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Background: The Cardiovascular-kidney-metabolic (CKM) syndrome, a concept recently proposed by the American Heart Association (AHA), highlights the intricate connection between metabolic, renal, and cardiovascular illnesses. Furthermore, the Atherogenic Index of Plasma (AIP), a useful biomarker for evaluating the risk of Cardiovascular Diseases (CVDs), has been associated with the risk of Adverse Cardiovascular Events (ACEs). Nonetheless, its precise function in populations in CKM syndrome Stages 0-3 remains unknown., Methods: This prospective study analyzed the data of 7,708 eligible participants (aged ≥ 45 years) from the Chinese Longitudinal Research of Ageing (CHARLS), particularly the 2011-2012 baseline survey (Wave 1). The primary exposure variable was AIP-a natural logarithm of the ratio of Triglycerides (TGs) to High-Density Lipoprotein Cholesterol (HDL-C). On the other hand, the primary endpoint was CVD incidence, which was determined based on self-reported past diagnoses. The relationship between AIP and CVD risk in the population in CKM syndrome stages 0-3 was examined using a Cox proportional risk model. Subgroup and mediation analyses were performed to further elucidate the interactions among these factors., Results: This study involved 7,708 participants in the CKM syndrome stages 0-3 [Mean age = 58.00 years; Interquartile Range (IQR) = 52.00-65.00 years]. The risk of developing CVD increased significantly with higher AIP levels. Specifically, the risk ratio for each unit increase in AIP was 1.31 (95% CI 1.11-1.55), while the Hazard Ratio (HR) for the group with the highest AIP levels compared to the group with the lowest AIP levels was 1.22 (95% CI 1.08-1.39). Mediation analysis revealed that metabolic syndrome accounted for 12.3% of the association between AIP levels and CVD risk (p = 0.024), highlighting its significance in CVD risk assessment., Conclusion: Herein, AIP levels correlated significantly positively with CVD risk in individuals in CKM stages 0-3, with metabolic syndrome as a key mediating factor. These findings suggest that AIP levels could be valuable not only for CVD risk assessment but also for clinical screening., Competing Interests: Declarations. Ethical approval: The research was approved by the Peking University Institutional Review Board and carried out in compliance with the ethical standards outlined in the Declaration of Helsinki. Field personnel performed standardized, verified interviews in compliance with the Declaration of Helsinki’s ethical norms and with approval from the Peking University Institutional Review Board, and all participants gave their informed permission. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: As an emerging concept, Cardiovascular-kidney-metabolic syndrome (CKM) elucidates the intricate interconnection between metabolic disorders(Mets), cardiovascular disease(CVD), and chronic kidney disease(CKD). Within this context, while numerous studies have demonstrated a correlation between the Atherogenic Index of Plasma (AIP) and CVD, the precise relationship between long-term fluctuations in the AIP and the incidence of CVD in patients with CKM syndrome remains unclear., Method: The CKM stages 0-3 population was obtained from the China Health and Retirement Longitudinal Study (CHARLS). The outcome CVD was defined as self-reported heart disease and/or stroke. AIP control level was classified using k-mean cluster analysis. Logistic regression was used to analyse the effect of cumulative AIP (cumAIP) on the incidence of CVD. Restricted cubic spline models (RCS) were used to explore the potential non-linear relationship between cumulative AIP and CVD risk at different CKM syndrome stages., Results: Of the 3429 CKM stages 0-3 participants, 620 patients developed CVD during the 3-year follow-up period. After adjusting for various confounders, the odds ratio (OR) for the well-controlled class 2 compared with the best AIP control class 1 were 1.37 (1.04, 1.81), the OR for the moderately-controlled class 3 were 1.54 (95% CI, 1.04-2.26), the poorly-controlled class 4 were 1.65 (95% CI, 1.13-2.41), and the worst-controlled class 5 were 2.14 (95% CI, 1.15-3.97). In restricted cubic spline regression analyses, changes in AIP were linearly associated with the occurrence of CVD events. Further weighted quartiles and regression analyses indicated that triglyceride(TG) was a key variable for AIP in predicting CVD events in the CKM stages 0-3 population., Conclusions: Poor control level of AIP are associated with an increased risk of CVD events in the population of CKM stages 0-3. Long-term dynamic monitoring of changes in AIP may help in the early identification of patients at high risk of developing CVD in the individuals with CKM stages 0-3., Competing Interests: Declarations. Ethical approval and consent to participate: The studies involving human participants were reviewed and approved by the Ethics Review Committee of Peking University. The patients/participants provided their written informed consent to participate in this study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States., Methods: We analyzed nationally representative National Health and Nutrition Examination Survey 1988 to 2018 data collected from 33 868 US adults (aged ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined the sex-specific prevalence of CKM syndrome and sex-specific CKM associations with all-cause mortality., Results: Of the 33 868 adults studied, the mean±SD age was 48.4±18.3 years with 52% women and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent stage 3 CKM seen for men (from 18.9% to 22.4%) compared with women (from 13.9% to 15.2%). Over a median follow-up of 13.3 years, there were 8745 deaths. In the multivariable Cox regression analysis, worsening CKM severity was associated with all-cause mortality ( P <0.001 for both sexes), with greater magnitudes of risk seen in women (hazards ratio, 1.24-3.33) compared with men (hazards ratio, 0.85-2.60) across all stages (likelihood ratio test χ 2 , 19.0; P interaction <0.001); results were similar for cardiovascular mortality (likelihood ratio test χ 2 , 22.3; P interaction <0.001)., Conclusions: Women, compared with men, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multisystem CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, kidney, and metabolic system pathophysiology to close a potentially widening sex disparities gap in multiorgan disease risk., Competing Interests: None.

