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Context Heart failure (HF) and chronic kidney disease (CKD) are associated with high morbidity and mortality, especially in combination, yet little is known about the impact of these conditions together on end-of-life care. Objectives Compare end-of-life care and advance care planning (ACP) documentation among patients with both HF and CKD to those with either condition. Methods We conducted a retrospective analysis of deceased patients (2010-2017) with HF and CKD (n = 1673), HF without CKD (n = 2671), and CKD without HF (n = 1706), excluding patients with cancer or dementia. We compared hospitalizations and intensive care unit (ICU) admissions in the last 30 days of life, hospital deaths, and ACP documentation >30 days before death. Results 39% of patients with HF and CKD were hospitalized and 33% were admitted to the ICU in the last 30 days vs. 30% and 28%, respectively, for HF, and 26% and 23% for CKD. Compared to patients with both conditions, those with only 1 were less likely to be admitted to the hospital [HF: adjusted odds ratio (aOR) 0.72, 95%CI 0.63-0.83; CKD: aOR 0.63, 95%CI 0.53-0.75] and ICU (HF: aOR 0.83, 95%CI 0.71-0.94; CKD: aOR 0.68, 95%CI 0.56-0.80) and less likely to have ACP documentation (aOR 0.53, 95%CI 0.47-0.61 and aOR 0.70, 95%CI 0.60-0.81). Conclusions Decedents with both HF and CKD had more ACP documentation and received more intensive end-of-life care than those with only 1 condition. These findings suggest that patients with co-existing HF and CKD may benefit from interventions to ensure care received aligns with their goals.

Cardiorenal syndrome I (CRS-1) denotes a state in which acute kidney injury occurs in the setting of acute heart failure (AHF). Isoproterenol (Iso) administration is widly used as an AHF model by transiently inducing extreme tachycardia, hypotension, and myocyte apoptosis and/or necrosis. To gain potential insights into renal manifestations of CRS-1, mice were subjected to the Iso-AHF model (50 mg Iso/kg), followed by renal functional and renal cortical assessments over 4 hours Iso induced acute azotemia (doubling of BUN, plasma creatinine) and significantly reduced renal plasma flow (prolonged plasma para-amino-hippurate clearance). Although no morphologic tubular injury was identified, marked increases in renal cortical 'stress markers' (NGAL, HO-1, IL-6, MCP-1 mRNAs) and oxidant stress (decreased glutathione, increased malondialdehyde) were observed. These changes were catalytic Fe dependent, given that the iron chelator desferrioxamine (DFO) significantly blunted, or completely reversed, these renal cortical abnormalities. Despite these acute changes, no lasting renal injury was observed (assessed over 3 days). To determine whether Iso directly impacts tubular cell integrity, cultured proximal tubule (HK-2) cells were exposed to Iso. Substantial Fe dependent cell injury (decreased MTT uptake), and Fe independent increases in HO-1/IL-6 mRNA expression were observed. We conclude that Iso-induced AHF is a useful reversible model of CRS-1. Despite its largely hemodynamic ('pre-renal') nature, Fe-mediated oxidative stress and pro-inflammatory reactions are induced. These arise, at least in part, from direct Iso- induced tubular cell toxicity, rather than simply being secondary to Iso-mediated hemodynamic events. Finally, Iso-triggered renal cytokine production can potentially contribute to 'organ cross talk' and a systemic pro-inflammatory state.

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.

Background The increase in intraabdominal pressure (IAP) has been correlated with increased creatinine levels in patients with heart failure with severely reduced left ventricular ejection fraction (HFrEF). However, IAP has not been examined in more stable patients or those with heart failure with preserved ejection fraction (HFpEF). Patients and method We conducted an observational, prospective descriptive study that measured the IAP of patients hospitalised for decompensated heart failure (HF). The sample was stratified according to left ventricular ejection fraction (LVEF), with a cut-off of 50%. The objective was to analyse the IAP, the baseline characteristics and degree of congestion using clinical ultrasonography and impedance audiometry. Results The study included 56 patients, 22 with HFrEF and 34 with HFpEF. The patients with HFrEF presented a higher prevalence of ischaemic heart disease (11% vs. 6%; p = 0.010) and chronic obstructive pulmonary disease/asthma (6% vs. 2%; p = 0.025). The IAP was higher in the patients with HFrEF (17.2 vs. 13.3 mmHg; p = 0.004), with no differences in renal function at admission according to the LVEF (CKD-EPI creatinine) (HFrEF 55.0 mL/min/1.73 m2 [32.6–83.6] vs. HFpEF 55.0 mL/min/1.73 m2 [44.0–74.9]; p = 0.485). The patients with HFrEF presented a more congestive profile determined through ultrasonography (inferior vena cava collapse [26% vs. 50%; p = 0.001]), impedance audiometry (total body water at admission, 46 L vs. 41 L; p = 0.052; and at 72 h, 50.2 L vs. 39.1 L; p = 0.038) and CA125 concentration (68 U/mL vs. 39 U/mL; p = 0.037). Conclusions During the decompensation episodes, the patients with HFrEF had a greater increase in IAP and a higher degree of systemic congestion.

