.561-0.693; P < 0.001) and weighted cohort (HR, 0.654; 95% CI 0.582-0.736; P < 0.001) also demonstrated lower in-hospital all-cause mortality.

The use of loop diuretics is associated with a substantial reduction in mortality among critically ill patients with AKI.

High-intensity interval training (HIIT) has been recognized as an effective form of short-duration exercise. The purpose of this study was to assess whether HIIT could reduce renal injury induced by myocardial ischemia-reperfusion (MIR) in rats.

Male Sprague-Dawley rats were randomly assigned to the Sham (SHAM), coronary artery occlusion (CAO), HIIT, and ischemic precondition (IPC) groups. Rats underwent 40 minutes of left anterior descending CAO under anesthesia, followed by 3 hours of reperfusion, to induce MIR. Postsurgery, rats were sacrificed, and their blood, heart, and kidney tissues were examined. The HIIT group underwent 4 weeks of HIIT training before surgery.

HIIT intervention significantly reduced renal injury after MIR and the concentrations of blood urea nitrogen (BUN) and creatinine (CRE) in the serum. Moreover, proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, were significantly decreased, while the anti-inflammatory cytokine IL-10 was significantly increased in the serum. Additionally, HIIT intervention suppressed the expression of FoxO1, Bax/Bcl-2 ratio, TNF-α, and cleaved-caspase-3/caspase-3 ratio in kidney tissues, ultimately reducing renal cell apoptosis.

This study is the first to demonstrate that HIIT has effects similar to IPC, significantly reducing renal injury after MIR. HIIT regulates the production of proinflammatory and anti-inflammatory cytokines and inhibits renal cell apoptosis, thereby reducing the occurrence of cardiorenal syndrome.

The plasma uric acid/albumin ratio (UAR) has emerged as a novel inflammatory biomarker for predicting the development of acute kidney injury (AKI) following percutaneous coronary intervention. However, the potential of the UAR to serve as a predictive marker for AKI in patients undergoing isolated tricuspid valve (TV) surgery remains unknown. This study aimed to explore the association between the UAR and AKI and to assess whether the UAR can predict AKI in these patients.

We conducted a retrospective analysis of patients who underwent isolated TV surgery between January 2018 and June 2019. The patients were divided into three groups based on the tertiles of the UAR. We utilized multivariate logistic regression and restricted cubic spline analysis to examine the association between the UAR and AKI. Additionally, we used the receiver operating characteristic (ROC) curve analysis to assess the predictive accuracy of the UAR for AKI.

A total of 224 patients were enrolled in this study, of whom 41 developed AKI. The incidence of AKI across the three UAR tertiles was 3.8%, 22.2%, and 29.7%, with a significant difference between the group (p < 0.001). In the multivariate analysis, UAR ≥8.5 was associated with a 7-fold increased risk of AKI (odds ratio (OR): 7.73, 95% confidence interval (CI): 1.61-37.14), while a UAR ≥10.8 was a linked to a 9-fold increased risk (OR: 9.34, 95% CI: 1.96-44.60). The restricted cubic spline model showed a linear association between the UAR and AKI development. The area under the curve (AUC) value for the UAR was 0.713 (95% CI: 0.633-0.793; p < 0.001) with a cutoff value of 8.89.

An increased UAR was significantly associated with a higher risk of AKI in patients undergoing isolated TV surgery; however, while the UAR could serve as a marker to predict AKI, it was not superior to uric acid alone.

Chronic kidney disease (CKD) is on the rise, and over 50% of patients die from cardiac causes. Patients develop heart failure due to unelucidated reno-cardiac interactions, termed type 4 cardiorenal syndrome (CRS4). The aim of this study is to establish and characterize a reliable model of CRS4 in swine with marked cardiac diastolic dysfunction. Yorkshire pigs (19.9 ± 1.7 kg, 4 females and 5 males) underwent staged renal artery embolization using autologous clot. Echocardiogram, aortic pressure (AoP), renal angiogram, and blood samples were assessed monthly. At 4 mo, animals were euthanized after measuring glomerular filtration rate (GFR) and left ventricular (LV) pressure-volume parameters. Heart and kidneys were collected for postmortem analyses. Size-matched swine (n = 5; 43.7 ± 9.8 kg) served as controls. After three dose-titrated renal embolization, serum creatinine (SCr) and AoP increased by wk 10. At 4 mo, SCr (2.03 ± 0.45 vs. 1.34 ± 0.17 mg/dL, P = 0.013) and AoP (158 ± 16 vs. 121 ± 8 mmHg, P = 0.001) were higher, and GFR was lower (12 ± 3 vs. 131 ± 7 mL/min, P < 0.001) than size-matched controls. Although the LV ejection fraction was similar, the slope of the end-diastolic pressure-volume relationship was steeper in pigs after renal embolization (0.36 ± 0.09 vs. 0.17 ± 0.06, P = 0.003), indicating increased LV stiffness. LV mass index (2.73 ± 0.19 vs. 2.50 ± 0.13 g/kg, P = 0.043) and wall-thickness (11.4 ± 0.8 vs. 8.9 ± 1.2 mm, P = 0.003) increased. These were accompanied by histologically increased fibrosis, cardiomyocyte hypertrophy, and vascular rarefaction. Repeat titrated renal embolization resulted in a model that exhibits advanced CKD and cardiac abnormalities consistent with CRS4.NEW & NOTEWORTHY Cardiac pathological changes consistent with heart failure with preserved ejection fraction can be induced in a large animal model by serial and titrated renal embolization of kidneys with autologous clot, leading to severe renal dysfunction and impaired cardiac diastolic function.

