Cardiorenal Medicine最新文献

Background: Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) have a strong pathophysiological interrelationship, and their combination worsens prognosis.

Summary: This article briefly reviews the bidirectional epidemiological burden and the pathophysiological interplay between HFpEF and CKD. It also discusses some of the controversial aspects regarding the diagnosis and screening of HFpEF in CKD patients and focuses on the most effective therapeutic approaches to improve symptoms and prognosis in this high-risk population.

Key messages: Due to its prevalence and prognostic significance, HFpEF screening should be considered in patients with CKD, with careful use of traditional diagnostic tools in this population. Optimal medical therapy has seen major recent advances in patients with both HFpEF and CKD. SGLT2 inhibitors, finerenone, and semaglutide have consistently demonstrated cardio- and renoprotective effects in both conditions.

Introduction: Worsening renal function (WRF) is associated with poor prognosis in patients with heart failure (HF). Osteopontin (OPN) and matrix extracellular phosphoglycoprotein (MEPE) are expressed in the kidneys and are involved in bone mineralization processes. Higher OPN levels have been associated with a higher risk for adverse outcomes in patients with chronic kidney disease (CKD), and MEPE has been shown to promote renal phosphate excretion. Here, we explored if MEPE and OPN are associated with WRF and CKD in patients admitted for acute HF.

Methods: WRF was defined as an increase in plasma creatinine of >26.5 mmol/L or 50% higher than admission concentration within 48 h of admission. OPN and MEPE were analyzed in 315 HF patients at baseline, and in 120 patients at 6-month follow-up. Associations between MEPE and OPN, and (a) WRF, (b) CKD stage 3-5, and (c) markers of kidney function were explored. Further, OPN and MEPE at baseline and at 6-month follow-up (delta [Δ] values) were related to CKD progression.

Results: The study population had a mean age of 75 (±12) years and 31% were women. Higher levels of MEPE and OPN were associated with WRF (n = 30; OR 2.80; [1.49-5.25]; p = 0.001, and OR 1.84; [1.05-3.23]; p = 0.034, respectively). On admission, both MEPE and OPN were associated with CKD stage 3-5 (OR 5.27; [2.76-10.07]; p < 0.001, and OR 3.26; [1.90-5.60]; p < 0.001, respectively). At 6-month follow-up, progression in CKD stage was associated with ΔMEPE and ΔOPN (HR 2.53; [1.48-4.31]; p < 0.001, and HR 2.66; [1.51-4.71]; p < 0.001).

Conclusion: Here, MEPE and OPN are for the first time shown to be independently associated with WRF and subsequent deterioration in CKD in a HF cohort. The mechanisms of these associations are currently largely unknown and need to be investigated further.

Introduction: Fat-free mass (FFM) is a critical component of the human body, with implications for various diseases.

Methods: We conducted a comprehensive analysis integrating a phenome-wide association study (PheWAS), a two-sample Mendelian randomization (MR) analysis, and a systematic review to investigate the associations between FFM and health outcomes.

Results: PheWAS identified 183 phenotypes enriched for FFM associations, including diseases, body composition, and lifestyle factors. A two-sample MR analysis using the FinnGen and UK Biobank dataset revealed significant associations between genetically determined FFM and 36 disease outcomes, including cardiovascular diseases, metabolic disorders, and musculoskeletal conditions. The mediation MR analysis indicates that FFM indirectly influences the levels of five biomarkers in visceral adipose tissue. A systematic review identified consistent associations between FFM and several diseases, including type 2 diabetes and cervical disc disorders. Moreover, new associations such as low back pain and ovarian cancer were discovered.

Conclusion: These findings challenge the conventional notion of FFM as a protective factor in health, suggesting that higher FFM levels may be linked to an increased risk of various diseases. Further clinical studies are warranted to validate these findings and elucidate the underlying mechanisms.

Background: Diuretic resistance is commonly reported in acute heart failure (AHF), especially in patients presenting with impaired kidney function. Effective treatment strategies for promoting decongestion in this population remain unclear.

Methods: A systematic review using MEDLINE/Cochrane databases was performed from inception to January 2024, identifying randomized clinical trials (RCTs) including patients with diuretic resistance or at risk of diuretic resistance based on the presence of kidney dysfunction at study enrollment. Trials testing different pharmacological or invasive modalities compared to standard of care, placebo or an active comparator were considered. Data on decongestion-related outcomes, safety outcomes, and clinical outcomes up to 90 days were collected.

Results: Among the 22 RCTs included, 6 trials involved 529 patients with established diuretic resistance, while 16 trials enrolled 1,913 patients at risk of diuretic resistance. Diuretic resistance was differently defined across studies and most trials focused on interventions targeting different sites of action along the renal tubules. The different treatment strategies demonstrated efficacy in promoting decongestion while being associated with a mild increase in creatinine and cystatin C. The use of appropriately high doses of intravenous loop diuretics was able to promote decongestion across the spectrum of kidney dysfunction. The presence of baseline kidney dysfunction did not identify a population resistant to standard decongestive strategies.