Background: There is little research on cardiorenal anemia syndrome (CRAS) in China. This study was to describe the characteristics of patients with CRAS and to explore risk factors of all-cause death., Methods: A total of 81,795 patients were hospitalized from August 2012 to August 2021 in the nephrology department and cardiology department, of which 820 patients with CRAS were recruited into this study. The 820 patients were divided into three groups based on New York Heart Association (NYHA) functional class: a NYHA Class II group (n = 124), a NYHA Class III group (n = 492), and a NYHA Class IV group (n = 204). Demographics and laboratory tests were collected and risk factors of all-cause death were analyzed. The primary endpoint of the study was all-cause death., Results: 820 patients were included, with a median age of 65.00 (51.00-75.00) years and 61.2% were men. The median follow-up was 27.0 (13.0-51.0) months. 416 (50.7%) patients died during follow-up. Age, smoking history, cerebral infarction, NYHA functional class, albumin, serum creatinine (SCr), left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) remained independent predictors of all-cause mortality risk in patients with CRAS (P < 0.05) after adjusting to the potential confounders., Conclusions: In patients with CRAS, older age, smoking history, and more advanced systolic heart failure and renal failure correlated with worse clinical outcomes at follow-up., Competing Interests: Declarations. Ethical approval and informed consent: This study was approved by the ethics committee of Northern Jiangsu People’s Hospital (No. 2022ky310) and was carried out following the principle of the Helsinki Declaration. This is a retrospective study using de-identified data, and our institutional review board did not require consent from the patient. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A recent presidential advisory from the American Heart Association (AHA) has introduced the term cardiovascular-kidney-metabolic (CKM) syndrome to describe the complex interplay among health conditions linking heart, kidney, and metabolism. The aim of our study was to compare the prevalence of concurrent CKM syndrome components before and during the COVID-19 pandemic and identify associated risk factors. We conducted a study utilizing data from a real-world population obtained from a primary care database. The study cohort comprised a closed group followed over a 6-year period (2017-2022). A total of 81,051 individuals were included: 32,650 in the pre-pandemic period and 48,401 in the 2020-2022 triennium. After propensity-score matching for sex, age, and BMI, the study included 30,511 participants for each period. 3554 individuals were diagnosed with type 2 diabetes in the pre-pandemic period, compared to 7430 during the pandemic. Hypertension, dyslipidemia, and obesity displayed significant increases in prevalence during the pandemic, and prediabetes had a particularly sharp rise of 170%. Age-stratified analyses revealed a higher burden of CKM conditions with advancing age. Our findings indicate a substantial increase in the prevalence of CKM syndrome during the COVID-19 pandemic, with nearly half of the patients exhibiting one or more CKM syndrome components., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cardiorenal syndrome (CRS) refers to concomitant dysfunction of both the heart and kidneys. The pathology in CRS is bidirectional. Many individuals with kidney disease will develop cardiovascular complications. Conversely, rates of acute kidney injury and chronic kidney disease are high in cardiac patients. While our understanding of CRS has greatly increased over the past 15 years, most research has occurred in adult populations. Improving cardiorenal outcomes in children and adolescents requires increased collaboration and research that spans organ systems. The purpose of this review is to discuss key features of CRS and help bring to light future opportunities for pediatric-specific research., Competing Interests: Declarations. Conflicts of interest: The authors declare no competing interests. Disclosure: DB has nothing to disclose., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction and Aims: Fabry disease (FD) causes glycosphingolipid accumulation in the vascular endothelium, with predominantly cardiac and renal involvement. Its prevalence in patients with concomitant involvement of these two organs is unknown. The objective of the study was to determine the prevalence of FD in patients with left ventricular hypertrophy and any degree of chronic kidney disease., Patients and Methods: Patients with ventricular thickness ≥13mm and kidney disease from 29 Spanish hospitals were included. Sociodemographic variables and target organ involvement of FD were collected. Laboratory determinations of EF were carried out, with an enzymatic activity test±genetic test in men and direct genetic test in women., Results: Eight hundred ninety-eight patients with left ventricular hypertrophy and chronic kidney disease were included. The presence of heart failure and cardiorenal syndrome was common (46.1% and 40.1%). Three patients (2 men and 1 woman) were diagnosed with FD, based on the presence of a pathogenic variant in the GLA gene and classic signs of FD, resulting in a prevalence of 0.33% (CI 95% 0.06-1%). Six patients (0.66%) presented genetic variants of unknown significance, without showing classic signs of FD, while in 13 patients (3.2%) performing the blood test was impossible., Conclusions: FD is an important cause of left ventricular hypertrophy and chronic kidney disease. Genetic diagnosis is crucial for avoiding biases and ensuring accurate identification of FD, especially in women. The results support the inclusion of this disease in the differential diagnosis of patients with ventricular hypertrophy ≥13mm and chronic kidney disease., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

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., (© 2024. The Author(s).)

Importance: Cardiovascular-kidney-metabolic (CKM) syndrome-a novel, multistage, multisystem disorder as defined by the American Heart Association-is highly prevalent in the US. However, the prevalence of CKM stages by social determinants of health (SDOH) remains unclear., Objective: To investigate whether the prevalence of CKM stages varies by SDOH in US adults., Design, Setting, and Participants: This cross-sectional study used data from the National Health and Nutrition Examination Survey (1999-2018) and included a nationally representative sample of adults aged 30 to 79 years through complex, multistage probability sampling. Data were analyzed from April 1 to June 15, 2024., Exposures: The exposures included 5 CKM stages (ie, stages 0-4) reflecting progressive pathophysiology, with advanced (stages 3 or 4) and nonadvanced (stages 0, 1, or 2) disease. CKM stages were defined based on risk factors for metabolic syndrome, cardiovascular disease, and chronic kidney disease., Main Outcome and Measures: The main outcome was the age-standardized prevalence of CKM stages and advanced CKM stages across SDOH, including education, marital status, family income, food security, health insurance, employment, home ownership, and health care access., Results: Among 29 722 participants (weighted mean [SE] age, 50.8 [0.1] years; weighted 50.7% male), the age-standardized prevalence of CKM stages 0 to 4 was 13.6% (95% CI, 13.0%-14.3%), 29.9% (95% CI, 29.1%-30.7%), 43.7% (95% CI, 42.9%-44.5%), 4.7% (95% CI, 4.4%-5.0%), and 8.1% (95% CI, 7.6%-8.5%), respectively. Significant differences were observed in the prevalence of CKM stages across all unfavorable SDOH of interest compared with their favorable counterparts, with unemployment (18.8% [95% CI, 17.7%-20.1%] vs 11.4% [95% CI, 11.0%-11.9%]), low family income (16.1% [95% CI, 15.4%-16.8%] vs 10.1% [95% CI, 9.5%-10.7%]), and food insecurity (18.3% [95% CI, 17.1%-19.6%] vs 11.7% [95% CI, 11.2%-12.2%]) associated with an increased likelihood of advanced CKM stages. Participants with 2 or more unfavorable SDOH were more likely to have advanced CKM stages (age-standardized prevalence, 15.8% [95% CI, 15.2%-16.5%] vs 10.5% [95% CI, 9.9%-11.1%] with <2 unfavorable SDOH). Living in a rented home (15.9% [95% CI, 14.7%-17.0%] vs 9.3% [95% CI, 8.7%-9.9%] owning the home) or not living with a partner (13.2% [95% CI, 12.3%-14.3%] vs 9.2% [95% CI, 8.5%-9.8%] living with a partner) increased the likelihood of advanced CKM stages in female but not male participants., Conclusions and Relevance: In this cross-sectional study, disparities in the prevalence of CKM stages by SDOH, particularly family income, food security, and employment, with notable sex differences, were observed in US adults. These findings highlight the need to address inequities in CKM syndrome through targeted interventions.

The knowledge about the pathophysiology of cardiorenal syndrome has evolved remarkably over the past two decades. However, cardiorenal syndrome is only one subject within a much broader field of nephrocardiology, which encompasses the interconnection between nephrology and cardiovascular medicine from nine different standpoints of pathophysiology, epidemiology, prevention, prognosis, diagnosis, therapy, monitoring, risk factors and systemic diseases. The complexities of these nine elements of the interaction between nephrology and cardiovascular medicine are not adequately addressed in either of those two fields of medicine. Nephrocardiology is an emerging field in medicine aiming at addressing those subtleties to improve prognosis and quality of life of a large and vulnerable patient population with combined cardiovascular and nephrology related conditions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author has served as the guest editor of a special issue of Cardiology Clinics by Elsevier and is the editor of an upcoming textbook of a relevant subject, ‘Principles and Practice of Nephrocardiology’, which will be published by Elsevier., (Copyright © 2024. Published by Elsevier Inc.)