Cardiorenal syndrome (CRS) is a complex clinical disorder characterized by the interplay between heart and kidney dysfunction. This condition is exacerbated by comorbidities such as diabetes mellitus, which contribute to glucose-mediated oxidative stress, further complicating the management of CRS. The management of CRS has evolved with the discovery of sodium-glucose-cotransporter-2 (SGLT2) inhibitors, which have been established as effective agents in reducing hyperglycemia and demonstrated cardiorenal protective effects. Concurrently, intermittent fasting has gained attention as an intervention without pharmacological treatment for its metabolic benefits, including improved glucose metabolism and insulin regulation and sensitivity, both with a potential reduction in oxidative stress. This review provides a summary of current findings on the roles of SGLT2 inhibitors and intermittent fasting in managing CRS, with a particular focus on glucose-mediated oxidative stress. We evaluate the mechanisms by which these interventions exert their effects, identify gaps in current research, and offer recommendations for future studies. While both SGLT2 inhibitors and intermittent fasting demonstrate potential in managing CRS, more research is needed to elucidate their long-term efficacy, safety, and potential synergistic effects.

As the engine that maintains blood circulation, the heart is also an endocrine organ that regulates the function of distant target organs by secreting a series of cardiokines. As endocrine factors, cardiokines play an indispensable role in maintaining the homeostasis of the heart and other organs. Here, we summarize some of the cardiokines that have been defined thus far and explore their roles in heart and kidney diseases. Finally, we propose that cardiokines may be a potential therapeutic target for kidney diseases.

Cardiorenal syndrome (CRS) is an interdependent dysfunction of the heart and kidneys, where failure in one organ precipitates failure in the other. The pathophysiology involves sustained renin-angiotensin-aldosterone-system (RAAS) activation, mitochondrial dysfunction, inflammation, fibrosis, oxidative stress and tissue remodeling, culminating in organ dysfunction. Existing therapies targeting the RAAS, diuretics and other agents have limitations, including diuretic resistance and compensatory sodium reabsorption. Therefore, there is a pressing need for novel druggable targets involved in CRS pathogenesis. This review addresses the challenges of existing treatments and emphasizes the importance of discovering new therapeutic targets. It highlights emerging targets such as Klotho, sex-determining region Y box 9 (SOX9), receptor-interacting protein kinase 3 (RIPK3), β-amino-isobutyric acid (BAIBA), thrombospondin-1 (TSP-1), among others, with their potential roles in CRS.

The relationship between cardiac and renal function is complicated. The impact of percutaneous coronary intervention (PCI) on renal function in patients with coronary artery disease is still unclear. The current study sought to assess renal function change, including the time course of renal function, after elective PCI in patients with improved renal function (IRF) and to identify renal function predictors of major adverse cardiovascular events (MACE). We examined data from 1572 coronary heart disease patients who had coronary angiography (CAG) or PCI in this retrospective cohort study. Patients receiving elective PCI (n=1240) and CAG (n=332) between January 2013 and December 2018 were included. Pre-PCI and procedural variables associated with post-PCI estimated glomerular filtration rate (eGFR), change in renal function after post-PCI follow-up, and post-PCI eGFR association with MACE were investigated. Following the procedure, 88.7% of PCI group patients had unchanged IRF. The treatment of PCI was found to independently correlate with IRF following CAG in an analysis of patients undergoing PCI [odds ratio 4.561 (95% confidence interval: 2.556-8.139); p<0.001]. The area under the receiver operating characteristic curve is 0.763 (model with the treatment of PCI). IRF and stable renal function were both associated with a lower risk of a MACE.

Chronic kidney disease (CKD) is a multifactorial disease affecting more than 13.4% of the world's population and is a growing public health problem. It is silent in its early stages and leads to irreversible kidney damage as the disease progresses. A key factor in this progression is the bidirectional relationship between CKD and gut dysbiosis, which creates an imbalance that promotes the accumulation of uremic toxins (UTs), contributing to renal fibrosis, endothelial dysfunction, and decreased glomerular filtration rate. In addition, CKD itself exacerbates gut dysbiosis by altering the composition of the gut microbiota (GM) and promoting the growth of pathogenic microorganisms. Therefore, it is crucial to explore new therapeutic strategies, and the use of probiotics and synbiotics has shown promise in modulating the GM. Numerous preclinical studies have shown that the use of probiotics in CKD has a beneficial effect on the kidney by reducing UTs, apoptosis, inflammation, and oxidative stress. Probiotic treatment has also been associated with restoration of intestinal integrity, modulation of microbial composition and diversity, and increased production of short-chain fatty acids (SCFAs). These positive results have also been observed in patients at different stages of CKD, where the use of probiotics and/or synbiotics was able to improve creatinine levels and uremic parameters and alleviate abdominal discomfort, in addition to modulating GM and reducing serum endotoxin levels. Although recent studies have explored the benefits of probiotics in the treatment of CKD, further research is needed to determine their long-term efficacy and clinical relevance. This review focuses on the factors driving gut dysbiosis in CKD, its role in disease progression, and the potential of probiotics as a therapeutic strategy.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as "cardiorenal syndrome," where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure-chronic heart failure (CRF-CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a "two-step surgical method"), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF-CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF-CHF groups showed significant increases in LVEDP and LVW/BW (P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Compared to the CRF and CHF groups, the CRF-CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Rats with CRF-CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