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) constitute a high-risk phenotype with significant morbidity and mortality and poor prognosis. Multiple proinflammatory comorbid conditions influence the pathogenesis of HFpEF and CKD. Renal dysfunction in HFpEF is a consequence of the complex interplay between hemodynamic factors, systemic congestion, inflammation, endothelial dysfunction, and neurohormonal mechanisms. In contrast to heart failure with reduced ejection fraction, there is a dearth of effective targeted therapies for HFpEF. Tailoring study design toward the different phenotypes and delving into their pathophysiology may be fruitful in development of effective phenotype-specific targeted pharmaceutical therapies.

Most heart failure hospitalizations are due to volume overload; however, it is not easily evaluated by physical examination. Avoidance of diuresis in patients with fluid overload to avoid acute kidney injury increases morbidity in heart failure. We hypothesize that fractional excretion of urate can be used to guide diuresis. (Level of Difficulty: Advanced.), Central Illustration

Sacubitril/valsartan (Sac/Val), a combined angiotensin-II receptor blocker (Val) and neprilysin inhibitor (Sac) in a 1:1 molar ratio, was shown to decrease the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and reduced left ventricular (LV) ejection fraction. This study examined the effects of Sac/Val on LV structure, function, and bioenergetics, and on biomarkers of kidney injury and kidney function in dogs with experimental cardiorenal syndrome.Fourteen dogs with cardiorenal syndrome (coronary microembolization-induced HF and renal dysfunction) were randomized to 3 months Sac/Val therapy (100 mg once daily, n = 7) or no therapy (control, n = 7). LV ejection fraction and troponin-I, as well as biomarkers of kidney injury/function including serum creatinine and urinary kidney injury molecule-1 were measured before and at end of therapy and the change (treatment effect change) calculated. Mitochondrial function measures, including the maximum rate of adenosine triphosphate synthesis, were measured in isolated cardiomyocytes at end of therapy. In Sac/Val dogs, the change in ejection fraction increased compared with controls, 6.9 ± 1.4 vs 0.7 ± 0.6%, P.002, whereas change in troponin I decreased, -0.16 ± 0.03 vs -0.03 ± 0.02 ng/mL, P.001. Urinary change in kidney injury molecule 1 decreased in Sac/Val-treated dogs compared with controls, -17.2 ± 7.9 vs 7.7 ± 3.0 mg/mL, P.007, whereas the change in serum creatinine was not significantly different. Treatment with Sac/Val increased adenosine triphosphate synthesis compared with controls, 3240 ± 121 vs 986 ± 84 RLU/µg protein, P.05.In dogs with cardiorenal syndrome, Sac/Val improves LV systolic function, improves mitochondrial function and decreases biomarkers of heart and kidney injury. The results offer mechanistic insights into the benefits of Sac/Val in HF with compromised renal function.

International audience; Sodium-glucose cotransporter 2 inhibitors offer cardiovascular and renal benefits in patients with chronic kidney disease through not yet clearly defined mechanisms. Juni et al. showed that sodium-glucose cotransporter 2 inhibitor empagliflozin exposure in vitro can restore cardiomyocyte function by counteracting harmful effects of uremic serum on the endothelium-cardiomyocyte crosstalk between endothelial cells and cardiomyocytes. The author's findings improved our understanding of cardiovascular impairment in chronic kidney disease and provided new perspectives for the beneficial effects of sodium-glucose cotransporter 2 inhibitor 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.

Background Cardiorenal syndrome (CRS) is a major health burden worldwide in need of novel therapies, as current treatments remain suboptimal. The present study assessed the therapeutic potential of apoptosis signal-regulating kinase 1 (ASK1) inhibition in a rat model of CRS. Methods Adult male Sprague-Dawley rats underwent surgery for myocardial infarction (MI) (week 0) followed by 5/6 subtotal nephrectomy (STNx) at week 4 to induce to induce a combined model of heart and kidney dysfunction. At week 6, MI + STNx animals were randomized to receive either 0.5% carboxymethyl cellulose (Vehicle, n = 15, Sham = 10) or G226 (15 mg/kg daily, n = 11). Cardiac and renal function was assessed by echocardiography and glomerular filtration rate (GFR) respectively, prior to treatment at week 6 and endpoint (week 14). Haemodynamic measurements were determined at endpoint prior to tissue analysis. Results G226 treatment attenuated the absolute change in left ventricular (LV) fractional shortening and posterior wall thickness compared to Vehicle. G226 also attenuated the reduction in preload recruitable stroke work. Increased myocyte cross sectional area, cardiac interstitial fibrosis, immunoreactivity of cardiac collagen-I and III and cardiac TIMP-2 activation, were significantly reduced following G226 treatment. Although we did not observe improvement in GFR, G226 significantly reduced renal interstitial fibrosis, diminished renal collagen-I and -IV, kidney injury molecule-1 immunoreactivity as well as macrophage infiltration and SMAD2 phosphorylation. Conclusion Inhibition of ASK1 ameliorated LV dysfunction and diminished cardiac hypertrophy and cardiorenal fibrosis in a rat model of CRS. This suggests that ASK1 is a critical pathway with therapeutic potential in the CRS setting.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity display a number of pathophysiologic features that may render them more or less vulnerable to negative effects of decongestion on renal function, including greater right ventricular remodeling, plasma volume expansion, and pericardial restraint. We aimed to contrast the renal response to decongestion in obese compared to non-obese HFpEF METHODS AND RESULTS: NIH heart failure network studies that enrolled patients with acute decompensated HFpEF (EF≥50%) were included [DOSE, CARRESS, ROSE and ATHENA]. Obese HFpEF was defined as a body mass index (BMI) ≥30 kg/m(2). Compared to non-obese HFpEF (n=118), patients with obese HFpEF (n=214) were an average of 9 years younger (71 vs 80 years,0.5mg/dl) (9 vs 0%, p=0.002). CONCLUSION: Despite being nearly a decade younger, obese HFpEF patients experience greater deterioration in renal function during decongestion compared to non-obese HFpEF. Further study to elucidate the complex relationships between volume distribution, cardiorenal hemodynamics and adiposity in HFpEF are needed.