The recent conceptualization of the cardiovascular-kidney-metabolic (CKM) syndrome by the American Heart Association (AHA) opens an opportunity for a multidisciplinary and lifelong approach in the risk stratification, early prevention, and treatment of the vicious circle generated by the interaction of cardiovascular, renal and metabolic risk factors and aggravated by the development of cardiovascular diseases (including their full spectrum: heart failure, atrial fibrillation, coronary heart disease, stroke, and peripheral arterial disease), chronic kidney disease or type 2 diabetes mellitus, with the excess or dysfunctional adiposity as the trigger. Three publications offer the rational basis of a conceptual decalogue and action plan and a new cardiovascular risk stratification equation since the age of 30 that includes measures of renal function/damage, among others, to promote effective cardiovascular, renal, and metabolic prevention. In Spain, we must leverage this momentum to adapt these new concepts to our reality with greater and improved collaboration between primary care and the specialties involved in CKM syndrome, including the formation of multidisciplinary units for the optimal management using a patient-centred approach., Competing Interests: Declaration of competing interest AC has received research grants from CSL Vifor and conference or consultancy fees from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Esteve, GSK, Novo Nordisk, Otsuka, Sanofi (Mexico) and Vifor Pharma. JJB has received fees from AstraZeneca, Novo Nordisk, Lilly, Esteve, CSL Vifor, Kyowa Kirin, Chiesi and Daichii-Sankyo. MM has received fees for collaboration in teaching, training and/or scientific guidance from Alexion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Vifor, Esteve, GSK, Janssen Cilag, Mundifarma and Novo Nordisk. SC has received conference fees from AstraZeneca, Novo Nordisk Roche and Chiesi. JCJ declares that he has received fees for sitting on advisory boards for Pfizer, Novartis and Travere; that the entity he works for (Federación Nacional de Asociaciones ALCER [National Federation of Associations for the Fight against Kidney Diseases]) has received income for his participation as a speaker from the following companies: AstraZeneca, Astellas, Bayer and Ipsen, on Steering Committees or Advisory Boards from the following companies: Pfizer, BMS, CSL Vifor, GSK, Ipsen and Novartis; and that said entity has also received contributions under the Patronage Law from the companies Astellas, AstraZeneca, Baxter, Bayer, Boehringer-Ingelheim, BMS, Chiesi, CSL Vifor, Diaverum, Fresenius Medical Care, GSK, Ipsen, Novartis, Palex, Pfizer and Sanofi. RA has received fees for continuing medical education activities from AstraZeneca, Boehringer-Ingelheim, Lilly, Bayer, CSL Vifor and Novo Nordisk, and has served on advisory boards for Boehringer-Ingelheim, AstraZeneca and Bayer. AO has received grants from Sanofi and fees for consultancy and lectures, as well as travel expenses from Adviccene, Alexion, Astellas, AstraZeneca, Amicus, Amgen, Boehringer Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Lilly, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma and Spafarma; in addition, he is Director of the UAM-AstraZeneca Chair of chronic kidney disease and electrolytes; and holds shares in Telara Farma., (Copyright © 2024 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Patients with diabetes mellitus (DM) are at risk for a higher incidence and severity of COVID-19, as well as its adverse outcomes, including post-Covid syndrome., Aim: to assess the incidence of cardiorenal complications in patients with type 1 and type 2 diabetes (T1DM/T2DM) who have had COVID-19, and to analyze the structure and severity of disorders according to examination data at the Diamobil mobile medical diagnostic and treatment center., Materials and Methods: a cohort of T1DM and T2DM patients examined in Diamobil (n=318), with a confirmed anamnesis of COVID-19 (n=236). The time interval between COVID-19 and the visit to Diamobil was 8.7/8.2 months for T1DM/T2DM. The parameters of the last visit before COVID-19 recorded in the Federal Register of Diabetes (FRD) were used as initial data., Results: Clinical characteristics of patients with T1DM/T2DM: age - 49.2/64.5 years, duration of DM - 22/11 years, proportion of women - 64/73%, respectively. After analysis the data from visits before and after COVID-19 there weren't statistically significant differences in HbA1c levels for both types of DM (before 9.0/8.3%; after 8.4/8.2%, respectively), there was the intensification of glucose lowering therapy (the proportion of patients with T2DM on 2 and 3 component therapy increased by 4.3% and 1.6%, the proportion of patients on insulin therapy by 16%). After COVID-19, there was a statistically significant decrease in glomerular filtration rate (GFR) in T1DM from 88.1 to 62 ml/min/1.73 m2; with T2DM from 74.7 to 54.1 ml/min/1.73 m2. When assessing acute diabetic complications, there was an increase in the frequency of coma in T1DM by 1.5 times, severe hypoglycemia in T1DM by 3 times, and in T2DM by 1.7 times. Analysis of the frequency of cardiorenal complications before and after COVID-19 showed a total increase of 8.5% in T1DM, by 13.2% in T2DM, of which myocardial infarction, ischemic heart disease, and CHF increased in T1DM in the range from 1.5 to 5 times, with T2DM by 1.3 times, the frequency of CKD with T1DM by 1.5 times, with T2DM by 5.6 times., Conclusion: There was a decline of kidney filtration function (decrease in GFR) and an increase in the frequency of cardiovascular complications in both types of diabetes in post-Covid period while patients achieved a stable HbA1c levels by intensifying therapy during the COVID-19 infection. This fact reflects combined damage to the kidney and cardiovascular system as a part of the post-Covid syndrome and determines a key set of measures for the development of preventive strategies.

Cardiovascular-kidney-metabolic (CKM) syndrome and chronic kidney disease (CKD) are two significant comorbidities affecting a large proportion of the general population with considerable crosstalk. In addition to substantial co-incidence of CKD and CKM syndrome in epidemiological studies, clinical and pre-clinical studies have identified similar pathophysiological pathways leading to both entities. Patients with CKM syndrome are more prone to develop acute kidney injury and CKD, while therapeutic alternatives and their success rates are considerably lower in such patient groups. Nevertheless, the association between CKM syndrome and CKD or ESKD is bidirectional rather than being a cause-effect relationship as patients with CKD are also prone to develop peripheral insulin resistance, high blood pressure, and dyslipidemia. Furthermore, such patients are less likely to receive kidney transplantation in addition to the higher allograft dysfunction risk. We hereby aim to evaluate the association in-between kidney diseases and CKM syndrome, including epidemiological data, pre-clinical studies with pathophysiological pathways, and potential therapeutic perspectives., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The American Heart Association (AHA) recently defined the cardiovascular-kidney-metabolic syndrome (CKM) as a new entity to address the complex interactions between heart, kidneys, and metabolism. The aim of this study was to assess the outcome impact of CKM syndrome in patients undergoing noncardiac surgery., Methods: This is a secondary analysis of a prospective international cohort study including patients aged ≥45 years with increased cardiovascular risk undergoing noncardiac surgery. Main exposure was CKM syndrome according to the AHA definition. The primary end point was a composite of major adverse cardiovascular events (MACE) 30 days after surgery. Secondary end points included all-cause mortality and non-MACE complications (Clavien-Dindo class ≥3)., Results: This analysis included 14,634 patients (60.8% male, mean age = 72±8 years). MACE occurred in 308 patients (2.1%), and 335 patients (2.3%) died. MACE incidence by CKM stage was as follows: CKM 0: 5/367 = 1.4% (95% confidence interval [CI], 0.4%-3.2%); CKM 1: 3/367 = 0.8% (95% CI, 0.2%-2.4%); CKM 2: 102/7440 = 1.4% (95% CI, 1.1%-1.7%); CKM 3: 27/953 = 2.8% (95% CI, 1.9%-4.1%); CKM 4a: 164/5357 = 3.1% (95% CI, 2.6%-3.6%); CKM 4b: 7/150 = 4.7% (95% CI, 1.9%-9.4%). In multivariate logistic regression, CKM stage ≥3 was independently associated with MACE, mortality, and non-MACE complications, respectively (MACE: OR 2.26 [95% CI, 1.78-2.87]; mortality: OR 1.42 [95% CI: 1.13 -1.78]; non-MACE complications: OR 1.11 [95% CI: 1.03-1.20])., Conclusion: The newly defined CKM syndrome is associated with increased morbidity and mortality after non-cardiac surgery. Thus, cardiovascular, renal, and metabolic disorders should be regarded in mutual context in this setting., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Poor cardiovascular-kidney-metabolic (CKM) health is associated with premature mortality and excess morbidity in the United States. Adverse social conditions have a prominent impact on cardiometabolic diseases during the life course. We aim to examine the association between social risk profile (SRP) and CKM multimorbidity among US adults., Methods and Results: We used data from the National Health and Nutrition Examination Survey from 1999 to 2018. The definition of CKM syndrome is the coexistence of subclinical or clinical cardiovascular disease, chronic kidney disease, and metabolic disorders. We classified participants by 4 CKM stages according to the different clinical severity of different forms of CKM syndrome. We calculated the summed number of positive SRP measures, including employed, high-income level, food secure, high education attainment, private insurance, owning a house, and married, as SRP scores and classified them into 4 levels by quartiles: low (0-2), lower-middle (3-4), upper-middle (5-6), and high (7-8). A total of 18 373 US adults, aged 20 to 79 years, were included in our analyses. There were 2567 (9.4%) participants with low SRP score level. Most individual SRP measures and a combined SRP score were associated with CKM stages. Compared with high SRP score level, low SRP level was associated with higher odds of having CKM stage 1 (odds ratio [OR], 1.34 [95% CI, 1.06-1.70]), CKM stage 2 (OR, 2.03 [95% CI, 1.59-2.58]), CKM stage 3 (OR, 5.28 [95% CI, 3.29-8.47]), and CKM stage 4 (OR, 5.97 [95% CI, 4.20-8.49])., Conclusions: Cumulative social disadvantage, denoted by higher SRP burden, was associated with higher odds of CKM multimorbidity, independent of demographic and lifestyle factors.

