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A recent American Heart Association Scientific Statement and Presidential Advisory recognized a new syndrome, the cardiovascular-kidney-metabolic syndrome. This expands our understanding of what has been called cardiorenal syndrome by incorporating the pathophysiological interrelatedness of metabolic risk factors into the previous concept of cardiorenal syndrome. Importantly, perturbation of cardiac or renal physiology combines to produce significant detrimental outcomes. The cardiorenal syndrome is a significant part of the cardiovascular-kidney-metabolic syndrome and contributes to health care cost, disability, and mortality. It is a vexing malady that has generated considerable interest. To understand the syndrome evaluation of its teleological origins is important. In life's beginning, eukaryotes acquired exocytosis for excretion, formed tubular secretory systems for clearance, and a mesenchymal nucleic acid vasoform for nutritional distribution. Those structures progressed to cardiovascular and renal systems of evolving organisms, whose migration to rivers and land imposed complex, coordinated, homeostatic roles to maintain intravascular stability. Tissue mineralization of vertebrate endoskeleton added renal calcium balance regulation, which in kidney failure results in cardiovascular calcification. Insight into cardiorenal disease can be traced to ancient Egyptian and Chinese medicine, through the Scientific Revolution, and into current insights regarding human physiology and pathophysiology. The post-World War II epidemic of cardiovascular mortality generated considerable information on cardiovascular disease, which being higher in patients with kidney disease, drew increasing health concerns. The cardiorenal syndrome was formally introduced in this setting with a focus on ultrafiltration to manage volume overload. An evolutionary review of insight into cardiorenal syndrome will help us better understand the new cardiovascular-kidney-metabolic syndrome. [ABSTRACT FROM AUTHOR]

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cardiorenal syndrome is a condition where is a bidirectional and mutually detrimental relationship between the heart and kidneys. The mechanisms underlying cardiorenal syndrome are multifactorial and complex. Patients with kidney disease exhibit increased cardiovascular risk, presenting as coronary and peripheral artery disease, structural heart disease, arrhythmias, heart failure, and sudden cardiac death, largely occurring because of a systemic proinflammatory state, causing myocardial and vascular remodeling, manifesting as atherosclerotic lesions, vascular and valvular calcification, and myocardial fibrosis, particularly among those with advanced disease. This review summarizes the current understanding and clinical implications of kidney disease in patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

In many countries, the aging population and the higher incidence of comorbid conditions have resulted in an ever-growing need for cardiac interventions. Acute kidney injury (AKI) is a common complication of these interventions, associated with higher mortalities, chronic or end-stage kidney disease, readmission rates, and hospital and post-discharge costs. The AKI pathophysiology includes contrast-associated AKI, hemodynamic changes, cardiorenal syndrome, and atheroembolism. Preventive measures include limiting contrast media dose, optimizing hemodynamic conditions, and limiting exposure to other nephrotoxins. This review article outlines the current state-of-art knowledge regarding AKI pathophysiology, risk factors, preventive measures, and management strategies in the peri-interventional period. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a frequently occurring complication of cardiovascular interventions, and associated with adverse outcomes. Therefore, a clear definition of AKI is of paramount importance to enable timely recognition and treatment. Historically, changes in the serum creatinine and urine output have been used to define AKI, and the criteria have evolved over time with better understanding of the impact of AKI on the outcomes. However, the reliance on serum creatinine for these AKI definitions carries numerous limitations including delayed rise, inability to differentiate between hemodynamics versus structural injury and assay variability to name a few. [ABSTRACT FROM AUTHOR]

Background: Morbid obesity (BMI > 35 kg/m2 with comorbid conditions) is present in 25 - 35% of acute decompensated heart failure (AHF) patients. Prevalence of HF increases with duration of morbid obesity from 30% at 15 years to over 90% at 30 years. There is a need to develop pragmatic therapies that address the unique physical and mental challenges faced by obese AHF patients. Siddha is 5,000 year old Tamil Medicine using yoga and mind-body methods towards higher consciousness. Hunger gratitude Experience (HUGE) is intuitive Siddha fasting method which may improve in-hospital AHF outcomes independent of weight reduction.Case Summary: We present 5 cases of morbidly obese patients with cardiorenal syndrome (CRS) that began intermittent fasting either during their AHF hospitalization or in the outpatient setting for refractory symptoms despite hospitalization. Initiation of fasting correlated with reduction of respiratory distress and edema as well as improvements in psychological wellbeing and functional capacity.Discussion: Siddha fasting mediates hemodynamic and anti-inflammatory effects through natural ketosis and psychological benefits through empowerment in AHF. Potential role of fasting in reducing myocardial workload, coronary steal, angina, volume overload, and CRS needs further study in cardiac patients. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome is the term that describes the interaction between the heart and kidney that leads to diuretic resistance and worsening renal function. Prolonged anuria generally represents irreversible renal failure, and recovery of renal function after prolonged anuria in patients with heart failure has rarely been reported. Moreover, increased central venous pressure including heart failure is associated with impaired renal function. We herein report a rare case of a 46-year-old man with dilated cardiomyopathy who presented with dyspnea and generalized edema. His body weight increased from 90 kg to 128 kg in one year and he was hospitalized. Central venous pressure (CVP) on admission was 33 mmHg. Intravenous catecholamines were not effective; thus, he was started on continuous hemodiafiltration. Anuria occurred after hemodiafiltration due to heart failure, sepsis, and antibiotics use. However, he experienced weight reduction of over 70 kg, under hemodialysis guided by central venous pressure measurement, and renal function recovery after 87 days of anuria. His CVP had improved to 5 mmHg at discharge. This case showed continuous trial to reduce the CVP and raise cardiac output could result in the recovery of impaired renal function even in the presence of prolonged anuria. < Learning objective: We report a rare case of a patient with dilated cardiomyopathy who experienced weight reduction of over 70 kg under hemodialysis guided by central venous pressure (CVP) measurement and renal function recovery after 87 days of anuria due to chronic heart failure. Even in the presence of prolonged anuria, continuous trial to reduce the CVP and raise cardiac output could result in the recovery of impaired renal function.> [ABSTRACT FROM AUTHOR]