Polycystic ovarian syndrome (PCOS) has been associated with cardiovascular risks and comorbid pathologies, particularly cardiorenal disorder. Short-chain fatty acids (SCFAs), especially butyrate, are essential fatty acids that regulate metabolic health and ameliorate granulosa inflammation in PCOS. However, the effect of butyrate on cardiorenal damage associated with PCOS is unknown. This study investigated the impact of SCFA and butyrate on cardiorenal abnormalities in PCOS rat model and the probable involvement of paraoxonase-1 (PON-1).

Eight-week-old female Wistar rats were allotted into three groups, n = 5, namely control (CTL), PCOS (LEZ), and LEZ + BUT. Induction of PCOS with letrozole (1 mg/kg) lasted for 21 days, while treatment with butyrate (200 mg/kg) commenced after the induction and lasted for 6 weeks uninterruptedly.

PCOS rats showed hyperandrogenism, multiple ovarian cysts, disrupted metabolic indices (fasting insulin and homeostatic model of insulin resistance), and increased (p < 0.05) plasma troponin T, urea, and creatinine, as well as increased cardiac/renal stroma cell-derived factor-1/caspase-6, malondialdehyde/nuclear factor-kappaB, transforming growth factor-β1, and renal ϒ-glutamyl transferase, while a significant decrease (p < 0.05) in systemic nitric oxide/endothelial nitric oxide synthase and cardiac/renal hypoxia-inducible factor-1α and nuclear factor erythroid 2-related factor 2, which were accompanied with a decreased level of PON-1. These systemic and cardiorenal derangements were reversed by butyrate administration.

The results demonstrate the therapeutic benefits of SCFAs, butyrate, against cardiorenometabolic disorder in a model of PCOS. This beneficial effect is accompanied by an elevated level of PON-1. The present data possibly provides a preclinical relevance for the management of cardiorenal syndrome in PCOS.

There is a lack of diagnostic non-invasive imaging technology for assessing the early structural and functional changes of the kidney in type 2 cardiorenal (CRS) patients. This study aims to explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for clinical application in type 2 CRS patients, to provide imaging markers for the assessment of kidney damage.

This is a retrospective observational clinical study conducted in Nanjing, China. The clinical characteristics, including age, gender, medical history, laboratory results, and ultrasound and magnetic resonance imaging results were collected from the electronic medical record. Thirty-one patients with type 2 CRS, 20 patients with chronic heart failure (HF) and 20 healthy controls were enrolled and divided into type 2 CRS, HF and control groups. All the participants underwent magnetic resonance imaging (MRI) scanning. The apparent diffusion coefficient (ADC) value and IVIM-DWI parameters including true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were obtained. The correlation between estimated glomerular filtration rate (eGFR), renal size and imaging parameters was evaluated by Spearman correlation analysis.

ADC and D of the renal cortex in patients with type 2 CRS were lower than those in the healthy control group. ADC and f in the HF group were lower than those in the control group. D was positively correlated with the length (r = 0.3752, P = 0.0013) and transverse diameter (r = 0.3258, P = 0.0056) of the kidney. ADC (r = 0.2964, P = 0.0121) and D (r = 0.3051, P = 0.0097) were positively correlated with eGFR. Renal cortical ADC and D values could distinguish type 2 CRS patients from the healthy controls with area under the curve (AUC) of 0.723 and 0.706, respectively.

The ADC and D values were not only correlated with renal function, but also had lower levels in type 2 CRS. The IVIM-DWI parameter D was also related to kidney size, but further research is needed to determine whether it can be used as a novel imaging marker for type 2 CRS.

Cardiovascular diseases (CVD), chronic kidney disease (CKD), and lipids are positively correlated with the presence of depressive symptoms. However, investigation into the complex link that exists between cardiorenal syndrome (CRS) and lipid indices and depression remains scarce.

This study analyzed data from 11, 729 adults in the National Health and Nutritional Examination Surveys from 2005 to 2018. Weighted regression analysis was employed to examine the relationships between CRS and depression, CRS and the Patient Health Questionnaire-9 score, and lipid indices with depression. The restricted cubic spline analysis was used to determine whether there is a linear association between lipid indices and depression. Smooth curve fitting was employed to illustrate the relationship between lipids, depression, and cardiorenal diseases. Subgroup and sensitivity analyses were also conducted to enhance the stability of the results. Finally, we applied mediation analysis to explore whether the Atherogenic Index of Plasma (AIP), triglyceride glucose (TyG) index, and remnant cholesterol (RC) mediate the association between CRS and depression.