BACKGROUND: This study aimed to evaluate whether glomerular filtration rate (eGFR) during admission modifies the predictive value of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) in patients hospitalized for acute heart failure (AHF). METHODS: We retrospectively evaluated 4595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 2008 through October 2019. To investigate the effect of kidney function on the association of NT-proBNP and CA125 with 1-year mortality (all-cause and cardiovascular mortality), we stratified patients according to four eGFR categories

There is a high prevalence of renal dysfunction in patients undergoing transcatheter mitral valve repair (TMVr) for mitral regurgitation (MR) and this has been shown to be an independent risk facto...

Cardiorenal syndrome commonly refers to the collective dysfunction of heart and kidney resulting in a cascade of feedback mechanism causing damage to both the organs and is associated with adverse clinical outcomes. The pathophysiology of cardiorenal syndrome is complex, multifactorial, and dynamic. Improving the understanding of disease mechanisms will aid in developing targeted pharmacologic and nonpharmacologic therapies for the management of this syndrome. This article discusses the various mechanisms involved in the pathophysiology of the cardiorenal syndrome.

Aims The mechanisms underlying cardiorenal syndromes are complex and not fully understood; Fibrosis seems to be a primary driver of the diseases' pathophysiology. Spironolactone can reduce cardiac or renal fibrosis by inhibiting endothelial-mesenchymal transition (EndMT). Spironolactone protection may rely on activation of adenosine receptors, but the role of the adenosine A2A receptor (A2AR) is unclear. We hypothesize that spironolactone may modulate A2AR to suppress EndMT and reduce cardiorenal remodeling. Main methods A model of renal injury followed by heart failure was established by subcutaneous administration of isoprenaline (Iso) to rats. Assessment of cardiac and renal function, fibrosis, EndMT markers, adenosine and A2AR expression was performed. TGF-β was used to induce EndMT in primary human umbilical vein endothelial cells (HUVECs). Rats or cells were divided into four groups: those that treated with spironolactone alone or in combination with A2AR antagonist ZM241385 or neither, and compared to normal controls. Key findings Isoprenaline-treated rats exhibited cardiac and renal fibrosis, impaired cardiac and renal function, enhanced EndMT, and lower A2AR expression. Spironolactone significantly up-regulated A2AR expression and inhibited EndMT in vivo and in vitro. Moreover, spironolactone improved cardiorenal remodeling and reduced dysfunction. These changes were exacerbated by administration of ZM241385. Together, these findings show that spironolactone up-regulated A2AR to reduce EndMT and ameliorate cardiorenal fibrosis. Significance The anti-fibrotic effects of spironolactone may partly depend on the up-regulation of A2AR, and that A2AR might be a potential therapeutic target for the treatment of cardiorenal syndrome.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used to control pain, inflammation, and limit the cardinal signs of injury in humans. However, prolonged use of NSAIDs increases the risk of heart attack (myocardial infarction; MI) and the subsequent risk of heart and renal failure. The molecular and cellular mechanism of action for this adverse effect, particularly along the cardiorenal network, is incomplete. To define the mechanism, carprofen (CAP), an NSAID was administered at the dose of 5 mg/kg to C57BL/6 male mice for two weeks. After last dose of CAP treatment mice were subjected to permanent occlusion of coronary artery that induces irreversible cardiac remodeling while maintaining naive and MI-controls. After MI, cardiac pathology and dysfunction were confirmed, along with additional measurements of kidney function, histology, and injury markers, such as plasma creatinine. CAP treatment increased plasma creatinine levels and subsequently, myocardial structural disorganization increased. Kidney neutrophil gelatinase associated lipocalin (NGAL) and protein expression were increased post-MI. After two weeks CAP treatment, the expression of pyrogenic pro-inflammatory cytokines TNF-α and IL-1β were increased compared to non-CAP treated mice, indicative of amplified inflammatory response. There was also evidence that renal injury of both the post-CAP treatment controls and post-CAP MI were much greater than the non-CAP treated naïve controls, as serum creatinine and NGAL levels were elevated along with obvious structural impairment of the glomerulus. Therefore, CAP treatment tampers with the acute inflammatory response that promotes cardiorenal syndrome and non-resolving inflammation post-MI in acute heart failure.