To describe the incidence, associated characteristics, and outcomes of the maximum severity of acute kidney injury (AKI) in a heterogeneous population of critically ill children with cardiac disease. Retrospective cohort study. Pediatric cardiac intensive care unit (PCICU). Patients admitted to the PCICU. None. From January 2018 to July 2020 all patients admitted to a tertiary PCICU were included. Only the first admission was considered. Neonates ≤seven days old were excluded. Of 742 patients, 53 were medical cases, 69 catheterization laboratory cases, and 620 surgical cases (with five subgroups). The median age was 2.47 years (interquartile range [IQR], 0.38-9.85 years), with a median Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score of 2 (IQR, 1-3). Median PCICU length of stay was three days (IQR, 2-7 days), and 21 (2.8%) patients died. Any incidence of AKI occurred in 70% of patients, 26% of which were classified as mild (stage 1) and 43% as severe (stages 2 and 3). AKI was diagnosed by urine output criteria in 56%, serum creatinine in 28%, and both in 16% of patients. Severe AKI occurred in subgroups as follows: medical (38%), catheterization laboratory (45%), correction (35%), palliation (55%), transplantation (85%), mechanical assistance (70%), and redo surgery (58%). Severe AKI patients were significantly older (p = 0.004), had a higher Pediatric Index of Mortality 3 score (p = 0.0004), had a higher cumulative fluid balance (p < 0.0001), and had a longer cardiopulmonary bypass time (p < 0.0001). Early AKI (≤24 hours from admission) was the most frequent presentation, with a greater proportion of severe cases in the early group compared with the intermediate (>24 and ≤48 hours) and late (>48 hours) (p < 0.0001) groups. Presentation of late severe AKI had a higher mortality (odds ratio, 4.9; 95% confidence interval, 1.8-15; p = 0.001). Severe AKI occurs in 43% of cardiac children and is diagnosed early, most often by urine output criteria. Severe AKI incidence varies significantly within subgroups of cardiac patients. Late AKI is associated with worse outcomes. [ABSTRACT FROM AUTHOR]

L'hyperkaliémie récidivante peut conduire à une sous-utilisation des inhibiteurs du système rénine-angiotensine-aldostérone. Nous présentons une analyse des données françaises de l'étude PROKALE, qui a évalué la prise en charge de l'hyperkaliémie dans cinq pays européens. Un examen rétrospectif des dossiers de patients adultes non dialysés ayant présenté au moins deux épisodes d'hyperkaliémie ≥ 5,5 mEq/L sur une période de 12 mois a été effectué. En France, 115 médecins (57 néphrologues et 58 cardiologues) ont participé à l'étude, et 295 patients ont été étudiés. L'âge moyen était de 68 ans ; 212 patients (71,9 %) avaient une insuffisance rénale chronique, 108 (36,6 %) une insuffisance cardiaque chronique et 102 (34,6 %) un diabète sucré. Le nombre moyen d'épisodes hyperkaliémiques rapportés était de 2,3. Sur 90 hospitalisations, 24 (26,7 %) étaient directement liées à un épisode d'hyperkaliémie. Les traitements utilisés dans la prise en charge de l'hyperkaliémie lors du premier épisode étaient les diurétiques de l'anse (144 patients [48,8 %]), les résines échangeuses de cations (135 [45,8 %]), un régime pauvre en potassium (31 [10,5 %]) ou le bicarbonate de sodium (31 [10,5 %]). Entre les deux épisodes d'hyperkaliémie consécutifs documentés, la proportion des patients traités par des inhibiteurs du système rénine-angiotensine-aldostérone a diminué de 42,4 % à 34,6 %. Des interruptions du traitement par les inhibiteurs du système rénine-angiotensine-aldostérone sont observées en contexte d'hyperkaliémie récidivante. L'hyperkaliémie récidivante représente une cause majeure d'hospitalisation. Des stratégies de prise en charge plus efficaces sont nécessaires. Recurrent hyperkalaemia may result in underutilisation of renin-angiotensin-aldosterone system inhibitors. We report an analysis of French data from the PROKALE retrospective study, which assessed the management of recurrent hyperkalaemia in five European countries. A retrospective chart review including patients not on dialysis with two or more hyperkalaemia episodes ≥ 5.5 mEq/L documented within a 12-month observation period was performed. In France, 115 physicians (57 nephrologists et 58 cardiologists) participated in the study and 295 patients were studied in this analysis. Mean age was 68 years; 212 patients (71.9%) had chronic kidney disease, 108 (36.6%) had chronic heart failure and 102 (34.6%) had diabetes mellitus. The mean number of documented hyperkalaemic episodes was 2.3. A total of 90 hospitalizations occurred during the observation period, of which 24 (26.7%) were directly related to a hyperkalaemic episode. At the time of the first documented hyperkalaemic episode, measures used for the management of hyperkalaemia included loop diuretics (144 patients [48.8%]), sodium/calcium polystyrene sulphonate (135 patients [45.8%]), a low-potassium diet (31 patients [10.5%]) and sodium bicarbonate (31 patients [10.5%]). Between the two consecutive hyperkalaemic episodes documented, the proportion of patients on renin-angiotensin-aldosterone system inhibitors treatment decreased from 42.4% to 34.6%. Renin-angiotensin-aldosterone system inhibitors treatment interruptions were observed in the setting of recurrent hyperkalaemic episodes. Recurrent hyperkalaemia is a major cause of hospitalizations. More effective strategies for the prevention of recurrent hyperkalaemia are needed. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) comprises approximately one-half of all diagnoses of heart failure. There is significant overlap of this clinical syndrome with chronic kidney disease (CKD), with many shared comorbid conditions. The presence of CKD in patients with HFpEF is one of the most powerful risk factors for adverse clinical outcomes, including death and heart failure hospitalization. The pathophysiology linking HFpEF and CKD remains unclear, but it is postulated to consist of numerous bidirectional pathways, including endothelial dysfunction, inflammation, obesity, insulin resistance, and impaired sodium handling. The diagnosis of HFpEF requires certain criteria to be satisfied, including signs and symptoms consistent with volume overload caused by structural or functional cardiac abnormalities and evidence of increased cardiac filling pressures. There are numerous overlapping metabolic clinical syndromes in patients with HFpEF and CKD that can serve as targets for intervention. With an increasing number of therapies available for HFpEF and CKD as well as for obesity and diabetes, improved recognition and diagnosis are paramount for appropriate management and improved clinical outcomes in patients with both HFpEF and CKD. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The adverse prognostic implications of significant renal dysfunction during treatment of acute decompensated heart failure (HF) in patients with obese HF and preserved ejection fraction (HFpEF) provide strong rationale for development of therapeutic strategies that enhance decongestion while preserving renal function in this cohort. The combination of preload sensitivity, intrinsic renal dysfunction related to obesity, glomerular hyperfiltration, reversible renal hypoperfusion (poor renal arterial perfusion and renal venous congestion), and decreased systemic vascular resistance in obesity may predispose patients to renal hemodynamic compromise during diuresis. Thus, serum creatinine increase should not be evaluated in isolation but rather considered in the context of the entire clinical picture in patients with obese HFpEF. [ABSTRACT FROM AUTHOR]

