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Cardiorenal diseases represent a complex interplay between heart failure and renal dysfunction, being clinically classified as cardiorenal syndromes (CRS). Recently, the contributions of altered nicotinamide adenine dinucleotide (NAD+) metabolism, through deficient NAD+ synthesis and/or elevated consumption, have proved to be decisive in the onset and progress of cardiorenal disease. NAD+ is a pivotal coenzyme in cellular metabolism, being significant in various signaling pathways, such as energy metabolism, DNA damage repair, gene expression, and stress response. Convincing evidence suggests that strategies designed to boost cellular NAD+ levels are a promising therapeutic option to address cardiovascular and renal disorders. Here, we review and discuss the implications of NAD+ metabolism in cardiorenal diseases, focusing on the propitious NAD+ boosting therapeutic strategies, based on the use of NAD+ precursors, poly(ADP-ribose) polymerase inhibitors, sirtuin activators, and other alternative approaches, such as CD38 blockade, nicotinamide phosphoribosyltransferase activation and combined interventions. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

The article examines the usage patterns of SGLT2 inhibitors among high-risk CKM patients within the Mass General Brigham (MGB) healthcare system.

The development of aortic insufficiency (AI) during HeartMate 3 durable left ventricular assist device (dLVAD) support can lead to ineffective pump output and recurrent heart failure symptoms. Progression of AI often comingles with the occurrence of other hemodynamic-related events encountered during LVAD support, including right heart failure, arrhythmias, and cardiorenal syndrome. While data on AI burdens and clinical impact are still insufficient in patients on HeartMate 3 support, moderate or worse AI occurs in approximately 8% of patients by 1 year and studies suggest AI continues to progress over time and is associated with increased frequency of right heart failure. The first line intervention for AI management is prevention, undertaking surgical intervention on the insufficient valve at the time of dLVAD implant and avoiding excessive device flows and hypertension during long-term support. Device speed augmentation may then be undertaken to try and overcome the insufficient lesion, but the progression of AI should be anticipated over the long term. Surgical or transcatheter aortic valve interventions may be considered in dLVAD patients with significant persistent AI despite medical management, but neither intervention is without risk. It is imperative that future studies of dLVAD support capture AI in clinical end-points using uniform assessment and grading of AI severity by individuals trained in AI assessment during dLVAD support. [Display omitted] [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD–PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patients at high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD–PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD–PH. In this Review, the authors discuss potential pathophenotypes of coexisting chronic kidney disease and pulmonary hypertension, discuss the principles of clinical management of patients with chronic kidney disease or kidney failure and pulmonary hypertension, and outline key areas for further research. Key points: Pulmonary hypertension (PH) is common and independently associated with increased mortality in patients with chronic kidney disease or kidney failure; conversely, chronic kidney disease and kidney failure are common and independently associated with increased mortality in patients with PH. In left-heart cardiorenal syndrome, impaired left ventricular function leads to pulmonary venous hypertension, which promotes pulmonary hypertension as well as renal dysfunction in the setting of renin–angiotensin–aldosterone system overactivation, salt avidity and hypervolaemia. In right-heart cardiorenal syndrome, pulmonary arterial hypertension leads to severe pulmonary arterial remodelling, right-heart failure and impaired cardiac output, despite normal left-heart function. This process promotes kidney failure via neurohumoral, sympathetic and mechanical mechanisms. Major overlap exists in the pathophysiology of pulmonary arterial remodelling and kidney failure, which could serve as the basis for potential therapeutic targets for both conditions. No clear screening algorithms have been established for PH in kidney failure or kidney failure in PH. PH could be a potential surrogate marker for risk of kidney failure, and opportunities may exist to improve outcomes by considering PH when determining the timing and appropriateness of kidney replacement therapy and/or kidney transplantation. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated whether the oral vasopressin V2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet–cold pattern), from the viewpoint of cardiorenal syndrome. Methods: Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria–Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups. Results: Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet–cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417). Conclusion: There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