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.

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., 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., (Copyright: © Saudi Medical Journal.)

The association between cardiac and kidney dysfunction has received attention over the past two decades. A putatively unique syndrome, the cardiorenal syndrome, distinguishing five subtypes on the basis of the chronology of cardiac and kidney events, has been widely adopted. This review discusses the methodologic and practical problems inherent to the current classification of cardiorenal syndrome. The term "disorder" is more appropriate than the term "syndrome" to describe concomitant cardiovascular and kidney dysfunction and/or damage. Indeed, the term disorder designates a disruption induced by disease states to the normal function of organs or organ systems. We apply Occam's razor to the chronology-based construct to arrive at a simple definition on the basis of the coexistence of cardiovascular disease and CKD, the chronic cardiovascular-kidney disorder (CCKD). This conceptual framework builds upon the fact that cardiovascular and CKD share common risk factors and pathophysiologic mechanisms. Biological changes set in motion by kidney dysfunction accelerate cardiovascular disease progression and vice versa . Depending on various combinations of risk factors and precipitating conditions, patients with CCKD may present initially with cardiovascular disease or with hallmarks of CKD. Treatment targeting cardiovascular or kidney dysfunction may improve the outcomes of both. The portfolio of interventions targeting the kidney-cardiovascular continuum is in an expanding phase. In the medium term, applying the new omics sciences may unravel new therapeutic targets and further improve the therapy of CCKD. Trials based on cardiovascular and kidney composite end points are an attractive and growing area. Targeting pathways common to cardiovascular and kidney diseases will help prevent the adverse health effects of CCKD., (Copyright © 2023 by the American Society of Nephrology.)

Managing non-cardiac comorbidities in heart failure (HF) requires a tailored approach that addresses each patient's specific conditions and needs. Regular communication and coordination among healthcare providers is crucial to providing the best possible care for these patients. Poorly controlled hypertension contributes to left ventricular remodeling and diastolic dysfunction, emphasizing the importance of optimal blood pressure control while avoiding adverse effects. Among HF patients with diabetes, SGLT2 inhibitors and mineralocorticoid receptor antagonists have shown promise in reducing HF-related morbidity and mortality. Chronic kidney disease exacerbates HF and vice versa, forming the vicious cardiorenal syndrome, so disease-modifying therapies should be maintained in HF patients with comorbid CKD, even with transient changes in kidney function. Anemia in HF patients may be multifactorial, and there is growing evidence for the benefit of intravenous iron supplementation in HF patients with iron deficiency with or without anemia. Obesity, although a risk factor for HF, paradoxically offers a better prognosis once HF is established, though developing treatment strategies may improve symptoms and cardiac performance. In HF patients with stroke and atrial fibrillation, anticoagulation therapy is recommended. Among HF patients with sleep-disordered breathing, continuous positive airway pressure may improve sleep quality. Chronic obstructive pulmonary disease often coexists with HF, and many patients can tolerate cardioselective beta-blockers. Cancer patients with comorbid HF require careful consideration of cardiotoxicity risks associated with cancer therapies. Depression is underdiagnosed in HF patients and significantly impacts prognosis. Cognitive impairment is prevalent in HF patients and impacts their self-care and overall quality of life.

Background: Heart failure (HF) and kidney disease frequently co-occur, increasing mortality risk. The cardiorenal syndrome results from damage to either the heart or kidney impacting the other organ. The epidemiology of cardiorenal syndrome among the general population is incompletely characterized and despite shared risk factors with HF, differences in mortality risk across key demographics have not been well described. Thus, the primary goal of this study was to analyze annual trends in cardiorenal-related mortality, evaluate if these trends differed by age, sex, and race or ethnicity, and describe these trends against a backdrop of HF mortality., Methods and Findings: The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database was used to examine cardiorenal- and HF-related mortality in the US between 2011and 2020. International Classification of Diseases, 10 Revision codes were used to classify cardiorenal-related deaths (I13.x) and HF-related deaths (I11.0, I13.0, I13.2, and I50.x), among decedents aged 15 years or older. Decedents were further stratified by age group, sex, race, or ethnicity. Crude and age-adjusted mortality rates (AAMR) per 100,000 persons were calculated. A total of 97,135 cardiorenal-related deaths and 3,453,655 HF-related deaths occurred. Cardiorenal-related mortality (AAMR, 3.26; 95% CI: 3.23-3.28) was significantly lower than HF-related mortality (AAMR, 115.7; 95% CI: 115.6-115.8). The annual percent change (APC) was greater and increased over time for cardiorenal-related mortality (2011-2015: APC, 7.1%; 95% CI: 0.7-13.9%; 2015-2020: APC, 19.7%, 95% CI: 16.3-23.2%), whereas HF-related mortality also increased over that time period, but at a consistently lower rate (2011-2020: APC, 2.4%; 95% CI: 1.7-3.1%). Mortality was highest among older and male decedents for both causes. Cardiorenal-related deaths were more common in non-Hispanic or Latino Blacks compared to Whites, but similar rates were observed for HF-related mortality. A larger proportion of cardiorenal-related deaths, compared to HF-related deaths, listed cardiorenal syndrome as the underlying cause of death (67.0% vs. 1.2%)., Conclusions: HF-related deaths substantially outnumber cardiorenal-related deaths; however, cardiorenal-related deaths are increasing at an alarming rate with the highest burden among non-Hispanic or Latino Blacks. Continued surveillance of cardiorenal-related mortality trends is critical and future studies that contain detailed biomarker and social determinants of health information are needed to identify mechanisms underlying differences in mortality trends., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2024. The Author(s).)