The data reported in this article are related to the paper entitle “Stem cells transplantation positively modulates the heart-kidney cross talk in Cardiorenal Syndrome Type II” (Vescovo et al., 2019), which analyzed the impact of stem cells injection in cardiorenal syndrome type II. The dataset contains detailed information on apoptosis and cytokines milieu modification after injection of c-Kit–selected human amniotic fluid stem cells (hAFS) or rats vascular progenitor cells (rSVC-GFP group) in an experimental model of CRSII. The data can be useful for clarifying the paracrine effects exerted by the injected cells.

Background Cardiac chamber size was previously studied by echocardiography, among patients with progressive kidney disease only. We aimed to explore the relations between all heart chamber volumes as assessed by CT pulmonary angiography and renal function, throughout all ranges. Methods Using a novel technology for automatic four-chamber volumetric analysis, we analyzed CT pulmonary angiography results for 748 consecutive patients (between January 1 and December 31, 2014) without pulmonary embolism, and correlated the chamber volumes, indexed to body surface area, with the estimated glomerular filtration rates (eGFRs). Results After adjustment for age, all cardiac chamber volumes aside from that of the left ventricle inversely correlated with the eGFR. For every 10-unit decrease in eGFR, the volume indices of the left atrium, right atrium, and right ventricle were larger by 3.1%, 2.3%, and 1.5% (P 90 mL/min/1.73 m2. Conclusions A simple concomitant volumetric analysis of all four cardiac chambers by CT pulmonary angiography demonstrated that differences in volume correlate with renal function even within the normal range spectrum. The difference was most evident in the left atrium. This finding may be the first clue to evolving cardiorenal syndrome and may serve as a target for early therapeutic interventions. Trial Registry ClinicalTrials.gov ; Clinical Trials registration number (Helsinki Committee): 0603-15-TLV; URL: www.clinicaltrials.gov .

Chronic diseases of the heart and of the kidneys commonly coexist in individuals. Certainly combined and persistent heart and kidney failure can arise from a common pathologic insult, for example, as a consequence of poorly controlled hypertension or of severe diffuse arterial disease. However, strong evidence is emerging to suggest that cross talk exists between the heart and the kidney. Independent processes are set in motion when kidney function is chronically diminished, and these processes can have distinct adverse effects on the heart. The complex chronic heart condition that results from chronic kidney disease (CKD) has been termed cardiorenal syndrome type 4. This review will include an updated description of the cardiac morphology in patients who have CKD, an overview of the most likely CKD-sourced culprits for these cardiac changes, and the potential therapeutic strategies to limit cardiac complications in patients who have CKD.

It is well established that a large number of patients with acute decompensated heart failure present with various degrees of heart and kidney dysfunction usually primary disease of heart or kidney often involve dysfunction or injury to the other. The term cardiorenal syndrome increasingly had been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements and to stress the bidirectional nature of heart-kidney interactions, a new classification of the cardiorenal syndrome with 5 subtypes that reflect the pathophysiology, the time frame, and the nature of concomitant cardiac and renal dysfunction was proposed. Cardiorenal syndrome can generally be defined as a pathophysiological disorder of the heart and kidneys, in which acute or chronic dysfunction of one organ may induce acute or chronic dysfunction to the other. Although cardiorenal syndrome was usually referred to as acute kidney dysfunction following acute cardiac disease, it is now clearly established that impaired kidney function can have an adverse impact on cardiac function.

Background Cardiorenal syndrome includes numerous conditions affecting the heart and kidney, and is a strong predictor of cardiovascular mortality. Methods An analysis was performed on 157 consecutive patients admitted to the Coronary Care Unit of the Camilo Cienfuegos Hospital due to an ST-segment elevation myocardial infarction and heart failure, from January 2013 to December 2016. An analysis was made of the presence of cardiorenal syndrome and its relationship with epidemiological, clinical, and analytical variables, as well as complementary explorations. The relationship between cardiorenal syndrome and in-hospital mortality was assessed using binary logistical regression. Results A total of 52 (33.1%) patients had a cardiorenal syndrome. The haemoglobin level was lower in the group of patients with cardiorenal syndrome (117.2 ± 15.3 vs. 123.3 ± 15.1, p = 0.019), and in left ventricular ejection fraction (34.8 ± 8 vs. 43.2 ± 10.8). A positive correlation was found between the Killip class and the increase in serum creatinine after 48 h. The serum creatinine was associated with left ventricular ejection fraction (r = 0.166; p = 0.038). The multivariate analysis showed that cardiorenal syndrome was an independent predictor of in-hospital mortality when adjusted for a history of ischaemic heart disease, diabetes mellitus status, atrial fibrillation, ventricular arrhythmias, left ventricular ejection fraction, age and systolic blood pressure. Conclusion The presence of cardiorenal syndrome has an influence on the prognosis of patients who suffer a cardiorenal syndrome. Its detection could be useful in the risk stratification.