G protein‐coupled receptor (GPCR) kinase 2 (GRK2) is an integrative node in many signalling network cascades. An emerging study indicates that GRK2 can interact with GPCRs and non‐GPCR substrates in both kinase‐dependent and ‐independent modes. Alterations in the functional levels of GRK2 have been found in a variety of renal diseases, such as hypertension‐related kidney injury, sepsis‐associated acute kidney injury (S‐AKI), cardiorenal syndrome (CRS), acute kidney injury (AKI), age‐related kidney injury or hyperglycemia‐related kidney injury. Abnormal GRK2 expression contribute to the development of renal diseases, making them promising molecular targets for treating renal diseases. Blocking the prostaglandin E2 (PGE2)‐EP1‐Gaq‐Ca2+ signal pathway in glomerular mesangial cells (GMCs) by internalizing prostaglandin E2 receptor 1 (EP1) with GRK2 may be a potential treatment for diabetic nephropathy (DN). In addition, GRK2 inhibition may have therapeutic effects in a variety of renal diseases, such as SLE‐related kidney injury, DN, age‐related kidney injury, hypertension‐related kidney injury, and CRS. However, there is still a long way to go for the large‐scale application of GRK2 inhibition in the field of renal diseases. In this review, we discuss recent updates in understanding the role of GRK2 in kidney dysfunction. Furthermore, we explore the potential of GRK2 as a possible therapeutic target for renal pathologies. We believe it will shed light on the future development of small‐molecule inhibitors of GRK, as well as the clinical applications in renal diseases. [ABSTRACT FROM AUTHOR]

Background Cardiorenal syndrome highlights the bidirectional relationship between kidney and heart dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is the gold standard biomarker in heart failure (HF), may be an important biomarker for chronic kidney disease (CKD) progression. However, NT-proBNP is negatively related with estimated glomerular filtration rate (eGFR). In this study, we investigated the association of NT-proBNP, eGFR, and progression of kidney disease in CKD patients without HF. Methods This multicentric retrospective cohort study recruited 23 860 CKD patients without HF, who had at least one NT-proBNP record from China Renal Data System database. Linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. Sensitivity analysis examined the robustness of the main findings. Results This study involved 23 860 CKD patients without HF, distributed across different CKD stages: 10 526 in stages G1-2, 4665 in G3a, 3702 in G3b, 2704 in G4, and 2263 in G5. NT-proBNP was negatively correlated with eGFR, particularly in stages 4–5 CKD. A 15-unit decrease in eGFR was associated with increases in log (NT-proBNP) levels by 1.04-fold, 1.27-fold, 1.29-fold, 1.80-fold, and 3.50-fold for stages 1–2, 3a, 3b, 4, and 5, respectively. After excluding patients who developed CKD progression within 1 year, the Cox regression analysis revealed that the relationship between NT-proBNP and CKD progression was not significant in stages 4 and 5. However, for stages 1–3, each standard deviation increase in log (NT-proBNP) was associated with a 26%, 36%, and 28% higher risk of CKD progression, with P interaction ≤.001. The hazard ratios were 1.26 (95% confidence intervals (CI), 1.18 to 1.35), 1.36 (95% CI, 1.22 to 1.51), and 1.28 (95% CI, 1.14 to 1.43) for stages 1–2, stage 3a, and stage 3b, respectively. Conclusions Despite its strong inverse association with eGFR, NT-proBNP was positively associated with the risk of progression of kidney disease in CKD patients with stages 1–3 without HF. Future studies should investigate the effectiveness of NT-proBNP as a predictive biomarker for the progression of kidney disease across diverse racial groups and healthcare settings. [ABSTRACT FROM AUTHOR]