The management of patients with complex comorbidity involving several organ systems can use an approach focused on each organ system independently or can use an approach trying to integrate various injuries and dysfunction into a single syndrome. Cardiorenal syndromes can develop with an initial injury to either the heart or kidney and then sequential involvement of the second organ. This can occur acutely or chronically. Cardiorenal syndrome type 3 is defined by acute renal injury with subsequent cardiac injury and/or dysfunction. Studies on these patients must use strict inclusion criteria. Pavan reported information on 100 patients with acute kidney injury in India to determine the frequency of cardiorenal syndrome type 3. He excluded patients with significant prior comorbidity. The most frequent causes of acute kidney injury in these patients were drug toxicity, gastroenteritis with volume contraction, and obstetrical complications. This study included 100 patients with acute kidney injury, and 29 developed cardiorenal syndrome type 3. Important outcomes included frequent mortality and chronic renal failure. Other studies have reported that cardiorenal syndrome type 3 occurs relatively infrequently. The analysis of large data bases has demonstrated that the development of acute kidney injury in hospitalized patients has important consequences, including the development of heart failure and increased mortality, but the complexity of these cohorts makes it difficult to determine the time course for the development of multisystem disorders. The pathogenesis of cardiorenal syndrome type 3 involves mitochondrial dysfunction, immune dysregulation, and ischemia-reperfusion. Cardiac events occur secondary to fluid overload, electrolyte disorders, and uremic toxins. These patients need increased attention during hospitalization and outpatient management in an effort to slow the progression of the primary disorder and treat complications., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiorenal anemia syndrome (CRAS) is a common complication among patients with heart failure and is associated with poor clinical outcomes. However, there is a paucity of published data concerning CRAS, despite of significant increase in heart failure patients attending medical services in developing countries. This study aims to assess the prevalence, clinical correlates, and outcomes of CRAS among patients with heart failure attending the Benjamin Mkapa Hospital in Dodoma, Tanzania., Methodology: A prospective observational study is ongoing at the Benjamin Mkapa Hospital in Dodoma, Tanzania. Currently, 92 patients have been recruited into this study and process is not yet completed. The socio-demographic data, clinical correlates, and prevalence of CRAS will be determined at baseline meanwhile, the outcomes of CRAS will be determined during a follow-up period of six months from the date of enrollment. CRAS is the primary outcome of the study. Data will be categorized into CRAS and non-CRAS during statistical analysis. Mean and standard deviation will be used for normally distributed continuous variables while median and interquartile range will be used for skewed data. Frequencies and percentages will summarize categorical variables. Clinical correlates and outcomes of CRAS will be analyzed and compared by using univariate and multivariate logistic regression and Cox proportional hazards models. A two-tailed p-value of less than 0.05 will indicate statistical significance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Edwin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The purpose of this paper is to analyses the cases with cardiorenal syndrome, and the ratio of cardiovascular disease and COVID-19. Prospective methods were used to conduct this research, including the period (January 2020-December 2021). Cases of patients treated at the Nephrology Clinic at the University Clinical Center of Kosovo (UCCK) have been studied. The categorical variables were analyzed with the X² test and the Fisher exact test. The study included 120 patients with acute renal disease treated at the Nephrology Clinic at the University Clinical Center of Kosovo (UCCK), of which 46 (38.3%) female and 74 (61.6%) male. Of the 120 patients included in the study 4 were 18-34 years old, 8 were 35-49 years old, 30 were 50-64 years old, and 78 were > 65 years old. There is a strong link between cardiorenal syndrome and age. Regarding cardiorenal syndrome and its association with other diseases in this prospective study were found these concomitant diseases such as: diabetes mellitus type 2, secondary anemia, hypothyroidism, hyperparathyroidism, pneumonia, sepsis, ascites, mesenteric tumor, hyperkalemia, and Covid-19 Infection. There is a strong link between cardiorenal syndrome and COVID-19 Infection. In recent decades various studies have been done against the definition of cardiorenal syndrome, the understanding of pathophysiology, the use of new biomarkers that represent a new dimension in the diagnostic algorithm, and the difficulties in treating this syndrome.

In the last 20 years, the cardiorenal syndrome (CRS) field has received growing attention. There have been innovations in cardiorenal interaction patterns, biological markers and management of CRS, and even significant changes in its concept and the paradigm of CRS pathophysiology, which considerably increases the difficulties in understanding and in-depth study of this field. However, few study summarized the development process of CRS and critical issues. This review focuses on topical evolutions and emerging trends in CRS pathophysiology, diagnostic pathways, and treatment strategies. A quantitative retrospective analysis, visual review, and evaluation of 1452 articles published in the domain of CRS from 2003 to 2022 was conducted using a bibliometric analysis based on the classic CiteSpace and VOSviewer software rather than a general review, aiming to provide reasonable ideas and directions for future research on CRS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The cardiometabolic syndrome focuses on the association between type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), whereas the cardiorenal syndrome focuses on the association between chronic kidney disease (CKD) and heart failure (HF). Consideration of these two syndromes as a single entity has not been well described. Methods: We used the electronic medical records of Kaiser Permanente Northwest to identify 387,985 members aged 18+ years with a serum creatinine measured from 2005 to 2017. If the estimated glomerular filtration rate was <60 mL/min per 1.73 m 2 , we required a second confirmatory measurement 3-12 months later. Patients were followed through 2019. We calculated the age- and gender-adjusted incidence and progression of CKD per 1000 person-years using generalized estimating equations. We used Cox proportional hazard models to assess the time-dependent effect of each condition on incidence of the other conditions. Results: CKD incidence rates were highest in patients with T2DM, ASCVD, and HF (27.0 per 1000 person-years [95% confidence interval (CI) 24.8-29.4] vs. 5.9 [5.8-6.0] in patients with none of these conditions). Similar results were obtained for CKD progression (309.0, 283.9-336.4 for all three conditions vs. 147.9, 143.3-152.4 for no condition). In time-dependent models, all three conditions were independently associated with CKD incidence, being highest for HF (hazard ratio 2.14, 95% CI 2.07-2.21). All relationships between CKD, T2DM, ASCVD, and HF were significant and bidirectional. Conclusions: The presence of CKD, T2DM, HF, and ASCVD each conveys risk on the others. A cardiometabolic renal syndrome comprising these conditions may be an important disease entity that requires a comprehensive treatment approach.