Left ventricular assist devices (LVADs) improve survival in patients with advanced heart failure. As LVAD use increases, so do the number of patients with LVADs who also have kidney disease. However, there are only sparse data on how best to care for these patients. This review provides an overview of LVAD principles and indications, including blood pressure assessment and criteria for receipt of both destination and bridge to transplantation LVADs. Following LVAD implantation, kidney function may improve in the short term, particularly if cardiorenal physiology was present; in the longer term, data remain limited. Individuals with glomerular filtration rates chronically 30mL/min/1.73m

Interactions of the heart and kidney provide basis for the cardiorenal syndrome, a condition in which failure of one organ (either the heart or the kidney) leads to, or exacerbates, failure of the other organ. This heterogeneous and complex clinical entity is linked to higher morbidity and mortality, thus, warranting identification of novel molecular biomarkers that can be implemented to early diagnosis of cardiorenal syndrome (CRS) patients and to predict their disease stage and clinical outcome. Here, we used a microarray dataset for the identification of key differentially expressed genes (DEGs). Initial analysis based on the cut off criteria [i.e., p -value 0.5] revealed 11 upregulated and 10 down-regulated DEGs. All these 21 DEGs were subjected to network analysis separately that showed 5 genes (ADRB2, DAB2, CX3CR1, DHRS9 and CCZ1B) in upregulated and 6 genes (FOS, FOSB, EGR1, ABCA1, DUSP1, and CXCL8) in downregulated network modules. Ten functionally enriched DEGs out of 11 were further subjected to determine the cardiorenal syndrome-specific miRNA-mRNA regulatory network. Finally, resulting 12 node network revealed 4 hub genes (DAB2: upregulated and FOS, EGR1, and CXCL8: downregulated) associated with 8 miRNAs (hsa-let-7b-5p, hsa-miR-17-5p, hsa-miR-147a, hsa-miR-16-5p, hsa-miR-129-2-3p, hsa-miR-124,3p, hsa-miR-20a-5p, and hsa-miR-429). In Feed-Forward Loop (FFL) analysis among these four hub genes, three namely DAB2, FOS and EGR1 showed their roles in regulation and inhibition. With the assumption of this disease candidate gene prioritization, we report that DAB2, FOS, EGR1 and CXCL8 may serve as robust biomarkers in CRS.

Introduction and objectives The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Methods Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4 mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72 hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72 hours, and b) renal function changes and major clinical events at 30 days. Results The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. Conclusions We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.

Purpose Right heart failure (RHF) is a crucial risk factor in the development of acute kidney injury. By decreasing the right-ventricular filling pressures and increasing cardiac output, right ventricular assist devices (RVAD) may prevent the development of cardiorenal syndrome. We report our institutional experience on the development of renal function and outcome after left ventricular assist device (LVAD) and temporary RVAD implantation in congestive heart failure patients. Methods We retrospectively reviewed the data of 72 consecutive patients who received a continuous-flow LVAD and temporary RVAD due to terminal heart failure at our center from 12/ 2001 and 12/ 2019. Mean age of patient population was 58 ± 12 years, with 86.1% of the patients being male. Sixty-three patients (87.5%) were able to be successfully weaned from temporary RVAD support. However, two patients (2.8%) required an RVAD to be re-implanted due to progressive RHF. Median time of temporary RVAD support was 13 days (4 - 90 days). Renal function was determined by the Modification of Diet in Renal Disease (MDRD)-derived glomerular filtration rates (GFR), and patients were categorized into two groups based on pre-implant GFR: (1) normal renal function, defined by GFR > 60 (n=29), and (2) impaired renal function, defined by GFR Results The patient group with impaired renal function (RF) experienced a significant improvement of GFR: GFR at time of implant to month six, 41.94 ± 11.37 to 65.21± 39.52 (p=0.003), and after one-year GFR improved from 41.94 ± 11.37 to 55.73 ± 23.22 (p=0.012). Post-implant renal replacement therapy was indicated in eighteen patients (41.86%) of the impaired RF group vs. ten patients (34.48%) in the normal RF group. Post-implant survival after LVAD and temporary RVAD support at one, six, and 12 months for GFR 60 group, 89.7%, 72.4% and 72.4%, respectively (p=0.576). Conclusion LVAD and temporary RVAD support improves renal function in patients with renal dysfunction prior to implantation. Our data indicates that impaired renal function prior to implantation does not guarantee a worsened outcome.