After applying propensity score matching (PSM), 1,509 adults remained in the study. After PSM, more remarkable results were rendered that CRS was associated with depression compared with non-CRS (OR: 1. 240, 95% CI: 1. 237 ~ 1. 243), only-CVD (OR: 0. 646, 95% CI: 0. 644 ~ 0. 649), and only-CKD (OR: 1.432, 95% CI: 1.428 ~ 1.437) in a fully corrected model. Smooth curve fitting shows that the intersection point of the lines of CRS and non-CRS occurs at a higher value on the horizontal axis than the intersection point of the lines representing CVD and non-CVD. In the fully corrected model, AIP, TyG, and RC did not independently mediate the association between CRS and depression.

There was a significant association between CRS and depression and a linear relationship between AIP, TyG, and RC and depression. However, the above lipid indicators did not mediate the association between CRS and depression.

Myocardial injury is common in end-stage renal disease (ESRD) patients, but the presence and severity of myocardial injury in different left ventricular (LV) phenotypes were still not fully explored.

To evaluate myocardial tissue characteristics and deformation in ESRD patients on peritoneal dialysis separated into normal geometry, concentric remodeling, concentric left ventricular hypertrophy (LVH) and eccentric LVH patterns by multiparametric cardiac MRI.

Prospective.

A total of 142 subjects, including 102 on peritoneal dialysis (69 males) and 40 healthy controls (27 males).

At 3.0 T, cine sequence, T1 mapping and T2 mapping.

LV mass index and LV remodeling index were used to create four subgroups with normal geometry, concentric remodeling, concentric LVH, and eccentric LVH. LV function, strain and strain rate, myocardial native T1 and T2 were measured.

Descriptive statistics, analysis of variance and analysis of covariance, Pearson/Spearman correlation, stepwise regression, and intraclass correlation coefficient. P-value <0.05 was considered statistically significant.

Even in normal geometry, LV strain parameters still diminished compared with the controls (global radial strain: 30.5 ± 7.7% vs. 37.1 ± 7.9%; global circumferential strain: -18.2 ± 2.6% vs. -20.6 ± 2.2%; global longitudinal strain: -13.3 ± 2.5% vs. -16.0 ± 2.8%). Eccentric LVH had significantly lower global circumferential systolic strain rate than concentric LVH (-0.82 ± 0.21%/-second vs. -0.96 ± 0.20%/-second). Compared with the controls, the four subgroups all revealed elevated native T1 and T2, especially in eccentric LVH, while concentric remodeling had the least changes including native T1, T2, and LV ejection fraction. After adjusting for covariates, there was no statistically significant difference in T2 between the four subgroups (P = 0.359).

Eccentric LVH is associated with the most pronounced evidence of myocardial tissue characteristics and function impairment, while as a benign remodeling, the concentric remodeling subgroup had the least increase in native T1. This study further confirms that native T1 and strain indicators can reflect the severity of myocardial injury in ESRD, providing better histological and functional basis for future grouping treatments.

1 TECHNICAL EFFICACY: Stage 3.

The objective of this study is to develop and validate an effective prognostic nomogram for predicting the short-term survival rate of patients with acute heart failure (AHF) complicated by acute kidney injury (AKI) who are admitted to the intensive care unit (ICU).

We conducted an analysis of data from patients of AHF with AKI spanning the period from 2008 to 2019, utilizing the MIMIC-IV database. Patients were randomly divided into training and validation sets. The training set employed the least absolute shrinkage and selection operator regression model to identify predictors of AKI. Subsequently, a dynamic nomogram was constructed using multivariate Cox regression analysis within the training set and was subsequently validated using the validation set. The nomogram's predictive accuracy, calibration, and clinical utility were evaluated through the concordance index (C-index), calibration plots, and decision curve analysis (DCA).

A total of 978 AHF patients with AKI were analyzed. Multivariate analysis identified serum creatinine, race, age, use of human albumin, use of vasoactive drug, and hemoglobin as independent predictors significantly influencing the short-term prognosis of AHF patients with AKI upon ICU admission. The C-index for the training and validation sets were 0.81 (95%CI: 0.74-0.87) and 0.80 (95 % CI: 0.67-0.92), respectively. The calibration plot of the nomogram demonstrated a close alignment between predicted and observed probabilities. Furthermore, the DCA confirmed the clinical utility of the nomogram.

This study presents a dynamic nomogram that incorporates clinical risk factors and can be conveniently utilized to predict short-term prognosis for AHF patients with AKI upon ICU admission.

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein-protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram's area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD.

Cardiorenal syndrome (CRS) is a complex condition characterized by the interplay of immune imbalance and inflammation. The C-reactive protein-Albumin-lymphocyte (CALLY) CALLY index serves as a new immune-nutritional scoring system, but its predictive value for CRS remains to be established.

In this study, we analyzed data from 27,978 participants in National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The CALLY index was calculated as the ratio of albumin to lymphocyte, divided by C-reactive protein (CRP) multiplied by 104. CRS was defined by the coexistence of cardiovascular disease and chronic kidney disease (eGFR <60 mL/min/1.73 m2). Multivariate weighted logistic regression models were employed to determine the odds ratio and 95 % confidence interval for the association between the CALLY index and CRS. Receiver operating characteristic (ROC) curves and restricted cubic spline (RCS) curves were used to assess the predictive efficacy and nonlinear relationship, respectively.