Purpose of the Work: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF., Findings: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m 2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Type 2 diabetes mellitus (T2DM) is a risk factor for cardiac and renal complications; its effect on cardiorenal syndromes is unknown., Methods: In a French nationwide cohort of 5,123,193 patients hospitalized in 2012 with ≥5 years of follow-up, we assessed the effect of T2DM on cardiorenal syndrome (CRS) (using cardiorenal, renocardiac, and simultaneous subtypes) incidence and outcomes using 1:1 propensity matching., Results: Among 4,605,236 adults without cardiorenal syndrome, 380,581 (8.5%) with T2DM were matched to 380,581 adults without T2DM. During follow-up, CRS occurred in 104,788 patients: simultaneous n = 25,225 (24.0%); cardiorenal n = 51,745 (49.4%); renocardiac n = 27,818 (26.5%). T2DM doubled the risk of incident CRS (1.30% versus 0.65%/year; adjusted hazard ratio (HR) for any cardiorenal syndrome: 2.14 [95% confidence interval 2.10;2.19]; renocardiac: 2.43 [2.34;2.53]; cardiorenal: 2.09 [2.03;2.15]; simultaneous: 1.94 [1.86;2.03]. Among the 26,396 adults with CRS in 2012, 11,355 (43.0%) had T2DM and were younger than non-diabetic adults (77.4 ± 9.5 versus 82.3 ± 10.0); 8,314 patients with T2DM were matched to 8,314 patients without. T2DM increased risk of: end-stage kidney disease, adjusted HR 1.50 [1.39;1.62]; myocardial infarction 1.35 [1.19;1.53]; cardiovascular death 1.20 [1.13;1.27]; heart failure 1.17 [1.12;1.21]; and all-cause death 1.09 [1.06;1.13], but not ischemic stroke., Conclusion: Patients with T2DM represent almost half of patients with CRS and are younger than their non-diabetic counterparts. T2DM doubles the risk of CRS and increases the risk of death, cardiovascular outcome, and end-stage kidney disease but not ischemic stroke after CRS., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort., Method: We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD)., Results: The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46, p = 0.002 ). In a subgroup analysis, there was significantly high mortality in the 0.26-0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23-1.82, p < 0.001 ). Thus, the p for trend was 0.013 . With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05-1.30, p = 0.004 ], especially in the > 0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01-1.41, p = 0.046; p for trend = 0.006 ). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63-0.99, p = 0.048 ). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16-1.54, p < 0.001 ). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26 - 0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06-1.66, p = 0.015 ; sHR = 1.44; 95% CI = 1.18-1.75; p for trend < 0.001 )., Conclusion: Digoxin should be prescribed with caution to patients with CRS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Kuo, Chang, Wang, Yang, Niu, Kuo, Chen, Wen, Hung, Chang and Lin.)

Background: Literature regarding outcomes of cardiorenal syndrome (CRS) among heart failure with reduced ejection fraction (HFrEF) is limited., Objective: To study the clinical outcomes and 30-day readmission rates of CRS patients with HFrEF., Methods: Data from the Nationwide Readmissions Database (NRD) that constitutes 49.1% of the stratified sample of all hospitals in the United States (US), representing >95% of the national population, was analyzed for the CRS with HFrEF visits from 2018 to 2019. CRS was defined by the ICD-10 codes., Results: Out of the 1,530,749 index CRS-related hospitalizations (mean age:64.37 ± 13.30 years; 38.6%females) 73,126 (6.0%) CKD I-II, 883,119 (72.6%) CKD III-IV, and 258,835 (21.3%) CKD V-and-more related encounters were recorded. Mortality was higher among CKD stage V-and-more in comparison to other subgroups(7.6%vs5.73%;p < 0.001). AKI with underlying CKD was more common among stage III-IV compared to other subgroups (55.9%vs43.7%;p < 0.001). Respiratory failure, the second major complication, was more common among stage V-and-more compared to other subgroups (32.5%vs30%;p < 0.001). The overall CRS-related 30-day readmission rate was 22.7%, with CKD V-and-more accounting for highest rates(29.89%), followed by CKD stage III-IV(20.05%) and CKD I-II(12.99%). The primary etiology for 30-day readmission was cardiovascular among all subgroups (54.2%, 54.6%, and 41.80%, which corresponds to CKD I-II, CKD III-IV and CKD V-and-more, respectively)., Conclusion: CRS among HFrEF accounts for substantial healthcare burden with high 30-day readmission rates. Higher all-cause mortality and 30-day readmissions were associated with worse renal disease. This would suggest that more vigilance is needed by physicians for discharge planning among this patient population., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cardiorenal syndromes (CRSs) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown., Methods: The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5 123 193 patients who were admitted in a French hospital in 2012)., Results: Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence), while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%).The incidence of major outcomes was 57.3%, 53.0%, 79.2% for death; 18.8%, 10.9%, 27.5% for cardiovascular death; 52.6%, 34.7%, 64.3% for HF; 6.2%, 5.5%, 5.6% for myocardial infarction (MI); 6.1%, 5.8%, 5.3% for ischaemic stroke; and 23.1%, 4.8%, 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively.As compared with isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischaemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared with isolated CKD, the risk of ESKD was similar for cardiorenal CRS only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5 123 193 patients)., Conclusions: The additional impact of CRS versus isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background and Aim: In cardiorenal syndrome (CRS) type 1, acute cardiac failure or acute decompensation of chronic heart failure causes acute kidney injury (AKI). Every individual AKI episode increases the risk for chronic kidney disease (CKD) in the long term. In this study, we aimed to evaluate epidemiological characteristics and outcome variables of CRS type 1 individuals from the nephrologist's perspective., Methods: The study was performed in a retrospective, observational manner. All AKI patients treated at the Brandenburg Hospital of the Medical School of Brandenburg between January and December 2019 were screened for diagnostic criteria of CRS type 1. Endpoints were in-hospital death, need for dialysis, and renal recovery., Results: During the screening, 198 out of 1189 (16.6%) AKI subjects were assigned to the diagnosis CRS type 1. The overall in-hospital mortality was 19.2%; 9.6% of the patients required dialysis due to AKI. Complete recovery of kidney function was observed in 86 individuals (43.4%); incomplete recovery occurred in 55 patients (27.8%). Mortality-predictive variables were AKIN stage 2, longer ICU treatment, and insulin-dependent diabetes. Regarding dialysis, AKIN stage 3 and higher potassium at the time of diagnosis were predictive. Subjects with longer in-hospital stay recovered more often from CRS type 1., Conclusions: The incidence of CRS type 1 is high (∼16% of all in-hospital AKI subjects) and the mortality is higher than the average mortality of AKI in general. At the same time, complete recovery of kidney function occurs less frequent. The kidney-related follow-up management of CRS type 1 needs to be significantly optimized to improve the long-term outcome of affected patients., (© 2021. The Author(s).)

The cardiorenal nexus encompasses a bidirectional relationship between the heart and the kidneys. Chronic abnormalities in cardiac function can lead to progressive kidney disease, and chronic kidney disease can lead to progressively decreasing cardiac function and increasing risk of cardiovascular disease, including heart failure. About 15% of US adults have chronic kidney disease, 2% have heart failure, and 9% have cardiovascular disease. Prevalence rates of chronic kidney disease, cardiovascular disease, and associated morbidities such as type 2 diabetes are expected to increase with an aging population. Observational studies provide evidence for the cardiorenal nexus. Follow-up data from placebo arms of clinical trials in chronic kidney disease or cardiovascular disease show higher rates of renal and cardiovascular outcome events in patient subgroups with type 2 diabetes than in those without type 2 diabetes. The cardiorenal syndromes develop along an interlinked pathophysiological trajectory that requires a holistic, collaborative approach involving a multidisciplinary team. There is now a compendium of treatment options. Greater understanding of the underlying pathophysiology of the cardiorenal nexus will support optimization of the management of these interlinked disease states.