Background/Objectives: Multi-organ failure (MOF) often complicates advanced heart failure (HF), contributing to a poor prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale incorporates liver and kidney function parameters. This study aims to evaluate the prognostic significance of the MELD-3.0 score in patients with advanced HF who have undergone heart transplantation (HTx). Methods: The MELD-3.0 score was computed using the average values of the international normalized ratio and bilirubin, creatinine, sodium, and albumin levels during a hospital stay following HTx. The average MELD-3.0 scores from the period of 1 month preceding HTx and 1 week after HTx were analyzed. The primary endpoint of the study was the 6-month total mortality, and the secondary endpoint was ICU hospitalization time after HTx. Results: The analysis included 106 patients undergoing HTx, with a median age of 53 years (44–63), 81% of whom were male. Within 6 months post-HTx, 17 patients (16%) died; those patients had a higher 1-week post-HTx MELD-3.0 score of 18.3 (14.5–22.7) in comparison to survivors, whose average score was 13.9 (9.5–16.4), p < 0.01. There was no difference in MELD 3.0 score in the pre-HTx period: 16.6 (11.4–17.8) vs. 12.3 (8.6–17.1), p = 0.36. The post-HTx MELD-3.0 score independently predicted death: RR 1.17 (95% CI 1.05–1.30), p < 0.01. A Receiver Operating Characteristic (ROC) determined the cut-off value of the MELD-3.0 score as 17.3 (AUC = 0.83; sensitivity—67%; specificity—86%). Survivors with scores above this value had a longer ICU hospitalization time: 7 (5.0–11.0) vs. 12 (8–20) days (p = 0.01). Conclusions: The post-HTx MELD-3.0 score serves as an independent predictor of an unfavorable prognosis in patients with advanced HF undergoing HTx. The evaluation of MELD-3.0 scores provides additional prognostic information in this population. [ABSTRACT FROM AUTHOR]

Heart failure and chronic kidney disease are common and clinically important conditions that regularly coexist. Electrophysiologic changes of advanced heart failure often result in abnormal conduction, causing dyssynchronous contraction, and development of ventricular arrhythmias, which can lead to sudden cardiac arrest. In the last 2 decades, implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been developed to address these complications. However, when the coexisting chronic kidney disease is advanced, the associated pathophysiologic cardiovascular changes can alter the efficacy and safety of those interventions and complicate the management. This review explores the impact of comorbid advanced heart failure and advanced chronic kidney disease on the efficacy and safety of implantable cardioverter-defibrillator and cardiac resynchronization therapy, the currently available evidence, and potential future directions. [Display omitted] • The efficacy and safety of ICD and CRT devices have not been established for patients with advanced CKD, and available data suggest that they may be less favorable than in patients without advanced CKD. • Factors limiting the effectiveness of these devices in patients with advanced CKD include the frequency of nonshockable arrhythmias, increased defibrillation thresholds, noncapture, myocardial fibrosis, coexisting atrial fibrillation, limited use of guideline-directed therapies for heart failure, and relatively high rates of nonarrhythmic mortality. • Randomized trials are needed to improve selection of patients with advanced CKD for these device-based therapies. [ABSTRACT FROM AUTHOR]

Abstract: The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis. [ABSTRACT FROM AUTHOR]

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in terms of the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption of large amounts of ultrafiltrate and dissolved substances. The place of action of oxidative stress is the influence on the balance in the production and breakdown of the mitochondrial reactive oxygen species. A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future. This underscores the urgent need for further research. The narrative review integrates results found in previously performed studies that have evaluated oxidative stress participation in cardiorenal syndrome type 3. [ABSTRACT FROM AUTHOR]