Introduction Portal venous gas is a rare finding in adults and is typically associated with underlying intestinal ischemia. Portal venous gas can be detected by a bedside point of care ultrasound (POCUS) examination in adult patients in critical care units (CCU). Findings include echogenic bubbles flowing centrifugally throughout the portal venous system. Case presentation We present the case of a 73-year-old female with advanced ischemic cardiomyopathy and cardiorenal syndrome who was managed in the CCU. She developed vague abdominal pain and respiratory depression requiring intubation and dialysis during her course of treatment in the CCU. Her findings were consistent with portal venous gas upon POCUS, prompting computed tomography of her abdomen and surgical consultation. She was ultimately found to have nonobstructive mesenteric ischemia. Clinical discussion PVG is an ominous radiological sign and reflects intestinal ischemia in up to 72% of cases. Acute mesenteric ischemia of the small bowel could be due to occlusive or nonocclusive obstruction of the arterial blood supply or obstruction of venous outflow. Nonocclusive obstruction accounts for 5% to 15% of patients with acute mesenteric ischemia. Conclusion With the increasing use of POCUS, critical care physicians should be aware of findings consistent with portal venous gas as a bedside tool for directing the treating physician toward an ominous diagnosis in patients with shock., Highlights • Portal vein gas detected by point-of-care ultrasound in situations of unidentified shock indicates a high likelihood of underlying intestinal ischemia. • Point-of-care ultrasound plays an important role in detecting the sources of surgical emergencies. • Nonobstructive mesenteric ischemia can present with nonspecific symptoms in critically ill patients, leading to a delay in diagnosis.

Cardiorenal syndrome (CRS) has not been well characterized in veterinary medicine, yet an accurate appreciation of the kidney and the cardiovascular system and their interactions may have practical clinical implications. A consensus for cardiovascular-renal axis disorders of dogs and cats was recently attempted. The outcome of patients with CRS is likely to improve with the increasing awareness and ability to identify and understand the pathophysiologic characteristics of CRS. The utilization of existing and emerging organ-specific biomarkers with greater sensitivities than conventional diagnostics forecast new opportunities to diagnose and manage cardiac disease.

The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies.

Longstanding hypertension ultimately leads to heart failure (HF), and, as a consequence most patients with HF have a history of hypertension. Conversely, absence of hypertension in middle age is associated with lower risks for incident HF across the remaining life course. Cardiac remodeling to a predominant pressure overload consists of diastolic dysfunction and concentric left ventricular (LV) hypertrophy. When pressure overload is sustained, diastolic dysfunction progresses, filling of the concentric remodeled LV decreases, and HF with preserved ejection fraction ensues. Diastolic dysfunction and HF with preserved ejection fraction are the most common cardiac complications of hypertension. The end stage of hypertensive heart disease results from pressure and volume overload and consists of dilated cardiomyopathy with both diastolic dysfunction and reduced ejection fraction. “Decapitated hypertension” is a term used to describe the decrease in blood pressure resulting from reduced pump function in HF. Progressive renal failure, another complication of longstanding hypertension, gives rise to the cardiorenal syndrome (HF and renal failure). The so-called Pickering syndrome, a clinical entity consisting of flash pulmonary edema and bilateral atheromatous renovascular disease, is a special form of the cardiorenal syndrome. Revascularization of renal arteries is the treatment of choice. Most antihypertensive drug classes when used as initial therapy decelerate the transition from hypertension to HF, although not all of them are equally efficacious. Low-dose, once-daily hydrochlorothiazide should be avoided, but long-acting thiazide-like diuretics chlorthalidone and indapamide seem to have an edge over other antihypertensive drugs in preventing HF.

Acute decompensated heart failure is a common cause of hospitalization with worsening kidney function or acute kidney injury often complicating the admission, which can result in further dysfunction of both systems in the form of a cardiorenal syndrome. Therapy in this arena has been largely empiric as rigorous clinical trial data to inform therapeutic choices are lacking. Here we review and discuss the available clinical evidence for common approaches to the management of this condition. A multidisciplinary approach to the care of patients with cardiorenal syndrome that relies on the experience of nephrologists and cardiologists to individualize treatment is critical given the paucity of rigorous clinical trial data.