The prevalence of CRS in the study population was 1.22 %. Our findings revealed a significant inverse relationship between the CALLY index and CRS risk, with lower CALLY index values being associated with a higher likelihood of CRS (OR = 0.95, 95 % CI = 0.94-0.96, P < 0.001). Participants in higher quartiles of the CALLY index showed a progressively reduced risk of CRS (P for trend <0.001). Moreover, the CALLY index demonstrated superior predictive performance compared to other inflammatory indicators, such as systemic immune-inflammation index (SII), neutrophil/high-density lipoprotein ratio (NHR), lymphocyte/high-density lipoprotein ratio (LHR), monocyte/high-density lipoprotein ratio (MHR), and platelet/high-density lipoprotein ratio (PHR) (AUC = 0.672, 95 % CI = 0.643-0.701).

This study underscores the significant negative correlation between the CALLY index and the risk of cardiorenal syndrome. The CALLY index emerges as a robust and independent predictor of CRS, outperforming traditional inflammatory markers. This finding highlights the potential utility of the CALLY index as a clinical tool for identifying individuals at risk for CRS.

Sacubitril-valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction (HFrEF). However, its long-term protective effects on cardiac function with concurrent acute kidney injury (AKI) remain unclear. This study investigated the recovery of cardiac function relative to kidney function decline.

A total of 512 patients with HFrEF who started sacubitril-valsartan or valsartan treatment were enrolled in cohort 1. Additionally, patients who experienced AKI and underwent follow-up transthoracic echocardiography were enrolled in cohort 2. In cohort 1, short- and long-term kidney outcomes were analyzed. For cohort 2, changes in cardiac function in relation to changes in kidney function after drug initiation were analyzed.

The mean age of the patients was 68.3 ± 15.1 years, and 57.4% of the patients were male. AKI occurred in 15.9% of the sacubitril-valsartan group and 12.5% of the valsartan group. After AKI, 78.4% of patients in the sacubitril-valsartan group and 71.4% of those in the valsartan group underwent recovery. Furthermore, cardiovascular outcomes in patients who developed AKI after drug initiation were analyzed in cohort 2. The sacubitril-valsartan group showed a greater improvement in cardiac function compared with the valsartan group (12.4% ± 15.4% vs. 1.4% ± 5.7%, p = 0.046). The ratio of deltas of cardiac and kidney function in the sacubitril-valsartan and valsartan groups were -1.76 ± 2.58 and -0.20 ± 0.58, respectively (p = 0.03).

Patients with HFrEF treated with sacubitril-valsartan exhibited significant improvements in cardiovascular outcomes despite AKI.

Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM.

We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10 years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27 647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5 years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10 year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD + HF and 2.43 (95% CI 2.29-2.58) for CKD + HF + DM.

In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.

Myocardial ischemia-reperfusion (MI/R) occurs due to temporary or permanent interruptions in the coronary and circulatory system, indirectly affecting kidney function through reduced cardiac output for metabolic needs. In this study, the aim was to explore the indirect effects of using human amniotic membrane mesenchymal stem cells (hAMSCs) with the PGS-co-PCL/PGC/PPy/Gelatin scaffold in male rats with renal failure induced by miocardial ischemia-reperfusion.

MI/R injury was induced in 48 male Wistar rats through left anterior descending artery ligation, divided into four groups (n=12); control group, cell group, scaffold group, and celss+scaffold group. Evaluations were conducted at two and thirty days post MI/R injury, encompassing echocardiography, biochemical, inflammatory markers analysis, and histological assessment.

Echocardiographic findings exhibited notable enhancement in ejection fraction, fractional shortening, and stroke volume of treated groups compared to controls after 30 days (P< 0.05). Serum creatinine (P< 0.001) and urea (P< 0.05) levels significantly decreased in the scaffold+cells group) compared to the control group. The treated cells+ scaffold group displayed improved kidney structure, evidenced by larger glomeruli and reduced Bowman's space compared to the control group (P< 0.01). Immunohistochemical analysis indicated reduced TNF-α protein in the scaffold+ cells group (P< 0.05) in contrast to the control group (P< 0.05). Inflammatory factors IL-6, TNF-α, and AKT gene expression in renal tissues were improved in scaffold+ cells-treated animals.

Our research proposes the combination of hAMSCs and the PGS-co-PCL/PGC/PPy/Gelatin scaffold in MI/R injured rats appears to enhance renal function and reduce kidney inflammation by improving cardiac output.

The term "Cardiorenal Syndrome" (CRS) refers to the complex interplay between heart and kidney dysfunction. First described by Robert Bright in 1836, CRS was brought to its modern view by Ronco et al. in 2008, who defined it as one organ's primary dysfunction leading to secondary dysfunction in the other, a view that led to the distinction of five different types depending on the organ of primary dysfunction and the temporal pattern (acute vs. chronic). Their pathophysiology is intricate, involving various hemodynamic, neurohormonal, and inflammatory processes that result in damage to both organs. While traditional biomarkers have been utilized for diagnosing and prognosticating CRS, they are inadequate for the early detection of acute renal damage. Hence, there is a pressing need to discover new biomarkers to enhance clinical outcomes and treatment approaches.