Background Cardiorenal syndrome is a common condition in clinical practice in which renal venous congestion (VC) plays an important role. Intrarenal Doppler ultrasound (IRD) is a non-invasive method to assess and quantify renal VC. The current study aims to investigate the effects of SGLT2 inhibitor (SGLT2i) therapy on IRD parameters of renal VC. Methods This prospective observational study included patients with chronic kidney disease (CKD) with or without type 2 diabetes mellitus and/or heart failure (HF) with reduced and preserved ejection fraction who had an indication for standard of care SGLT2i therapy. IRD, assessing venous impedance index (VII), and intrarenal venous flow pattern (IRVF) analysis were performed within the interlobar vessels of the right kidney before and 6 months after initiation of SGLT2i therapy. Results A number of 64 patients with CKD and a cardiorenal risk profile were included (mean eGFR 42.9 ml/min/1.73 m2; 56% with HF, and 38% with type 2 diabetes mellitus). 17 patients exhibited signs of VC in the IRD. VII was significantly correlated with levels of NT-proBNP, female gender, NYHA class, and was significantly negative correlated with body mass index. After 6 months, a notable decrease in the mean VII of the right interlobar veins by 0.13 (P < .01) was observed. Stratification according to IRVF pattern showed a significant shift towards reduced renal VC pattern after 6 months (P = .03). Conclusions In this study, SGLT2i therapy resulted in a reduction in renal VC as assessed by IRD. These findings underscore the potential haemodynamic benefits of SGLT2 inhibitors in cardiorenal syndrome and warrant further investigation into their clinical implications. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) is a life-threatening disorder that involves a complex interplay between the two organs. Managing this multifaceted syndrome is challenging in the hospital and requires a multidisciplinary approach to tackle the many manifestations and complications. There is no universally accepted algorithm to treat patients, and therapeutic options vary from one patient to another. The mainstays of therapy involve the stabilization of hemodynamics, decongestion using diuretics or renal replacement therapy, improvement of cardiac output with inotropes, and goal-directed medical treatment with renin–angiotensin–aldosterone system inhibitors, beta-blockers, and other medications. Mechanical circulatory support is another viable option in the armamentarium of agents that improve symptoms in select patients. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for type 2 diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) and chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis of the multifaceted mechanisms underlying the cardiorenal benefits of SGLT2i in HF and CKD outside of the T2D context. Eight major aspects of the protective effects of SGLT2i beyond glycemic control are explored: 1) the impact on renal hemodynamics and tubuloglomerular feedback; 2) the natriuretic effects via proximal tubule Na+/H+ exchanger NHE3 inhibition; 3) the modulation of neurohumoral pathways with evidence of attenuated sympathetic activity; 4) the impact on erythropoiesis, not only in the context of local hypoxia but also systemic inflammation and iron regulation; 5) the uricosuria and mitigation of the hyperuricemic environment in cardiorenal syndromes; 6) the multiorgan metabolic reprogramming including the potential induction of a fasting-like state, improvement in glucose and insulin tolerance, and stimulation of lipolysis and ketogenesis; 7) the vascular endothelial growth factor A (VEGF-A) upregulation and angiogenesis, and 8) the direct cardiac effects. The intricate interplay between renal, neurohumoral, metabolic, and cardiac effects underscores the complexity of SGLT2i actions and provides valuable insights into their therapeutic implications for HF and CKD. Furthermore, this review sets the stage for future research to evaluate the individual contributions of these mechanisms in diverse clinical settings. [ABSTRACT FROM AUTHOR]

Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram. In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort. The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009–1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193–6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012–1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96-–0.987; p < 0.001), homocysteine (OR = 1.05; 95%CI = 1.03–1.069; p < 0.001), AKI stage [(stage 1: reference), (stage 2: OR = 5.427; 95%CI = 1.781–16.534; p = 0.003), (stage 3: OR = 5.554; 95%CI = 2.234–13.805; p < 0.001)]. The nomogram exhibited excellent predictive performance with an AUC of 0.907 in the study cohort and 0.892 in the validation cohort. Calibration and decision curve analyses upheld its accuracy and clinical utility. We developed a nomogram predicting CRS type 3 in AKI patients, incorporating 6 risk factors: age, CVD history, MAP, hemoglobin, homocysteine, and AKI stage, enhancing early risk identification and patient management. [ABSTRACT FROM AUTHOR]