Introduction The heart and the kidneys are tightly interlinked with each other. So, primary disorder of one of these organs often results in the secondary dysfunction of other. Such interactions play a vital role in the pathogenesis of a clinical entity called cardio-renal syndrome (CRS). CRS type 4 refers to the development of cardiac failure in the patients with CKD. Objectives To study the prevalence of various cardiac diseases in the patients with CKD and risk factors for it. Methods Eighty patients with CKD who were being treated at KIMS, Hubli, from 1st January 2015 to 30th June 2015 were selected. Clinical evaluation and relevant investigations including echocardiography were done. Results Mean age of study population was 43.50 ± 14.53 years. Heart failure with reduced ejection fraction (HFrEF) and Heart Failure with preserved ejection fraction (HFpEF) were present in 21 (26.25%) and 59 (73.75%) respectively. Left ventricular (LV) hypertrophy was present in 55(68.75%). Thus, the prevalence of CRS type 4 was 61 (76.25%). Pericardial effusion was present in 12 (15%). Complete heart block was present in 2 (2.5%). Pulmonary hypertension (PH) was present in 35 (43.75%). Mean central venous pressure (CVP) and interdialysis fluid retention were significantly greater among those with LV failure, compared to those without LV failure (p = 0.0002, p = 0.025 respectively). Mean hemoglobin was significantly lower among patients with LV failure, compared to those without LV failure (p = 0.032). Conclusion The prevalence of cardiorenal syndrome type 4 is substantially high in patients with CKD and carries adverse outcome in relation to patient management.

The syndrome of heart failure involves complex pathophysiologic mechanisms and is associated with extremely high-morbidity, mortality and economic costs. This growing global epidemic has diverse etiologies and is fundamentally characterized by dyshomeostasis between heart and kidneys, leading to development and progression of the cardiorenal syndrome. Excessive and sustained sympathoexcitation has emerged as a single prominent factor involved in the structural and functional dysfunction of multiple organ systems during this disease. Studies in experimental models of heart failure indicate that ablation of the renal nerves may help restore renal sodium and water equilibrium as well as the attenuation of adverse cardiac remodeling. With the recent development of minimally invasive endovascular renal denervation in humans, it is anticipated that this technology would become a novel and important paradigm shift in the management of heart failure.

Background Cardiorenal syndrome (CRS) is the association of heart failure (HF) and renal failure (RF). This association is poor in terms of prognosis. Purpose To determine the correlation between glomerular filtration rate (GFR) and left ventricular ejection fraction (LVEF), and their impact on death. Methods This cross-sectional study, by document analysis, was conducted from January 2016 to December 2017 in the departments of cardiology and nephrology at University Hospital of Brazzaville. We had included the patients with association HF and RF. Results One hundred and eighty-six patients, 105 men (56.5%) were included. The mean age was 58 ± 15.5 years (range: 17 to 90 years). The risk factors were: hypertension (n = 128, 68.8%), diabetes (n = 56, 30%) and alcoholism (n = 23, 12.4%). At admission, the mean serum creatinine level was 47.2 ± 55.5 mg/L (range 16 to 136) and the mean GFR was 24.5 ± 22.8 ml/min (range: 2.1 and 100). In echocardiography, mean LVEF was 47.8 ± 18.2% (range: 22 to 87). LVEF 100 mg/L (n = 9, 50%, OR 11.8, CI95% 4–35, P 100 mg/L was independent determinant of death (OR 10.7, 95% CI 2.3–44, P = 0.001). Conclusion The prognosis of CRS is poor because the direct relation of blood creatinine level and death. Indeed, due to the limited access to dialysis in our country, the overall care of patients remains difficult. The extension and implantation of dialysis centers in our country remain the major challenges.

The Acute Dialysis Quality Initiative consensus conference proposed a classification of cardiorenal syndrome (CRS), aiming for a better delineation of each subtype. Although the exact pathophysiology of type 4 CRS is not completely understood, the mechanisms involved are probably multifactorial. There is growing evidence that oxidative stress is a major connector in the development and progression of type 4 CRS. Giving its complexity, poor prognosis and increasing incidence, type 4 CRS is becoming a significant public health problem. Patients with chronic kidney disease are particularly predisposed to cardiac dysfunction, due to the high prevalence of traditional cardiovascular risk factors in this population, but the contribution of risk factors specific to chronic kidney disease should also be taken into account.Much remains to be elucidated about type 4 CRS: despite progress over the last decade, there are still significant questions regarding its pathophysiology and there is as yet no specific therapy. A better understanding of the mechanisms involved may provide potential targets for intervention.The present review will provide a brief description of the definition, epidemiology, diagnosis, prognosis, biomarkers and management strategies of type 4 CRS, and the pathophysiological mechanisms and risk factors presumably involved in its development will be particularly highlighted. Resumo: A definição e classificação de síndrome cardiorrenal foram avançadas pela conferência Acute Dialysis Quality Initiave, visando uma melhor compreensão acerca de cada subtipo desta patologia. Embora a fisiopatologia exata não esteja completamente definida, os mecanismos envolvidos na síndrome cardiorrenal tipo 4 são potencialmente multifatoriais. Há crescente evidência de que o stress oxidativo é um conector principal no desenvolvimento e progressão desta síndrome. Dada a sua complexidade, pior prognóstico e incidência crescente, a síndrome cardiorrenal tipo 4 tem vindo a tornar-se num importante problema de saúde pública. Os pacientes com doença renal crónica estão particularmente predispostos a desenvolver disfunção cardíaca, devido à elevada prevalência de fatores de risco cardiovasculares nesta população, mas a contribuição de fatores de risco específicos da doença renal crónica devem ser tidos em conta.Muito permanece por esclarecer acerca da síndrome cardiorrenal tipo 4: apesar do progresso ao longo da última década, persistem questões importantes relativamente à sua fisiopatologia e ainda não existe tratamento específico. É sublinhada a necessidade de elaborar recomendações científicas para a prevenção e estratégias terapêuticas eficazes para a síndrome cardiorrenal tipo 4, sendo que um conhecimento mais aprofundado acerca dos mecanismos envolvidos na síndrome cardiorrenal tipo 4 poderão conferir potenciais alvos de intervenção.A presente revisão irá focar-se na síndrome cardiorrenal tipo 4: a sua definição, epidemiologia, diagnóstico, prognóstico, biomarcadores e estratégias terapêuticas serão brevemente descritos, mas uma particular atenção será dada aos mecanismos fisiopatológicos e fatores de risco presumivelmente envolvidos nesta patologia. Keywords: Type 4 cardiorenal syndrome, Chronic kidney disease, Heart failure, Cardiovascular risk factors, End-stage renal disease, Neurohormonal activation, Oxidative stress, Palavras-chave: Síndrome cardiorrenal tipo 4, Doença renal crónica, Insuficiência cardíaca, Fatores de risco cardiovascular, Doença renal crónica terminal, Ativação neuro-hormonal, Stresse oxidativo