• GXD largely improved cardiac function in rats with CRS2. • GXD partially prevented renal dysfunction in rats with CRS2. • Network pharmacology disclosed that the PI3K/AKT/NF-κB signaling pathway may be involved in the treatment of CRS2. • PI3K/AKT/ NF-κB signaling pathway in rats with CRS2 was prevented by GXD. • These data provide evidence that GXD is a promising therapeutic intervention for the management of CRS2. Cardiorenal syndromes type II (CRS2) is a multi-organ ailment that manifests as a combination of cardiac and renal dysfunction, resulting in chronic kidney disease due to chronic cardiac insufficiency. It affects at least 26 million people worldwide, and its prevalence is increasing. Gualou Xiebai Decoction (GXD), a traditional Chinese medicine (TCM) with a rich history of application in the management of coronary artery disease, has been explored for its potential therapeutic benefits in CRS2. Nevertheless, the mechanism by which GXD alleviates CRS2 remains obscure, necessitating further investigation. The aim of this study was to assess the effects of the ethanolic extract of GXD on CRS2 and to elucidate the underlying mechanism in a rat model of myocardial infarction, offering a potential target for clinical treatment for CRS2. A rat model of CRS2 was induced by surgical myocardial infarction and treated with GXD for 10 weeks. Cardiac function was assessed using echocardiography, while serum and urine biochemistry were analyzed to evaluate potential cardiac and renal damage. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active compounds, potential therapeutic targets, and interventional pathways through which GXD could potentially exert its effects on CRS2. Subsequently, these predictions were confirmed in vivo and vitro through various analyses. The current investigation employed echocardiography to exhibit the apparent cardiac remodeling following the induction of myocardial infarction. Damage to the heart and kidneys of CRS2 rats was effectively ameliorated by administration of GXD. The outcomes derived from the analyses of HE and Masson staining indicated that the pathological damage to the heart and kidney tissues of rats in the GXD groups was considerably alleviated. Using network pharmacology analysis, AKT1, IL-6, and TNF-α were identified as plausible therapeutic targets for the treatment of CRS with GXD. Subsequent functional and pathway enrichment analysis of the underlying targets disclosed that the PI3K/AKT/NF-κB signaling pathway may be involved in the mechanism of GXD in the treatment of CRS2. Immunohistochemical, western blot, RT-PCR and immunofluorescence staining were employed to demonstrate that GXD can regulate the PI3K/AKT/NF-κB signaling pathway in the CRS2 rat model. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the effect of diosmetin, which was one of the potential active components of GXD analysed by compound-target-disease network, on p-PI3K and p-AKT in vitro. The findings of this study suggest that GXD improves cardiac and renal function in CRS2 rats and that the underlying mechanism involves inhibition of the PI3K/AKT/NF-κB pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Congestive heart failure (CHF) entails a complex interaction between the heart and the kidney that represents a clinical entity called cardiorenal syndrome (CRS). One of the mechanisms underlying CRS includes increased intra-abdominal pressure (IAP). We examined the effect of elevated IAP on kidney function in rats with low- and high-output CHF.Methods and Results: Rats with compensated and decompensated CHF induced by means of aortocaval fistula, rats with myocardial infraction (MI) induced by means of left anterior descending artery ligation, and sham control rats were subjected to either 10 or 14 mm Hg IAP. Urine flow (V), Na+ excretion (UNaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. The effects of pretreatment with tadalafil (10 mg/kg orally for 4 days) on the adverse renal effects of IAP were examined in decompensated CHF and MI. Basal V and GFR were significantly lower in rats with decompensated CHF compared with sham control rats. Decompensated CHF rats and MI rats subjected to 10 and 14 mm Hg IAP exhibited more significant declines in V, UNaV, GFR and RPF than compensated and sham controls. Elevated IAP also induced tubular injury, as evidenced by significantly increased absolute urinary excretion of neutrophil gelatinase-associated lipocalin. In addition, in a nonquantitative histologic analysis, elevated IAP was associated with increase in necrosis and cell shedding to the tubule lumens, especially in the decompensated CHF subgroup. Pretreatment of decompensated CHF rats and MI rats with tadalafil ameliorated the adverse renal effects of high IAP.Conclusions: Elevated IAP contributes to kidney dysfunction in high- and low-cardiac output CHF. IAP induces both hemodynamic alterations and renal tubular dysfunction. These deleterious effects are potentially reversible and can be ameliorated with the use of phosphodiesterase-5 inhibition. [ABSTRACT FROM AUTHOR]