Background Cardiorenal syndrome (CRS) type 1 defined as acute kidney injury (AKI) in acute decompensated heart failure (ADHF), is complicated due to diverse definitions. Recently, a more precise CRS type 1 definition was proposed, mandating concurrent AKI and signs of unimproved heart failure (HF). Our study explores the incidence, predictors, and long-term outcomes of AKI in ADHF under this new definition. Methods A prospective observation study of ADHF patients categorized into the CRS type 1, pseudo-CRS, and non-AKI groups, followed for 12 months. CRS type 1 involved AKI with clinical congestion, while pseudo-CRS included AKI with clinical decongestion (clinical congestion score

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

Background Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. Methods This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2). Results The mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0–13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r  = −0.43, P  < .001 and r  = −0.22, P  = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [β = 0.02 (95% confidence interval −0.19–0.23), P  = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620). Conclusions In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD. [ABSTRACT FROM AUTHOR]

In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) can lead to cardiac dysfunction in a condition known as cardiorenal syndrome (CRS). It is postulated that the accumulation of uremic toxins in the bloodstream, as a consequence of declining kidney function, may contribute to these adverse cardiac effects. While CRS in adults has been extensively studied, there is a significant knowledge gap with pediatric patients. Uremic toxin levels in children remain inadequately characterized and quantified compared to adults. This review aims to systematically evaluate the association between uremic toxin concentrations and cardiac changes in pediatric CRS and to examine the impact of different dialysis modalities, specifically hemodialysis and peritoneal dialysis, on uremic toxin clearance and cardiovascular parameters. To address this, we conducted a systematic literature search of PubMed, following PRISMA guidelines. We used the terms "uremic toxins" and "cardiorenal syndrome" with variations in syntax to search for studies discussing the relationship between uremic toxin levels in CKD, the subsequent impact on cardiac parameters, and the emergence of cardiac dysfunction. Full-text articles written in English, conducted on humans aged from birth to 18 years, and published until December 2021 were included. A comprehensive literature search yielded six studies, and their risk of bias was assessed using JBI Critical Appraisal Checklists. Our systematic review is registered on PROSPERO, number CRD42023460072. This synthesis intends to provide an understanding of the role of uremic toxins in pediatric CRS. The findings reveal that pediatric patients with end-stage CKD on dialysis exhibit elevated uremic toxin levels, which are significantly associated with cardiovascular disease parameters. Additionally, the severity of CKD correlated with higher uremic toxin levels. No conclusive evidence was found to support the superiority of either hemodialysis or peritoneal dialysis in terms of uremic toxin clearance or cardiovascular outcomes. More pediatric-specific standardized and longitudinal studies are needed to develop targeted treatments and improve clinical outcomes and the quality of life for affected children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right‐sided heart failure or intra‐abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion‐driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low‐grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation. [ABSTRACT FROM AUTHOR]

Aims: Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF). Methods and results: Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P < 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission. Conclusions: The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF. [ABSTRACT FROM AUTHOR]