Conclusions: Diuretic resistance is not accurately defined in AHF but is uncommon in patients treated with appropriately high doses of intravenous loop diuretics. The main therapeutic goal in the acute setting should focus on promoting decongestion instead of overemphasizing on mild changes in kidney-related biomarkers.

Introduction: Due to the typical exclusion of very elderly patients from clinical trials, the applicability of trial results to this population with heart failure remains uncertain. Limited data exist regarding the efficacy and safety of ultrafiltration in elderly patients with type 1 cardiorenal syndrome (CRS). Consequently, our study aimed to compare the efficacy and safety of ultrafiltration versus diuretics, providing evidence-based insights into the optimal management strategy for elderly patients with type 1 CRS.

Methods: In this prospective pilot trial, patients aged over 70 years old with type I CRS were treated with either diuretics or ultrafiltration. All patients were followed for up to 180 days post-discharge. Efficacy outcomes encompassed both immediate measures (changes in weight and dyspnea score from baseline to 48 h posttreatment) and long-term stability indicators (length of hospital stay and heart failure-related medical visits within 180 days post-discharge). Safety outcomes were assessed in both groups, focusing on changes in systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium, and sodium ion concentrations, bleeding or thromboembolic events, and major adverse cardiovascular events.

Results: A total of 159 patients with type I CRS were enrolled, with 80 receiving diuretics and 79 undergoing ultrafiltration. The mean age was 82.1 ± 5.8 years. At 48 h, patients in the ultrafiltration group demonstrated significantly greater weight loss and improvements in dyspnea score compared to those in the diuretic group (p < 0.05). Furthermore, the ultrafiltration group had shorter hospital stays and fewer medical visits for heart failure within 180 days post-discharge (p < 0.05). Notably, there were no statistically significant differences in safety outcomes between the two groups, indicating comparable safety profiles.

Conclusion: Ultrafiltration demonstrated superior efficacy with comparable safety profiles compared to diuretics. Therefore, ultrafiltration may be considered a preferred treatment option for elderly patients with type I CRS.

Background: Renal sodium avidity is a defining characteristic of chronic cardiorenal syndrome (CRS), leading to persistent sodium retention despite significant fluid overload. This phenomenon exacerbates volume overload, contributes to hemodynamic instability, and accelerates the decline of cardiac and renal function. Conventional diuretic therapies, though effective in acute settings, often fail chronically due to neurohormonal activation, renal tubular adaptations, and diuretic resistance.

Summary: This review explores innovative approaches to overcoming natriuresis and diuresis resistance in CRS patients. Emerging pharmacological treatments, including sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists, show potential in enhancing sodium excretion. Additionally, extracorporeal techniques such as ultrafiltration (UF) via hemodialysis and peritoneal dialysis (PD) provide precise sodium and fluid removal, bypassing many of the limitations of traditional pharmacotherapy. PD, in particular, has demonstrated efficacy in refractory cases by preserving residual renal function and improving diuretic responsiveness. As the saying goes, "there's always more than one way to skin a cat."

Key messages: (1) Renal sodium avidity plays a crucial role in CRS progression, necessitating targeted interventions. (2) Standard diuretic therapies often fail to provide sustained relief due to compensatory mechanisms. (3) Novel pharmacological agents (SGLT2 inhibitors, GLP-1R agonists) and extracorporeal techniques (UF, PD) offer promising alternatives for managing sodium retention and fluid overload. (4) A multidisciplinary and personalized treatment strategy is essential for optimizing patient outcomes and improving quality of life.

Introduction: Previous studies have reported a significant relationship between the baseline Chinese visceral adipose index (CVAI) and the risk of new-onset hypertension (NOH). However, the long-term effect of the CVAI and the risk of NOH remains uncertain. This study aimed to investigate the association between the cumulative CVAI and the risk of NOH.

Methods: Data were obtained from the China Health and Retirement Longitudinal Study from 2011 to 2020. In total, 2,836 Chinese participants ≥45 years were included. Multivariable logistic regression analysis as well as restricted cubic spline regression analysis were performed to assess the association of the cumulative CVAI, visceral adiposity index (VAI), and lipid accumulation product (LAP) with the risk of NOH. Furthermore, receiver operating characteristic (ROC) curve analysis was used to determine the area under the ROC curves between the risk of NOH and the adiposity indices to compare the predictive powers of the cumulative CVAI, VAI, and LAP for NOH.

Results: During the 5-year follow-up period, 433 cases of NOH were recorded. The cumulative CVAI, VAI, and LAP were positively associated with the risk of NOH. After adjusting for potential confounders, as compared to the lowest quartile of the cumulative CVAI, VAI, and LAP, the participants in the highest quartile had a significantly higher risk for NOH (odds ratio = 1.74, 1.46, and 1.95; 95% confidence interval = 1.25-2.42, 1.05-2.03, and 1.39-2.75, respectively). ROC analysis revealed that the cumulative CVAI had the highest relationship with the risk of NOH.