Objective An association between central venous pressure and acute kidney injury (AKI) has been observed following cardiac surgery, but it is unknown whether this reflects intravascular volume status or impaired right ventricular (RV) myocardial performance. This study was performed to test the hypothesis that decreased RV peak longitudinal strain (PLSS), as measured by 2-dimensional speckle-tracking echocardiography, is associated with AKI following cardiac surgery. Design Retrospective observational cohort study. Setting Cardiovascular intensive care unit in a 576-bed referral hospital. Participants Adult patients having undergone cardiac surgery in whom a transthoracic echocardiogram (TTE) was performed within 48 hours after chest closure. Interventions This was a retrospective study. Urine output and serum creatinine values were recorded at baseline and for 48 hours after surgery. Statistical analysis was performed to identify differences in baseline demographic and echo-derived values between patients with and without postoperative AKI criteria. Measurements and Main Results One hundred ninety-nine subjects had postprocessing of TTE performed. AKI was observed in 87% of patients (173 of 199). Age, body mass index, and preoperative serum creatinine were higher in the AKI group. The mean PLSS was -17.2% ± 4.3% versus -17.1% ± 3.7% in patients with AKI versus those without (p = 0.95). The calculated RV systolic pressure was elevated in the AKI group compared to the non-AKI group (38.9 ± 9.9 v 34.6 ± 7.9 mmHg, p = 0.02). Conclusion In this cohort of cardiac surgery patients, speckle-tracking analysis of RV myocardial performance was feasible. Elevated RV systolic pressure associated with AKI, while speckle tracking-derived echocardiography measurements did not. [ABSTRACT FROM AUTHOR]

Purpose of review: Right-sided heart failure, which is often present in the setting of advanced heart failure, is associated with cardiac cachexia, the cardiorenal syndrome, and adverse outcomes. Improved understanding of venous congestion of the splanchnic circulation, which may play a key role in the pathogenesis of right-sided heart failure, could lead to novel therapeutics to ameliorate heart failure. Here we provide an overview of right-sided heart failure, splanchnic hemodynamics, fluid homeostasis, and the intestinal microenvironment. We review recent literature to describe pathophysiologic mechanisms and possible therapeutics. Recent findings: Several possible mechanisms centered around upregulation of sodium–hydrogen exchanger-3 (NHE3) may form a causal link between right ventricular dysfunction, splanchnic congestion, and worsening heart failure. These include an anaerobic environment in enterocytes, resulting in reduced intracellular pH; increased sodium absorption by the gut via NHE3; decreased pH at the intestinal brush border thus altering the gut microbiome profile; increased bacterial synthesis of trimethylamine N-oxide; and decreased bacterial synthesis of short-chain fatty acids causing abnormal intestinal barrier function. Summary: Splanchnic congestion in the setting of right-sided heart failure may serve an important role in the pathogenesis of advanced heart failure, and further exploration of these mechanisms may lead to new therapeutic advances. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV), a non-invasive measurement of the sympathetic-vagal balance, has been demonstrated as a predictor of long-term survival in various patient populations. However, its predictive value in patients with end-stage renal disease (ESRD) has not been evaluated in a long-term follow-up study.Methods: Prospective data collected for 41 patients with chronic hemodialysis (age 59 ± 10 years, men 51.3%, diabetes mellitus 31%, and duration of dialysis 64 ± 50 months) who underwent a 5-minute electrocardiogram (ECG) recording as a baseline for frequency domain HRV analysis.Results: During a median follow-up of 150.2 months from 2003 to 2014, 15 (35.7%) patients died (3 due to cardiac causes and 12 due to non-cardiac causes). The Cox proportional hazards model suggested that the low frequency versus high frequency signal (LF/HF) of a high ratio for the HRV and diabetes mellitus were two independent predictors of mortality (hazard ratios 3.028 and 3.494; p = 0.033 and 0.022, respectively). Less reduction in MAP during dialysis showed borderline significance of long-term survival than those with larger drop (p = 0.058).Conclusion: A short ECG recording and an analysis of the frequency domain of the HRV is clinically predictive of the long-term survival of patients with chronic hemodialysis. [ABSTRACT FROM AUTHOR]