Introduction: End-stage renal disease is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered contraindication for kidney transplant, although some patients demonstrate myocardial recovery post-transplant. We aimed to identify and characterize the phenomenon of reverse myocardial remodeling in kidney transplanted patients. Methods: The study is a retrospective cohort of patients undergoing kidney transplants between 2016 and 2019 (n = 604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. Results: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal to or above 5%, whereas 36 (12%) patients had a LVEF improvement of 10% or more post-transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5%, and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. Conclusion: Renal transplantation might lead to improved LV systolic function in some patients. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the correlation between different attributes, levels of biomarkers, and the probability of developing cardiorenal syndrome (CRS) in patients who have been diagnosed with type 2 diabetes mellitus (T2DM) and liver cirrhosis (LC). The hypothesis suggests that liver illness may be linked to renal impairment, cardiac dysfunction, and the development of cardiorenal syndrome Methods: The current study retrospectively assessed the medical records of patients who had LC and T2DM diagnoses and were hospitalized at Al Madina Al Munwara hospitals in 2022 and 2023. Original Article Results: This research investigated T2DM patients with physician-confirmed to have LC. Poor glycemic control is indicated by high blood glucose and glycated hemoglobin (HbA1c) readings in research participants. High blood pressure, atherogenic plasma indicator (AIP), and obesity plagued most of these individuals. High creatinine, moderate estimated Glomerular Filtration Rate (eGFR) decline, and a modest urinary albumin-to-creatinine (UACR) rise were the most prevalent variables in LC and T2DM patients. Cardiorenal syndrome risk factors, including elevated blood pressure, triglyceride levels, body mass index (BMI), and high-sensitivity C-reactive protein (hs-CRP) concentrations, were identified through logistic regression. It has been demonstrated that the prevalence of these risk factors increases with age; women may be at a greater risk for developing CRS. Specific biomarker evaluations classified 108 (22.6%) LC and T2DM patients at high risk for chronic kidney disease (CKD), 100 (20%) at risk for cardiovascular disease (CVD), and 91 (18.2%) at risk for CRS. Conclusion: The current assessment included 500 patients with T2DM and LC. The risk factors for CRS identified in this study included elevated cholesterol and triglyceride levels, high BMI, and elevated blood pressure, with age being a significant factor, particularly in female patients. Early identification of these characteristics in patients with LC and T2DM could aid in mitigating the progression of chronic illnesses and their associated complications. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac implantable electrical devices are able to affect kidney function through hemodynamic improvements. The cardiac contractility modulation (CCM) is a device-based therapy option for patients with symptomatic chronic heart failure (HF) despite optimized medical treatment. The long-term cardiorenal interactions for CCM treated patients are yet to be described. Methods: CCM recipients (n = 187) from the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) were evaluated in the long-term (up to 60 months) for changes in serum creatinine, estimated glomerular filtration rate (eGFR), other surrogate markers of kidney function, and the chronic kidney disease (CKD) stage distribution. With regard to kidney function at baseline, the patients were furthermore grouped to either advanced CKD (aCKD, CKD stage ≥3, eGFR≤59 mL/min/1.73 m2, n = 107) or preserved kidney function and mild CKD (pCKD, CKD stages 1–2, eGFR≥60 mL/min/1.73 m2, n = 80). The groups were compared for differences regarding kidney function, New York Heart Association classification (NYHA), biventricular systolic function, HF hospitalizations and other parameters in the long-term (60 months). Results: CKD stage distribution remained stable during the entire follow-up (p = 0.65). An increase in serum creatinine (1.47 ± 1 vs. 1.6±1 mg/dL) with a corresponding decline of eGFR (58.2 ± 23.4 vs. 54.2 ± 24.4 mL/min/1.73 m2, both p < 0.05) were seen after 60 months but not before for the total cohort, which was only significant in pCKD patients in terms of group comparison. Mean survival (54.3 ± 1.3 vs. 55.3 ± 1.2 months, p = 0.53) was comparable in both groups. Improvements in NYHA (3.11 ± 0.46 vs. 2.94 ± 0.41–2.28 ± 0.8 vs. 1.94 ± 0.6) and LVEF (24.8 ± 7.1 vs. 22.9 ± 6.6–31.1 ± 11.4 vs. 35.5 ± 11.1%) were likewise similar after 60 months (both p < 0.05). The aCKD patients suffered from more HF hospitalizations and ventricular tachycardias during the entire follow-up period (both p < 0.05). Conclusions: The kidney function parameters and CKD stage distribution might remain stable in CCM treated HF patients in the long-term, who experience improvements in LVEF and functional status, regardless of their kidney function before. An impaired kidney function might be associated with further cardiovascular comorbidities and more advanced HF before CCM, and could be an additional risk factor of HF complications afterward. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cardiorenal syndrome (CRS) is a disorder of the heart and kidneys, with one type of organ dysfunction affecting the other. The pathophysiology is complex, and its actual description has been questioned. We used clustering analysis to identify clinically relevant phenogroups among patients with CRS. Methods: Data for patients admitted from 1 January 2012 to 31 December 2012 were collected from the French national medico-administrative database. Patients with a diagnosis of heart failure and chronic kidney disease and at least 5 years of follow-up were included. Results: In total, 13,665 patients were included and four clusters were identified. Cluster 1 could be described as the vascular–diabetes cluster. It comprised 1930 patients (14.1%), among which 60% had diabetes, 94% had coronary artery disease (CAD), and 80% had peripheral artery disease (PAD). Cluster 2 could be described as the vascular cluster. It comprised 2487 patients (18.2%), among which 33% had diabetes, 85% had CAD, and 78% had PAD. Cluster 3 could be described as the metabolic cluster. It comprised 2163 patients (15.8%), among which 87% had diabetes, 67% dyslipidemia, and 62% obesity. Cluster 4 comprised 7085 patients (51.8%) and could be described as the low-vascular cluster. The vascular cluster was the only one associated with a higher risk of cardiovascular death (HR: 1.48 [1.32–1.66]). The metabolic cluster was associated with a higher risk of kidney replacement therapy (HR: 1.33 [1.17–1.51]). Conclusions: Our study supports a new classification of CRS based on the vascular aspect of pathophysiology differentiating microvascular or macrovascular lesions. These results could have an impact on patients' medical treatment. [ABSTRACT FROM AUTHOR]