Background: Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single-nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown., Methods and Results: This prospective cohort study included 2946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor., Conclusion: Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: Patients with end-stage renal disease (ESRD) often present with an increased risk of cardiovascular disease. Conditions of compromised cardiovascular health such as atrial fibrillation (AFIB) and peripheral arterial disease (PAD) may alter biomarker levels in a way that reflects worsening ESRD. This study profiled biomarkers and laboratory parameters of endothelium dysfunction in patients with ESRD, categorized by additional AFIB and PAD conditions., Methods: Citrated blood samples were collected from 95 patients with ESRD. Biomarker levels were measured from plasma samples using sandwich ELISAs, including tissue plasminogen activator (tPA), D-dimer, and nitrotyrosine. Lab parameters, including BUN, calcium, creatinine, parathyroid hormone, phosphate, alkaline phosphatase, ferritin, transferrin, and total iron capacity, and patient comorbidities were obtained from patient medical records. The comorbidities were determined through provider notes, and evidence of applicable testing., Results: 14.89% of patients were found to have atrial fibrillation (n = 14), 30.85% of patients were found to have peripheral arterial disease (n = 29), and 6.38% of patients were found to have both peripheral arterial disease and atrial fibrillation (n = 6). When compared to patients with only ESRD, patients with ESRD and PAD showed elevated levels of D-Dimer (p = .0314) and nitrotyrosine (p = .0330). When compared to patients with only ESRD, patients with atrial fibrillation showed elevated levels of D-Dimer (p = .0372), nitrotyrosine (p = .0322), and tPA (p = .0198)., Conclusion: When compared to patients with just ESRD, patients with concomitant PAD had elevated levels of Nitrotyrosine and D-dimer; while patients with concomitant Afib had elevated levels of nitrotyrosine, D-dimer, as well as tPA.

Aims: Whereas the combination of anaemia and chronic kidney disease (CKD) has been extensively studied in patients with heart failure (HF), the contribution of iron deficiency (ID) to this dysfunctional interplay is unknown. We aimed to assess clinical associates and pathophysiological pathways related to ID in this multimorbid syndrome., Methods and Results: We studied 2151 patients with HF from the BIOSTAT-CHF cohort. Patients were stratified based on ID (transferrin saturation <20%), anaemia (World Health Organization definition) and/or CKD (estimated glomerular filtration rate <60 ml/min/1.73 m 2 ). Patients were mainly men (73.3%), with a median age of 70.5 (interquartile range 61.4-78.1). ID was more prevalent than CKD and anaemia (63.3%, 47.2% and 35.6% respectively), with highest prevalence in those with concomitant CKD and anaemia (77.5% vs. 59.3%; p < 0.001). There was a considerable overlap in biomarkers and pathways between patients with isolated ID, anaemia or CKD, or in combination, with processes related to immunity, inflammation, cell survival and cancer amongst the common pathways. Key biomarkers shared between syndromes with ID included transferrin receptor, interleukin-6, fibroblast growth factor-23, and bone morphogenetic protein 6. Having ID, either alone or on top of anaemia and/or CKD, was associated with a lower overall summary Kansas City Cardiomyopathy Questionnaire score, an impaired 6-min walk test and increased incidence of hospitalizations and/or mortality in multivariable analyses (all p < 0.05)., Conclusion: Iron deficiency, CKD and/or anaemia in patients with HF have great overlap in biomarker profiles, suggesting common pathways associated with these syndromes. ID either alone or on top of CKD and anaemia is associated with worse quality of life, exercise capacity and prognosis of patients with worsening HF., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m 2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m 2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

The interactions and feedback mechanisms involved in heart and renal failure are more complex than previously thought and are grouped under the term "cardio-renal axis". In the last decades, it has always been emphasized that renal dysfunction in patients with heart failure can be attributed exclusively to low renal plasma flow resulting from reduced cardiac output. In the last two decades cardiorenal syndrome has been established to set complex and close interactions between heart and kidney. Cardiologists and nephrologist should interact in their daily clinical practice to provide better patients' management. In this review, we will point out main features of cardiorenal axis and cardiorenal syndrome to shift into specific sets of management in Italy starting by Guyton's hypothesis till present days., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Coexisting dysfunction of heart and kidney, the cardiorenal syndrome, is a common condition and is associated with worsening of outcomes and complexities of diagnostic, preventive, and therapeutic approaches. The knowledge of the physiology of heart and kidney and their interaction with each other and with other organ systems has progressed significantly in recent years, resulting in a better understanding of the pathogenesis of cardiorenal syndrome. A robust knowledge of the pathophysiology and of the latest practical advancements about cardiorenal syndrome is necessary for cardiologists, nephrologists, and other practitioners who provide medical care to the patients with heart and kidney diseases., Competing Interests: Disclosure The author has no conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Type 1 cardiorenal syndrome is associated with higher mortality in heart failure patients. However, few studies have compared the diagnostic criteria of acute kidney injury (AKI) in this population., Objective: To assess clinical and functional features and factors associated AKI in patients with heart failure., Method: Retrospective, cohort study on patients with decompensated heart failure or recent acute myocardial infarction, conducted in a tertiary hospital in a low-income region of Brazil. Clinical, laboratory and echocardiographic features were compared between patients with and without AKI according to the Acute Kidney Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The level of statistical significance was set at p < 0.05., Results: Of 81 patients, 61.73% had AKI. Mean creatinine and urea levels were 1.79±1.0 mg/dL and 81.5±46.0 mg/dL, respectively, and higher in the group with AKI (p < 0.05). No evidence of a relationship between cardiac changes and reduced renal function. Chronic renal disease was associated with higher prevalence of AKI. Higher mortality was observed in patients with AKI than in patients without AKI (32.0% vs. 9.8%, p = 0.04, OR 8.187 ad 95% confidence interval 1.402-17.190, p = 0.020)., Conclusion: In this population of patients with heart failure, AKI was highly prevalent and considered an independent risk factor for mortality. Cardiac changes were not associated with AKI, and the KDIGO and AKIN criteria showed similar performance.

Aims and Objectives: To study the incidence,risk factors and in hospital mortality of Type I Cardiorenal syndrome(CRS1). To study the incidence of hyperkalemia in patients receiving Acei, ARB's or MRA Materials and Methods: Prospective observational cohort study done between June and December 2015 in Madras Medical Mission, Chennai. Consecutive patients admitted with ACS/ADHF were studied and clinical, biochemical and laboratory data was collected. The development of CRS1 was determined by KDIGO criteria. Statistical analysis was done using IBM SPSS version 21., Results: Among 460 patients studied, 153 (34%) developed CRS 1 according to KDIGO criteria. The number of diabetics and patients with pre-existing CKD was significantly higher in the CRS 1 group (p=0.00). Mortality was significantly higher in the CRS 1 group (20.2% vs. 7.8% p=0.00). The presence of CKD, Diabetes mellitus, inotropic requirement and eGFR, 60 ml/min/1.73 m2 were significant predictors of CRS 1. Among patients with CRS1, 55 patients (23.5%) needed renal replacement therapy (15.6 % acute peritoneal dialysis, 20.2% SLED). There was no significant difference in the incidence of hyperkalemia in patients who were on prior Acei, ARBs and MRA., Conclusion: There is a high incidence of CRS 1 in our setting and the mortality is significantly higher in this group of patients. Early nephrology referral and prompt stoppage of nephrotoxic agents can significantly reduce the incidence and risk of CRS1., (© Journal of the Association of Physicians of India 2011.)