Objective Venous congestion is a possible mechanism leading to acute kidney injury (AKI) following cardiac surgery. Portal vein flow pulsatility is an echographic marker of cardiogenic portal hypertension and might identify clinically significant organ congestion. This exploratory study aims to assess if the presence of portal flow pulsatility measured by transthoracic echography in the postsurgical intensive care unit is associated with AKI after cardiac surgery. Design Retrospective cohort study. Setting Specialized care university hospital. Participants Patients who underwent cardiac surgery between May 2015 and February 2016 and had at least 1 Doppler assessment of portal flow performed by the attending critical care physician during the week following cardiac surgery. Interventions The association between portal flow pulsatility defined as a pulsatility fraction ≥50% and the risk of subsequent AKI was assessed using univariate and multivariate logistic regression analysis. Measurements and Main Results The files of 132 consecutive patients were reviewed and 102 patients were included in the analysis. Significant portal flow pulsatility was detected in 38 patients (37.3%) in the week following surgery. During this period, 60.8% developed AKI and 13.7% progressed to severe AKI. The detection of portal flow pulsatility was associated with an increased risk for the development of AKI (odds ration [OR] 4.31, confidence interval [CI] 1.50-12.35, p = 0.007). After adjustment, portal flow pulsatility and AKI were independently associated (OR 4.88, CI 1.54-15.47, p = 0.007). Conclusions Assessment of portal flow using Doppler ultrasound at the bedside might be a promising tool to detect patients at risk for AKI due to cardiogenic venous congestion. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Type 1 cardiorenal syndrome (CRS) is an acute renal failure in patients with acute decompensated heart failure with an incidence of 24% to 45%. The aim of our study was to investigate the significance of new renal biomarkers to predict type 1 CRS. PATIENTS AND METHODS: The study included 111 patients with acute decompensated heart failure diagnosed at the Istanbul Medical Faculty Emergency Department between 2014 and 2016, and 24 healthy volunteers. All urine samples were stored at -80°C after centrifugation. Samples were run according to the instructions of TIMP-2, ILGF-7, KIM-1, and IGFBP-7 ELISA kits. Diuretic treatments were then administered with intravenous administration of at least 80 mg furosemide per day. Follow-up biochemical and spot urine specimens were taken after 72 hours. For statistical analysis, SPSS version 21.0 statistical software was used. Significance was evaluated at p<0.05. RESULTS: The baseline creatinine level was measured as 1.33 ± 0.39 mg/dL in the heart failure group. It was seen that 67% (75) of the patients had increased creatinine levels and developed type 1 CRS. ILGF-7, TIMP-2, and (ILGF-7 * TIMP-2) values were significantly higher in patients with cardiorenal syndrome when we separated the two groups as patients with and without cardiorenal syndrome (0.40 (0.25-0.71), p1: 0.049/2.40 (1.42-3.70), p2: 0.003/1.15 (0.29-2.43), p3: 0.001). CONCLUSIONS: Renal tubular markers reveal promising developments in the pathophysiology of cardiorenal syndrome in light of recently obtained data. Renal tubular biomarkers may have the potential to be a predictor of heart failure and cardiorenal syndrome. [ABSTRACT FROM AUTHOR]

Worsening renal function and azotemia in patients with heart failure (HF) are strongly associated with disease severity and poor prognosis. Increasing interest in this correlation led to the description and classification of cardiorenal syndrome (CRS). We evaluated the role of neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of CRS in dogs with HF. Ten healthy dogs and 31 dogs admitted with HF were included in our study. NGAL and troponin-I were measured on samples collected on the day of admission; creatinine was measured on admission and again on day 7. The CRS group was defined as subsequently developing renal azotemia. Of 31 dogs with HF, 20 were included in the HF group, and 11 were included in the CRS group. The admission NGAL concentrations of the CRS group were significantly higher than those of other groups (p < 0.001). The severity of HF evaluation based on the modified New York Heart Association classification showed significant correlation with NGAL (p < 0.001) and troponin-I (p = 0.009) concentration. However, only serum NGAL concentration at admission was significantly associated with the development of CRS in dogs with HF (p = 0.021). The admission serum NGAL = 16.0 ng/mL (optimal cutoff value) had a sensitivity of 90.9% and specificity of 90.0% in predicting the development of CRS. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a risk factor for cardiac and renal complications; its effect on cardiorenal syndromes is unknown. 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. 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. 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cardio-Renal Syndrome (CRS) is a condition, which is more frequently observed in clinical practice. The aim of this study is to explore nutritional status and intrarenal arterial stiffness in patients affected by CRS. PATIENTS AND METHODS: 14 consecutive CRS patients, screened for anthropometry, biochemistry, nutritional and metabolic status underwent renal Doppler ultrasound and wholebody bioimpedance spectroscopy (BIS). RESULTS: We found a positive correlation between phase angle (PA) and CKD-EPI and MDRD (p=0.011 and p=0.007), and between body mass index and renal resistive index (RRI) (p=0.002). Finally, we found a negative correlation between fat-free mass and RRI (p=0.024). CONCLUSIONS: Body composition assessment may improve the care of patients with chronic kidney disease (CKD). Also, BIS may help identify changes in hydration status in CKD patients resulting as a significant predictor of mortality. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) is increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, Recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into five distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from FH and CKD clinical trials. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Croatica is the property of Croatian Academy of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Croatica is the property of Croatian Academy of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background-Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature. Methods and Results-Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46; P<0.001) with no incremental contribution from serum sodium (P=0.49). Hypochloremic versus nonhypochloremic patients exhibited renal wasting of chloride (P=0.04) and of chloride relative to sodium (P=0.01), despite better renal free water excretion (urine osmolality 343±101 mOsm/kg versus 475±136; P<0.001). Hypochloremia was associated with poor diuretic response (odds ratio, 7.3; 95% confidence interval, 3.3-16.1; P<0.001). In the interventional pilot, lysine chloride supplementation was associated with an increase in serum chloride levels of 2.2±2.3 mmol/L, and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in amino terminal, pro B-type natriuretic peptide, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio. Conclusions-Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background--The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro) vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Methods and Results--Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria. Conclusions--The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a -galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and realtime PCR were used to evaluate the expressions of galectin-3 in heart and renal. RESULTS: Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced signi f icant ly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. CONCLUSIONS: Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway. [ABSTRACT FROM AUTHOR]