Background: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). Methods: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal–Wallis analysis were performed using SAS version 9.4. Results: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). Conclusions: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein. [ABSTRACT FROM AUTHOR]

Purpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients. Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I. Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642– 0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781– 0.834) to 0.825 (95% CI=0.799– 0.850). Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice. [ABSTRACT FROM AUTHOR]

In recent decades, there has been considerable effort in investigating the clinical utility of renal Doppler measurements in both cardiovascular and renal disorders. In particular, a measure of renal arterial resistance, the renal resistive index (RRI), has been demonstrated to predict chronic kidney disease progression and acute kidney injury in different clinical settings. Furthermore, it is linked to a poorer prognosis in individuals suffering from chronic heart failure. Examining the renal venous flow through pulsed Doppler can offer additional insights into renal congestion and cardiovascular outcomes for these patients. This review seeks to summarize the existing data concerning the clinical significance of arterial and venous renal Doppler measurements across various cardiovascular and renal disease contexts. [ABSTRACT FROM AUTHOR]

The article discusses the impact of pulmonary hypertension (PH) on patients with heart failure (HF). PH is frequently seen in HF patients and is associated with increased mortality. The article highlights the updated definitions of PH and pre-capillary PH provided by the European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines. The study by Fauvel et al. demonstrates that the refined definitions of PH and pre-capillary PH are valid and that patients with values above the new thresholds are at increased risk of adverse outcomes. The article also mentions the need for further research on the prognostic implications and therapeutic options for PH in HF patients. [Extracted from the article]

The article discusses the concept of cardio-renal problems, specifically the cardiovascular-kidney-metabolic syndrome (CKM) and the chronic cardiovascular-kidney disorder (CCKD). The CKM is characterized by a cluster of metabolic risk factors that impact the kidneys and cardiovascular system, while the CCKD focuses on concomitant cardiovascular and kidney problems independently of their chronology. Both concepts emphasize the complexity of managing patients with these conditions and the need for interdisciplinary care models, lifestyle modifications, and innovative treatment strategies. The article also highlights the importance of addressing social determinants of health and conducting comprehensive research to better understand these conditions. [Extracted from the article]