Goodpasture's syndrome (GPS) is a rare small vessel vasculitis characterized by circulating antibodies directed against the glomerular and alveolar basement membrane leading to renal and pulmonary manifestations. Here, we discuss a unique case of a 30-year-old Caucasian male smoker initially presenting with hemoptysis and anemia who was found to have biopsy-proven GPS with elevated anti-glomerular basement membrane (anti-GBM) antibodies. Unfortunately, the patient failed four months of standard treatment for GPS leading to end-stage renal disease (ESRD), while uniquely developing cardiorenal syndrome (CRS) with non-ischemic cardiomyopathy resulting in systolic and diastolic heart failure (HF). Despite aggressive medical management and hemodialysis, the patient's cardiac function continued to decline and the decision was made to insert an automatic implantable cardioverter defibrillator (AICD). To our knowledge, this is the first reported case of an anti-GBM-positive GPS patient who developed dilated cardiomyopathy. The importance of this report is to illustrate the rarity of developing CRS with non-ischemic cardiomyopathy and congestive heart failure from GPS and highlight the difficulty of determining management changes beyond guideline-directed medical therapy (GDMT) in GPS to slow the progression of worsening cardiac function.

Patients with end-stage heart disease who undergo a heart transplant frequently have simultaneous kidney insufficiency, therefore simultaneous heart and kidney transplantation is an option and it is necessary to understand its characteristics and long-term variables. The recipient characteristics and operative and long-term variables were assessed in a meta-analysis. A total of 781 studies were screened, and 33 were thoroughly reviewed. 15 retrospective cohort studies and 376 patients were included. The recipient's mean age was 51.1 years (95% CI 48.52-53.67) and 84% (95% CI 80-87) were male. 71% (95% CI 59-83) of the recipients were dialysis dependent. The most common indication was ischemic cardiomyopathy [47% (95% CI 41-53)] and cardiorenal syndrome [22% (95% CI 9-35)]. Also, 33% (95% CI 20-46) of the patients presented with delayed graft function. During the mean follow-up period of 67.49 months (95% CI 45.64-89.33), simultaneous rejection episodes of both organ allografts were described in 5 cases only. Overall survival was 95% (95% CI 88-100) at 30 days, 81% (95% CI 76-86) at 1 year, 79% (95% CI 71-87) at 3, and 71% (95% CI 59-83) at 5 years. Simultaneous heart and kidney transplantation is an important option for concurrent cardiac and renal dysfunction and has acceptable rejection and survival rates.

In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.

We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.

In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p<0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p<0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P<0.001).

In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.

With the development of pathophysiology, cardiorenal syndrome (CRS), a complex and severe disease, has received increasing attention. Monocyte to high-density lipoprotein-cholesterol ratio (MHR) and body mass index (BMI) are independent risk factors for cardiovascular diseases, but their association with CRS remains unexplored. This study aims to explore the independent and joint effects of MHR and BMI on CRS.

We included 42,178 NHANES participants. The determination of CRS referred to the simultaneous presence of cardiovascular disease (identified through self-report) and chronic kidney disease (eGFR < 60 mL/min per 1.73 m²). We employed multivariate weighted logistic regression to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the independent and joint associations of MHR and BMI with CRS. We also conducted restricted cubic spines to explore nonlinear associations.

The prevalence of CRS was 3.45% among all participants. An increase in both MHR and BMI is associated with a higher risk of CRS (MHR: OR = 1.799, 95% CI = 1.520-2.129, P < 0.001, P-trend < 0.001; BMI: OR = 1.037, 95% CI = 1.023-1.051, P < 0.001). Individuals who simultaneously fall into the highest quartile of MHR and have a BMI of 30 or more face the highest risk of CRS compared to those in the lowest MHR quartile with a BMI of less than 25 (OR = 3.45, 95% CI = 2.40-4.98, P < 0.001). However, there is no interactive association between MHR and BMI with CRS.

Higher MHR and BMI are associated with higher odds of CRS. MHR and BMI can serve as tools for early prevention and intervention of CRS, respectively.

Ubiquitin-specific protease 18 (USP18) is a protein recognized for its dual enzymatic and non-enzymatic nature. It is involved in many physiological processes like the cell cycle and cell signaling. It also suppresses heart muscle remodeling upon an increase in the afterload. The role of USP18 in kidney pathology remains unknown. The objective of the study was to assess the relationship between serum and urine USP18 levels, the factors contributing to cardiovascular risk, and the markers of kidney disease activity at different stages of chronic kidney disease (CKD). One hundred participants, aged between 24 and 85 years (mean 53.1 ± 17.1 years), were included. Five groups (n = 20 each) were recruited according to their renal status (healthy individuals, patients with proteinuric glomerulonephritis, patients with non-proteinuric CKD, patients who were treated with hemodialysis, and kidney transplant recipients). The measurements of serum and urine USP18 levels were performed using ELISA. The median serum USP18 level was the highest in healthy participants (1143.0 pg/mL) and kidney transplant recipients (856.6 pg/mL), whereas, in individuals with different forms of CKD, it fitted within the range of 402.1-471.9 pg/mL. Urinary USP18 reached the highest level in the group of CKD patients not yet on dialysis (303.3 pg/mL). Only in this group did it correlate with serum creatinine and urea concentrations. Our results suggest the inhibition of cardioprotective USP18 signaling when kidney function is impaired. Moreover, an increased level of urinary USP18 may indicate chronic tubular damage.