We investigated oxidative stress and RAAS biomarkers, as well as their association, in chronic heart failure (CHF) patients on optimized medical therapy, stratified by disease severity or by renal function. Since vitamin D has been shown to attenuate RAAS activation and oxidative stress, we further evaluated the relationship between vitamin D, RAAS and oxidative stress in CHF patients with or without renal impairment. Sixty CHF outpatients were included and stratified by disease severity or by renal function. We quantified urinary hydrogen peroxide, plasma and urinary isoprostanes, plasma total antioxidant status, urinary angiotensinogen (intrarenal RAAS activation biomarker) and plasma angiotensinogen, plasma renin and aldosterone concentration, serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin peptides, and serum total 25-hydroxyvitamin D (S-total 25(OH)D). Severe CHF patients had higher urinary isoprostanes (p = 0.002) and lower S-total 25(OH)D (p = 0.006) compared to mild-to-moderate patients, but no differences were observed for other redox or RAAS biomarkers. Patients with impaired renal function (iRF) had higher urinary angiotensinogen (p = 0.003) and lower S-total 25(OH)D (p = 0.028) compared to those with normal renal function (nRF), while no differences were observed for the remaining RAAS and redox parameters. Several positive correlations between oxidative stress and RAAS biomarkers were detected in iRF patients, while in patients with nRF these correlations were primarily inverse. In CHF-iRF patients, S-25(OD)D was inversely associated with urinary isoprostanes, which in turn were positively associated with plasma angiotensinogen and serum ACE. In conclusion, CHF patients with renal function impairment have increased intrarenal RAAS activation and lower vitamin D values and might benefit from the combination of RAAS blockers with vitamin D and/or antioxidants.

Background: Worsening renal function (WRF) often occurs during acute heart failure (AHF) and can portend adverse outcomes; therefore, early identification may help mitigate risk. Neutrophil...

This study clarified the characteristics of intrarenal Doppler ultrasonography (IRD) profiles and their prognostic implications in heart failure (HF).IRD can assess intrarenal hemodynamics.Initially, 224 patients with HF were prospectively enrolled; 151 inpatients were enrolled during hospitalization for HF, and 73 were outpatients in our institution. In IRD profiles of interlobar vessels, the arterial resistance index (RI), venous impedance index (VII), and intrarenal venous flow (IRVF) pattern were assessed. Patients were followed to evaluate the associations with 1-year prognosis. Primary endpoints included death from cardiovascular disease and unplanned hospitalization for HF.Finally, 217 patients with adequate IRD images were enrolled. IRD profiles were associated with conventional risk factors for HF. In particular, IRVF was associated with mean right atrial pressure (RAP); 3 IRVF patterns were stratified by RAP (in a continuous pattern: 5.4 ± 2.5; in a biphasic pattern: 9.5 ± 3.5; and in a monophasic pattern: 14.9 ± 4.3 mm Hg; p 0.001). In addition, the monophasic IRVF pattern had a poorer prognosis than the other patterns (log rank p 0.001), and prognosis was poorer for the biphasic pattern than for the continuous flow pattern (log rank p = 0.01). Multivariate Cox proportional hazard model analysis revealed that IRVF patterns were associated with the endpoints, independent of other HF risk factors.IRVF patterns, rather than RI, depended on RAP, suggesting a correlation with renal congestion. In addition, IRVF patterns strongly correlated with clinical outcomes independent of RAP and other risk factors and might provide additional information to stratify vulnerable HF patients.

Although the importance of congestion in the disease progression of heart failure has long been recognized [(1)][1], much has focused on how cardiac impairment can lead to renal dysfunction. Over the past decade, there is increasing recognition that the ability of the kidneys to compensate for fluid