Background: Worsening renal function in heart failure may be related to increased venous congestion, decreased cardiac output, or both. Diuretics are universally used in acute decompensated heart failure, but they may be ineffective and may lead to azotemia. We aimed to compare the decongestive properties of a urine output-guided diuretic adjustment and standard therapy for the management of cardiorenal syndrome in acute decompensated heart failure.Methods and Results: Data were pooled from subjects randomized to the stepwise pharmacologic care algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials. Patients treated with SPCA (n = 94) were compared with patients treated with standard decongestive therapy (SDT) that included intravenous loop diuretic use (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed for net fluid balance, weight loss, and changing renal function. The SPCA group had higher degrees of jugular venous pressure (P < .0001) at the time of cardiorenal syndrome. The group that received SPCA had more weight change (-3.4 ± 5.2 lb) and more net fluid loss (1.705 ± 1.417 L) after 24 hours than the SDT group (-0.8 ± 3.4 lb and 0.892 ± 1.395 L, respectively; P < .001 for both) with a slight improvement in renal function (creatinine change -0.1 ± 0.3 vs 0.0 ± 0.3 mg/dL, respectively; P = .03).Conclusions: Compared with SDT, patients who received an intensification of medication therapy for treating persisting congestion had greater net fluid and weight loss without being associated with renal compromise. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ultrasound is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Studia Universitatis Vasile Goldis, Physical Education & Physical Therapy Series is the property of Vasile Goldis University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To examine the impact of postoperative acute kidney injury (AKI) on the long-term risk of myocardial infarction, heart failure, stroke, and all-cause mortality after elective cardiac surgery. The authors investigated whether time of onset of AKI altered the association between AKI and the adverse events. Design Population-based cohort study in 2006-2011. Setting Two university hospitals. Participants Adult elective cardiac surgical patients. Interventions None. Measurements and Main Results AKI was defined as an increase in baseline creatinine according to the Kidney Disease Improving Global Outcomes criteria. AKI was defined within 30 days of surgery, and also analyzed as early- or late-onset AKI. The authors followed patients from postoperative day 30 until hospitalization with myocardial infarction, heart failure, stroke, or death. Adjustment for confounding factors was done using propensity scores and standardized-mortality-ratio weights. A total of 1,457 (30.7%) of 4,742 patients developed AKI within 30 days of surgery and 470 (9.9%) patients experienced a composite cardiovascular endpoint. Comparing patients with and without postoperative AKI, weighted hazard ratio (HR) and 95% confidence intervals (CI) of 5-year risk of the composite cardiovascular endpoint was 1.41 (95% CI: 1.11-1.80). For each endpoint separately the weighted HR was similarly increased. Ninety-one days to 5-year weighted HR of all-cause mortality was 1.37 (95% CI: 1.05-1.80). The effect of AKI was similar for early- and late-onset AKI. Conclusions Early- and late-onset AKI within 30 days of elective cardiac surgery was associated with a similarly increased 5-year risk of myocardial infarction, heart failure, stroke, and increased all-cause mortality. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

OBJECTIVE: To study the protective effects of valsartan (Val) and benazepril, (Ben) combined with atorvastatin (Ato), on cardiorenal syndrome (CRS) in rats. MATERIALS AND METHODS: After establishing cardiorenal syndrome model, the rats were randomly divided into control, Ato, Ben+Ato and Val+Ato groups, which were treated with corresponding drugs. Before and 4 weeks after treatment, the serum creatinine (Scr), blood urea nitrogen (BUN), type-B natriuretic peptide (BNP), aldosterone (ALD), angiotensin (Ang) II, C-reactive protein (CRP), blood lipid and urine protein were determined. The left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) as well as maximum rising and falling rates of left ventricular pressure (±dp/dt-max) were detected. The heart weight index was also determined. RESULTS: 6, 3, 1 and 2 rats control, Ato, Ben+Ato and Val+Ato groups died, respectively. Compared with control group, the serum Cr, BUN, BNP, ALD, CRP and urinary protein levels in treatment groups significantly decreased, and the blood lipid level, LVDP, LVEDP and heart weight index significantly decreased, with increased LVSP. No statistically significant difference was observed among treatment groups. CONCLUSIONS: Valsartan and benazepril, combined with atorvastatin, can have significant protective effects on cardiorenal functions of rats with CRS, with no significant difference between these two drugs. [ABSTRACT FROM AUTHOR]

Background Differentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF. Methods and Results A total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (>1296 pg/mL) and BUN/creat (>17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6–1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2–2.7, P = .008, P interaction = .005). Conclusions In the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis. [ABSTRACT FROM AUTHOR]

Simultaneous dysfunction of the heart and the kidney represents a distinct spectrum of disease states composed of complex clinical scenarios with adverse outcomes. Worsening renal function (WRF) in the setting of acute decompensated heart failure (ADHF) is one such clinical setup for which the underlying mechanisms are poorly understood. Apparent discrepancies exist between the emerging data on the cardiorenal interactions of patients with ADHF and contemporary concepts such as the low forward flow or the high backward pressure hypotheses. The findings of recent retrospective studies also suggest that apparent “improvement in renal function” might be yet another risk factor for untoward outcomes in this patient population, further challenging our current understanding of the cardiorenal interactions. Besides, these data do not seem to fully support our conventional thinking about other aspects of these interactions such as the independent adverse impact of WRF on the outcomes of patients with ADHF, pointing to congestion as a possibly overlooked factor. In this article, we provide an overview of these emerging controversial issues with the goal of identifying the areas where clinical research could be most helpful, because it is of paramount importance to characterize the pathways leading to WRF in ADHF to develop a mechanistically relevant management strategy. Although the paucity of data coupled with the complexity of this field precludes any firm conclusion, these discussions are meant to prompt clinicians and researchers to revisit a number of long-believed concepts surrounding the cardiorenal interactions in ADHF. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients such as patients with postcardiotomy cardiogenic shock or life-threatening respiratory failure. Acute kidney injury (AKI) that develops during ECMO is associated with a very poor outcome, possibly because of accumulated extravascular water causing interstitial overload, impaired oxygen transport through tissues, and increased extravascular lung water volume with impaired O 2 transport. Increased water is associated with subsequent organ dysfunction, particularly of the heart, lungs, and brain. Based on single-center studies, the incidence of AKI is 70–85% in ECMO patients. Therefore, renal replacement therapy is required in approximately 50% of these patients. This review summarizes three modalities that can be used to introduce renal replacement therapy to patients on ECMO, the pathophysiology of AKI in ECMO, and the impact of AKI on mortality. This review also identifies specific research-focused questions that need to be addressed to predict AKI early and to improve outcomes in this at-risk adult population. [ABSTRACT FROM AUTHOR]