Atrazine (ATZ) is the most prevalent herbicide that has been widely used in agriculture to control broadleaf weeds and improve crop yield and quality. The heavy use of ATZ has caused serious environmental pollution and toxicity to human health. Lycopene (LYC), is a carotenoid that exhibits numerous health benefits, such as prevention of cardiovascular diseases and nephropathy. However, it remains unclear that whether ATZ causes cardiorenal injury or even cardiorenal syndrome (CRS) and the beneficial role of LYC on it. To test this hypothesis, mice were treated with LYC and/or ATZ for 21 days by oral gavage. This study demonstrated that ATZ exposure caused cardiorenal morphological alterations, and several inflammatory cell infiltrations mediated by activating NF-κB signaling pathways. Interestingly, dysregulation of MAPK signaling pathways and MAPK phosphorylation caused by ATZ have been implicated in cardiorenal diseases. ATZ exposure up-regulated cardiac and renal injury associated biomarkers levels that suggested the occurrence of CRS. However, these all changes were reverted, and the phenomenon of CAR was disappeared by LYC co-treatment. Based on our findings, we postulated a novel mechanism to elucidate pesticide-induced CRS and indicated that LYC can be a preventive and therapeutic agent for treating CRS by targeting MAPK/NF-κB signaling pathways.

Cardiac sarcoidosis (CS) is frequently associated with conduction abnormalities and arrhythmias. In this study, we aim to evaluate racial disparities in the frequency of arrhythmias, and associated co-morbidities, among patients with CS.

White and African American (AA) patients diagnosed with CS were identified and compared from the 2016-2020 National Inpatient Sample (NIS) database whilst adjusting for confounders via logistic regression models.

A total of 7,935 patients with CS were included in the study. The propensity-matched sample comprised of 5,570 patients, of whom 2,785 were White and 2,785 were AA. AA patients had a longer mean length of hospital stay (LOS) (7.84 vs. 6.94, p<0.01), a higher mean Charlson Comorbidity Index (CCI) score (3.10 vs. 2.84, p<0.01), and significantly higher incidences of cardiogenic shock [(9.2% vs 6.3%, p<0.01), aOR 1.45 (95% CI 1.17-1.78), p<0.01] and acute kidney injury (AKI) [(34.3% vs. 26.9%, p<0.01), aOR 1.41 (95% CI 1.24-1.61), p<0.01]. From an arrhythmia perspective, AA CS patients were shown to have a lower frequency of: (1) ventricular tachycardia (32.5% vs. 37.9%, p<0.01), (2) ventricular fibrillation (5.4% vs.7.2%, p<0.01), (3) first-degree AV block (1.8% vs. 4.1%, p<0.01), (4) complete AV block (6.3% vs. 14.2%, p<0.01), and (5) atrial fibrillation (31.8% vs. 34.8%, p=0.016) when compared to Whites with CS. Mortality remained higher for AAs (3.8% vs. 2.7%, p=0.024).

Our study demonstrates a higher incidence of cardiac arrhythmias among White patients but a higher incidence of cardiogenic shock, AKI, mean LOS, and mortality among AA patients with cardiac sarcoidosis.

MicroRNAs (miRNAs) are important regulatory factors in the normal developmental stages of the heart and kidney. However, it is currently unclear how miRNA is expressed in type 2 cardiorenal syndrome (CRS). This study aimed to detect the differential expression of miRNAs and to clarify the main enrichment pathways of differentially expressed miRNA target genes in type 2 CRS.

Five cases of healthy control (Group 1), eight of chronic heart failure (CHF, Group 2) and seven of type 2 CRS (Group 3) were enrolled, respectively. Total RNA was extracted from the peripheral blood of each group. To predict the miRNA target genes and biological signalling pathways closely related to type 2 CRS, the Agilent miRNA microarray platform was used for miRNA profiling and bioinformatics analysis of the isolated total RNA samples.

After the microarray analysis was done to screen for differentially expressed circulating miRNAs among the three different groups of samples, the target genes and bioinformatic pathways of the differential miRNAs were predicted. A total of 38 differential miRNAs (15 up- and 23 down-regulated) were found in Group 3 compared with Group 1, and a total of 42 differential miRNAs (11 up- and 31 down-regulated) were found in Group 3 compared to Group 2. According to the Gene Ontology (GO) function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, the top 10 lists of molecular functions, cellular composition and biological processes, and the top 30 signalling pathways of predicted gene targets of the differentially expressed miRNAs were discriminated among the three groups.