Cardiorenal syndrome (CRS) describes a specific acute and chronic clinical picture in which the heart or the kidney are primarily dysfunctioning and secondarily affect each other. CRS is divided into five classes: acute and chronic CRS, acute and chronic renocardiac syndromes, and secondary dysfunction of heart and kidneys. This article specifically details the classification and the epidemiology, some risk factors, and the pathophysiology of CRS. Some emerging aspects of CRS are also discussed, such as CRS in patients with end-stage heart failure, with mechanical ventricular assistance, and after heart transplantation. Finally, some aspects of pediatric CRS are detailed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.

Background: Hyponatremia is known to be associated with a worse patient outcome in heart failure. In cardiorenal syndrome (CRS), the prognostic role of concomitant hyponatremia is unclear. We sought to evaluate potential risk factors for hyponatremia in patients with CRS presenting with or without hyponatremia on hospital admission., Methods: In a retrospective study, we investigated 262 CRS patients without sepsis admitted to the University Hospital Halle over a course of 4 years. CRS diagnosis was derived from an electronic search of concomitant diagnoses of acute or chronic (NYHA 3-4) heart failure and acute kidney injury (AKIN 1-3) or chronic kidney disease (KDIGO G3-G5 nonD ). A verification of CRS diagnosis was done based on patient records. Depending on the presence (Na < 135 mmol/L) or absence (Na ≥ 135 mmol/L) of hyponatremia on admission, the CRS patients were analyzed for comorbidities such as diabetes, presence of hypovolemia on admission, need for renal replacement therapy and prognostic factors such as in-hospital and one-year mortality., Results: Two hundred sixty-two CRS patients were included in this study, thereof, 90 CRS patients (34.4%) with hyponatremia (Na < 135 mmol/L). The diabetes prevalence among CRS patients was high (> 65%) and not related to the serum sodium concentration on admission. In comparison to non-hyponatremic CRS patients, the hyponatremic patients had a lower serum osmolality, hypovolemia was more prevalent (41.1% versus 16.3%, p < 0.001). As possible causes of hypovolemia, diarrhea, a higher number of diuretic drug classes and higher diuretic dosages were found. Hyponatremic and non-hyponatremic CRS patients had a comparable need for renal-replacement therapy (36.7% versus 31.4%) during the hospital stay. However, after discharge, relatively more hyponatremic CRS patients on renal replacement therapy switched to a non-dialysis therapy regimen (50.0% versus 22.2%). Hyponatremic CRS patients showed a trend for a higher in-hospital mortality (15.6% versus 7.6%, p = 0.054), but no difference in the one-year mortality (43.3% versus 40.1%, p = 0.692)., Conclusions: All CRS patients showed a high prevalence of diabetes mellitus and a high one-year mortality. In comparison to non-hyponatremic CRS patients, hyponatremic ones were more likely to have hypovolemia, and had a higher likelihood for temporary renal replacement therapy.

Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor short- and long-term outcomes. There are no specific therapies to reduce mortality related to either AKI or CRS, apart from supportive care and volume status management. Acute renal replacement therapies (RRTs), including ultrafiltration, intermittent hemodialysis, and continuous RRT are used to manage complications of medically refractory AKI and CRS and may restore normal electrolyte, acid-base, and fluid balance before renal recovery. Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient selection. Despite the growing use of RRT in the cardiac intensive care unit, there are few resources for the cardiovascular specialist that integrate the epidemiology, diagnostic workup, and medical management of AKI and CRS with an overview of indications, multidisciplinary team management, and transition off of RRT., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background: Cardiorenal syndrome (CRS), a serious condition with high morbidity and mortality, is characterized by the coexistence of cardiac abnormality and renal dysfunction. There is limited information about CRS in association thalassemia. This study aimed to investigate the prevalence of CRS in thalassemia patients and also associated risk factors., Methods: Thalassemia patients who attended the out-patient clinic of a tertiary care university hospital from October 2016 to September 2017 were enrolled onto this cross-sectional study. Clinical and laboratory findings from 2 consecutive visits, 3 months apart, were assessed. The criteria for diagnosis of CRS was based on a system proposed by Ronco and McCullough. Cardiac abnormalities are assessed by clinical presentation, establishment of acute or chronic heart failure using definitions from 2016 ESC guidelines or from structural abnormalities shown in an echocardiogram. Renal dysfunction was defined as chronic kidney disease according to the 2012 KDIGO guidelines., Results: Out of 90 thalassemia patients, 25 (27.8%) had CRS. The multivariable analysis showed a significant association between CRS and extramedullary hematopoiesis (EMH) (odds ratio (OR) 20.55, p = 0.016); thalassemia type [β 0 /β E vs β 0 /β 0 thalassemia (OR 0.005, p = 0.002)]; pulmonary hypertension (OR 178.1, p = 0.001); elevated serum NT-proBNP (OR 1.028, p = 0.022), and elevated 24-h urine magnesium (OR 1.913, p = 0.016). There was no association found between CRS and frequency of blood transfusion, serum ferritin, liver iron concentration, cardiac T2*, type of iron chelating agents, or urine neutrophil gelatinase-associated lipocalin level., Conclusions: CRS is relatively common in thalassemia patients. Its occurrence is associated with laboratory parameters which are easily measured in clinical practice.

Communication between the heart and kidney occurs through various bidirectional pathways. The heart maintains continuous blood flow through the kidney while the kidney regulates blood volume thereby allowing the heart to pump effectively. Cardiorenal syndrome (CRS) is a pathologic condition in which acute or chronic dysfunction of the heart or kidney induces acute or chronic dysfunction of the other organ. CRS type 3 (CRS-3) is defined as acute kidney injury (AKI)-mediated cardiac dysfunction. AKI is common among critically ill patients and correlates with increased mortality and morbidity. Acute cardiac dysfunction has been observed in over 50% of patients with severe AKI and results in poorer clinical outcomes than heart or renal dysfunction alone. In this review, we describe the pathophysiological mechanisms responsible for AKI-induced cardiac dysfunction. Additionally, we discuss current approaches in the management of patients with CRS-3 and the development of targeted therapeutics. Finally, we summarize current challenges in diagnosing mild cardiac dysfunction following AKI and in understanding CRS-3 etiology.

Low serum sodium concentration has long been recognized as an established marker of short- and long-term morbidity and mortality in patients with heart failure (HF), and is commonly included in various risk prediction models. Mechanisms leading to hyponatremia (e.g. maladaptive neurohormonal activation) could also lead to concurrent decline in serum chloride levels. Besides, chloride has distinct biological roles (e.g. modulation of renal tubular sodium transporters) that are relevant to the pathophysiology and therapy of HF, making it a potent cardiorenal connector. Several clinical studies have recently reported on a potentially overlooked link between low serum chloride levels and adverse outcomes in patients with a wide variety of HF syndromes, which could indeed be stronger than that of sodium. While evidence on predictive value of chloride is accumulating in various patient populations and settings, the limited available interventional studies have so far yielded conflicting results. It remains to be elucidated whether hypochloremia represents a marker of disease severity and prognosis, or it is an actual pathogenetic mechanism, hence being a potential novel target of therapy. Current ongoing studies are designed to better understand the mechanistic aspects of the role of hypochloremia in HF and shed light on its clinical applicability., Competing Interests: No specific financial support was obtained for preparation of this article. The authors declare no conflicts of interest statement., (© 2020 Kazory and Costanzo Published by IMR press.)