Conclusion: The cumulative CVAI was positively associated with an increased risk of NOH in middle-aged and elderly Chinese populations. In addition, the performance of the cumulative CVAI to predict NOH was superior to other visceral obesity indices. Monitoring long-term changes to the CVAI may assist with early identification of individuals at high risk of NOH.

Introduction: Haemodialysis (HD) is a life-sustaining treatment for individuals with end-stage kidney disease. However, the risk of mortality remains significantly higher compared to the general population, even when matched for age and sex. Global longitudinal strain (GLS), derived from speckle tracking echocardiography, has shown promise as a predictor of mortality in HD patients. However, its prognostic utility in patients with multiple cardiovascular risk factors such as diabetes mellitus (DM) and receiving HD remains unclear. This study aimed to evaluate the prognostic value of GLS in HD patients, with and without DM.

Methods: This prospective study was a long-term follow-up extension study of an earlier published study that investigated a cohort of HD patients from a single centre with a comprehensive cardiovascular imaging protocol. All patients had an echocardiography with the use of speckle tracking software to determine GLS. Patients were divided into group A (with DM) and group B (without DM). Patients were followed up until death, major adverse cardiovascular events, transplantation, or the censoring date (29 February 2024). Statistical analyses were performed using univariate and multivariate Cox proportional hazards models.

Results: A total of 184 patients receiving HD were included in the analysis. Patients with DM (group A) had significantly higher all-cause mortality (ACM) (47.1% vs. 20.7%, p < 0.001) and a lower chance of receiving a kidney transplant (13.2% vs. 43.1%, p < 0.001). In group A, GLS did not predict ACM, whereas in group B, a GLS cut-off of -15.76% correlated with higher 5-year ACM (p = 0.036). Left ventricular ejection fraction (LVEF) was a significant predictor of ACM in group A (HR 0.98; p = 0.036).

Conclusion: GLS is a poor predictor of adverse outcomes in HD patients with DM, likely due to their high cardiovascular risk. In contrast, GLS was a significant predictor of mortality in non-diabetic HD patients. LVEF may be a more reliable prognostic indicator in high-risk diabetic patients.

Background: The complex relationship between heart and kidney dysfunction has been a subject of medical inquiry since the 19th century. The term "cardio-renal syndrome" (CRS) was introduced in the early 2000s and has since become a focal point of research. CRS is typically categorized into five subtypes based on the sequence of cardiovascular and kidney disease events.

Summary: The cardiovascular-kidney-metabolic (CKM) syndrome, as defined by the American Heart Association, describes a set of interrelated metabolic risk factors and their effects on the kidneys and cardiovascular system. This syndrome emphasizes the complexity of managing patients with combined conditions and identifies several knowledge gaps, including disease mechanisms, clinical phenotype variability, and the impact of social determinants of health. The chronic cardiovascular-kidney disorder (CCKD) framework proposes a shift from the term "syndrome" to "disorder," focusing on concurrent cardiovascular and kidney problems regardless of their sequence.

Key messages: (i) The CCKD concept calls for simplification and conceptual clarity, arguing that understanding the bidirectional acceleration of disease progression between heart and kidney dysfunction can lead to more effective treatment strategies. (ii) Both CKM and CCKD share common pathophysiological mechanisms and risk factors, including hypertension, diabetes, obesity, and dyslipidemia. Managing these conditions requires a comprehensive approach that addresses the underlying risk factors and pathophysiological mechanisms. (iii) Future directions include embracing precision medicine, public health strategies, interdisciplinary care models, and ongoing research and innovation. Both frameworks underscore the need for comprehensive, interdisciplinary care models and innovative treatment strategies to address the complex interplay between cardiovascular and kidney diseases.

Background: Patients with chronic kidney disease (CKD) have an increased cardiovascular (CV) risk. The lower the glomerular filtration rate, the higher the CV risk.

Summary: Current data suggest that several uremic toxins lead to vascular inflammation and oxidative stress that, in turn, lead to endothelial dysfunction, changes in smooth muscle cells' phenotype, and increased degradation of elastin and collagen fibers. These processes lead to both functional and structural arterial stiffening and explain part of the increased risk of acute myocardial infarction and stroke reported in patients with CKD. Considering that, at least in patients with end-stage kidney disease, the reduction of arterial stiffness is associated with a parallel decrease of the CV risk; vascular function is a potential target for therapy to reduce the CV risk.

Key messages: In this review, we explore mechanisms of vascular dysfunction in CKD, paying particular attention to inflammation, reporting current data in other models of mild and severe inflammation, and discussing the vascular effect of several drugs currently used in nephrology.