Between the patients with CHF and type 2 CRS, miRNAs were differentially expressed. Prediction of target genes of differentially expressed miRNAs and the use of GO function and KEGG pathway analysis may reveal the molecular mechanisms of CRS. Circulating miRNAs may contribute to the diagnosis of CRS, and further and larger studies are needed to enhance the robustness of our findings.

Chronic kidney disease (CKD) guidelines recommend early identification and intervention to delay the progression of CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) heatmap is widely used for risk evaluation in CKD management; however, real-world evidence on clinical characteristics based on the KDIGO heatmap remains limited worldwide including Japan. In order to understand the management of CKD including its diagnostic rates in a Japanese clinical setting on the basis of KDIGO heatmap, we utilized a medical record database that contains estimated glomerular filtration rate (eGFR) and urine protein data. Adult individuals (≥ 18 years) with two eGFR results of < 90 mL/min/1.73 m2, 90-360 days apart, were included. Approximately half of patients (452,996/788,059) had proteinuria test results and 6.9% (54,073) had quantitative results. CKD diagnosis rate in patients without proteinuria data was 5.9%, with a lower rate (2.9%) in stage G2; the corresponding rates with quantitative test results were 43.5% and 31.3%, respectively. The most frequent comorbidities were hypertension, diabetes, and cardiovascular disease, and their prevalence increased as the eGFR and proteinuria stages progressed. This study revealed a low rate of proteinuria assessment, especially using quantitative methods, and diagnosis in individuals with suspected CKD. With emerging treatment options to prevent CKD progression and complication onset, there is a need for early evaluation and diagnosis of CKD.

The unfavorable mutual influence of the kidney and heart functions in acute or chronic kidney and/or heart failure has defined the cardiorenal syndrome (CRS) since a consensus conference in 2004. The pathophysiological considerations and the subsequent treatment approaches determine the classification into five types. The syndrome has a high prevalence in geriatric patients. The interactions of medications on one or the other organ system require an interaction of treatment modalities in order to improve the prognosis and prevent acute deterioration. Exact knowledge of the respective indications, differential treatment approaches and specifics in dealing with CRS can improve the current undertreatment due to concerns about side effects.

To date, the complex pathological interactions between renal and cardiovascular systems represent a real global epidemic in both developed and developing countries. In this context, renovascular hypertension (RVH) remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation. Adult male Wistar rats underwent unilateral renal artery ligation and treatment with deoxycorticosterone acetate (DOCA) (20 mg/kg, s.c.), twice a week for a period of 4 weeks, and 1% sodium chloride (NaCl) water (n = 10). A subgroup of hypertensive rats received BPF (100 mg/kg/day for 28 consecutive days, n = 10) by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (that served as control, n = 8). Unilateral renal artery ligation followed by treatment with DOCA and 1% NaCl water resulted in a significant increase in mean arterial blood pressure (MAP; p< 0.05. vs CTRL) which strongly increased the resistive index (RI; p<0.05 vs CTRL) of contralateral renal artery flow and kidney volume after 4 weeks (p<0.001 vs CTRL). Renal dysfunction also led to a dysfunction of cardiac tissue strain associated with overt dyssynchrony in cardiac wall motion when compared to CTRL group, as shown by the increased time-to-peak (T2P; p<0.05) and the decreased whole peak capacity (Pk; p<0.01) in displacement and strain rate (p<0.05, respectively) in longitudinal motion. Consequently, the hearts of RAL DOCA-Salt rats showed a larger time delay between the fastest and the lowest region (Maximum Opposite Wall Delay-MOWD) when compared to CTRL group (p<0.05 in displacement and p <0.01 in strain rate). Furthermore, a significant increase in the levels of the circulating pro-inflammatory cytokines and chemokines (p< 0.05 for IL-12(40), p< 0.01 for GM-CSF, KC, IL-13, and TNF- α) and in the NGAL expression of the ligated kidney (p< 0.001) was observed compared to CTRL group. Interestingly, this pathological condition is prevented by BPF treatment. In particular, BPF treatment prevents the increase of blood pressure in RAL DOCA-Salt rats (p< 0.05) and exerts a protective effect on the volume of the contralateral kidney (p <0.01). Moreover, BPF ameliorates cardiac tissue strain dysfunction by increasing Pk in displacement (p <0.01) and reducing the T2P in strain rate motion (p<0.05). These latter effects significantly improve MOWD (p <0.05) preventing the overt dyssynchrony in cardiac wall motion. Finally, the reno-cardiac protective effect of BPF was associated with a significant reduction in serum level of some pro-inflammatory cytokines and chemokines (p<0.05 for KC and IL-12(40), p<0.01 for GM-CSF, IL-13, and TNF- α) restoring physiological levels of renal neutrophil gelatinase-associated lipocalin (NGAL, p<0.05) protein of the tethered kidney. In conclusion, the present results show, for the first time, that BPF promotes an efficient renovascular protection preventing the progression of inflammation and reno-cardiac damage. Overall, these data point to a potential clinical and veterinary role of dietary supplementation with the polyphenol-rich fraction of citrus bergamot in counteracting hypertension-induced reno-cardiac syndrome.

The present study aimed to identify optimal inflammatory biomarkers involved in cardiorenal risk in response to major lifestyle factors.