Despite major advances in pharmacological therapy and cardiac devices, heart failure patients continue to be frequently (re-)hospitalized with signs and symptoms of fluid overload. Diuretics improve the symptoms of fluid overload, but their effectiveness is reduced by a number of factors including excess salt intake, underlying chronic kidney disease, renal adaptation to their actions and neurohormonal activation. Ultrafiltration (UF) is a mechanical method of fluid removal with several potential advantages over diuretic-based conventional therapies: several recent studies have demonstrated favorable clinical response to UF therapy. Such studies have shown that removal of large amounts of isotonic fluid, in addition to relieving symptoms of congestion, can improve exercise capacity, reduce cardiac filling pressures, restore diuretic responsiveness, and portend a favorable effect on cardio-pulmonary, cardiorenal interactions, and neurohormonal hyperactivation. However, despite these proposed benefits, so far, no clinical study has yet been carried out to explore the impact of UF therapy on hard clinical endpoints such as long-term mortality. In this article, we review a number of mechanistic aspects of UF therapy, with particular emphasis on cardio-pulmonary and cardiorenal interactions, and revisit the results of more recent clinical trials in order to highlight the characteristics that can help identify patients who are more likely to benefit from this therapeutic modality. [ABSTRACT FROM AUTHOR]

Prior studies have demonstrated adverse risk associated with baseline and worsening renal function in acute heart failure, but none has modeled the trajectories of change in renal function and their impact on outcomes.We used linear mixed models of serial measurements of blood urea nitrogen and creatinine to describe trajectories of renal function in 1962 patients with acute heart failure and renal dysfunction enrolled in the Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function study. We assessed risk of 180-day mortality and 60-day cardiovascular or renal readmission and used Cox regression to determine association between renal trajectories and outcomes. Compared with patients alive at 180 days, patients who died were older, had lower blood pressure and ejection fraction, and higher creatinine levels at baseline. On average for the entire cohort, creatinine rose from days 1 to 3 and increased further after discharge, with the trajectory dependent on the day of discharge. Blood urea nitrogen, creatinine, and the rate of change in creatinine from baseline were the strongest independent predictors of 180-day mortality and 60-day readmission, whereas the rate of change of blood urea nitrogen from baseline was not predictive of outcomes. Baseline blood urea nitrogen >35 mg/dL and increase in creatinine >0.1 mg/dL per day increased the risk of mortality, whereas stable or decreasing creatinine was associated with reduced risk.Patients with acute heart failure and renal dysfunction demonstrate variable rise and fall in renal indices during and immediately after hospitalization. Risk of morbidity and mortality can be predicted based on baseline renal function and creatinine trajectory during the first 7 days.URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458. [ABSTRACT FROM AUTHOR]

Abstract: Cardiorenal syndrome (CRS) is an umbrella term that defines disorders of the heart and kidneys whereby “acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”. The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. Dysfunction of one organ may lead to dysfunction of the other. CRS was recently sub-classified into 5 types primarily based upon the organ that initiated the insult as well as the acuity and chronicity of disease. Development of CRS is associated with increased morbidity, hospital stay, cost of healthcare and mortality. Newer biomarkers have shown potential for early diagnosis of CRS. [Copyright &y& Elsevier]

Background: Differentiation of HF-induced renal dysfunction (RD) from irreversible intrinsic kidney disease is challenging, likely related to the multifactorial pathophysiology underlying HF-induced RD. In contrast, HF-induced liver dysfunction results in characteristic laboratory abnormalities. Given that similar pathophysiologic factors are thought to underlie both conditions, and that the liver and kidneys share a common circulatory environment, patients with laboratory evidence of HF-induced liver dysfunction may also have a high incidence of potentially reversible HF-induced RD. Methods and Results: Hospitalized patients with a discharge diagnosis of HF were reviewed (n = 823). Improvement in renal function (IRF) was denned as a 20% improvement in estimated glomerular filtration rate (eGFR). An elevated international normalized ratio (INR; odds ratio [OR] 2.8; P < .001), bilirubin (BIL; OR 2.2; P < .001), aspartate aminotransferase (AST; OR 1.8; P = .004), and alanine aminotransferase (ALT; OR 2.1; P = .001) were all significantly associated with IRF. Among patients with baseline RD (eGFR ≤45 mL min-1 1.73 m-2), associations between liver dysfunction and IRF were particularly strong (INR: OR 5.7 [P < .001]; BIL: OR 5.1 [P < .001]; AST: OR 2.9 [P = .005]; ALT: OR 4.8 [P < .001]). Conclusions: Biochemical evidence of mild liver dysfunction is associated with reversible RD in decompensated HF patients. In the absence of methodology to directly identify HF-induced RD, signs of HF-induced dysfunction of other organs may serve as an accessible method by which HF-induced RD is recognized. [ABSTRACT FROM AUTHOR]

Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background: Digitalis glycosides are known to improve the hemodynamic and neurohormonal perturbations that contribute to heart failure (HF)–induced renal dysfunction (RD). The objective of this study was to determine if randomization to digoxin is associated with improvement in renal function (IRF) and to evaluate if patients with digoxin-induced IRF have improved clinical outcomes. Methods and Results: Patients in the Digitalis Investigation Group (DIG) dataset with protocol-driven 1-year serum creatinine levels (performed in a central laboratory; n = 980) were studied. IRF was defined as a postrandomization ≥20% increase in estimated glomerular filtration rate (eGFR). IRF occurred in 15.5% of the population (mean improvement in eGFR 34.5 ± 15.4%) and was more common in patients randomized to digoxin (adjusted odds ratio 1.6; P = .02). In patients without IRF, digoxin was not associated with reduced death or hospitalization (adjusted hazard ratio [HR] 0.96, 95% CI 0.8–1.2; P = .67). However, in the group with IRF, digoxin was associated with substantially improved hospitalization-free survival (adjusted HR 0.49, 95% CI 0.3–0.8; P = .006; P interaction = .026). Conclusions: In this subset of the DIG trial, digoxin was associated with long-term improvement in kidney function and, in patients demonstrating this favorable renal response, reduction in death or hospitalization. Additional research is necessary to confirm these hypothesis-generating findings. [Copyright &y& Elsevier]

Abstract: Background: Protein carbamylation, a posttranslational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. We examine the relationship between plasma protein-bound homocitrulline (PBHCit) levels, a marker of protein lysine residue carbamylation, with cardiorenal function and long-term outcomes in chronic systolic heart failure (HF). Methods and Results: In 115 patients with chronic systolic HF (left ventricular ejection fraction ≤35%), we measured plasma PBHCit by quantitative mass spectrometry and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse long-term events (death, cardiac transplantation) were tracked for 5 years. In our study cohort, the median PBHCit level was 87 (interquartile range 59–128) μmol/mol lysine. Higher plasma PBHcit levels were associated with poorer renal function (estimated glomerular filtration rate [eGFR]: Spearman r = −0.37; P < .001), cystatin C (r = 0.31; P = .001), and elevated plasma amino-terminal pro–B-type natriuretic peptide (NT-proBNP) levels (r = 0.26; P = .006), but not with markers of systemic inflammation or oxidant stress (high-sensitivity C-reactive protein and myeloperoxidase [MPO]: P > .10 for each). Furthermore, elevated plasma PBHCit levels were not related to indices of cardiac structure or function (P > .10 for all examined) except modestly with increased right atrial volume index (r = 0.31; P = .002). PBHCit levels predicted adverse long-term events (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.3–2.6; P < .001), including after adjustment for age, eGFR, MPO, and NT-proBNP (HR 1.9, 95% CI 1.2–3.1; P = .006). Conclusions: In chronic systolic HF, protein carbamylation is associated with poorer renal but not cardiac function, and portends poorer long-term adverse clinical outcomes even when adjusted for cardiorenal indices of adverse prognosis. [Copyright &y& Elsevier]

Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment.Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03).An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. [ABSTRACT FROM AUTHOR]

Urine albumin excretion is an important predictor of adverse cardiovascular events in various populations. Its correlation in patients with acute heart failure has not been described.This prospective, observational study included 115 patients presenting with acute heart failure. The urine albumin/creatinine ratio (UACR) was measured from spot urine samples collected on days 1 and 7 of hospitalization. Median UACR decreased from 83 to 22 mg/gCr on days 1 and 7, respectively (P<0.0001). The proportion of patients with normoalbuminuria (UACR <30 mg/gCr) increased from 31% on day 1 to 60% on day 7, whereas the proportion with microalbuminuria (UACR between 30 and 299 mg/gCr) and macroalbuminuria (UACR ≥300 mg/gCr) decreased, respectively, from 42% and 27% on day 1 to 30% and 10% on day 7 (P<0.0001). These changes in UACR were correlated with changes in serum bilirubin and N-terminal pro b-type natriuretic peptide concentrations (correlation coefficients 1.087 and 0.384, respectively; 95% confidence interval, 0.394-1.781 and 0.087-0.680, respectively; and P=0.003 and 0.013, respectively), although they were not correlated with change in estimated glomerular filtration rate.In this sample of patients presenting with acute heart failure, urine albumin excretion was often increased at admission to the hospital and decreased significantly within 7 days of treatment. The decrease was correlated with serum N-terminal pro b-type natriuretic peptide and bilirubin concentrations, although neither with baseline nor with changes in indices of renal function. [ABSTRACT FROM AUTHOR]

Abstract: Longstanding experimental evidence supports the role of renal venous hypertension in causing kidney dysfunction and “congestive renal failure.” A focus has been heart failure, in which the cardiorenal syndrome may partly be due to high venous pressure, rather than traditional mechanisms involving low cardiac output. Analogous diseases are intra-abdominal hypertension and renal vein thrombosis. Proposed pathophysiologic mechanisms include reduced transglomerular pressure, elevated renal interstitial pressure, myogenic and neural reflexes, baroreceptor stimulation, activation of sympathetic nervous and renin angiotensin aldosterone systems, and enhanced proinflammatory pathways. Most clinical trials have addressed the underlying condition rather than venous hypertension per se. Interpreting the effects of therapeutic interventions on renal venous congestion are therefore problematic because of such confounders as changes in left ventricular function, cardiac output, and blood pressure. Nevertheless, there is preliminary evidence from small studies of intense medical therapy or extracorporeal ultrafiltration for heart failure that there can be changes to central venous pressure that correlate inversely with renal function, independently from the cardiac index. Larger more rigorous trials are needed to definitively establish under what circumstances conventional pharmacologic or ultrafiltration goals might best be directed toward central venous pressures rather than left ventricular or cardiac output parameters. [Copyright &y& Elsevier]