Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.

Prognostic Factors in Cardiorenal Syndrome Type 1: Retrospective Observational and Analytical Study

Introduction: Type 1 cardiorenal syndrome (CRS 1) is characterized by acute impairment of cardiac function leading to acute renal dysfunction. CRS1 is present in 25% of patients admitted for heart failure. The objective of our study is to analyze the epidemiological, clinical, therapeutic profile and the risk and prognostic factors of these patients. Materials and Methods: We identified 120 patients with cardiorenal syndrome (CRS) over a one-year period to determine the prevalence and risk factors for developing CRS 1. We analyzed the clinical, biological, and evolutionary profiles of patients with CRS 1 and determined the risk factors for the occurrence of acute kidney injury (AKI) as well as the mortality factors in these patients. Résultats: The average age of our patients with CRS1 is 58 ± 9 years, with a sex ratio of 1.4. The average eGFR of our patients is 35 ± 6.5 ml/min/1.73m2. Diabetes was found in 17% of our patients and hypertension in 14%. The etiology of cardiac impairment is predominantly acute coronary syndrome (ACS), followed by rhythm disorders. Renally, all our patients have acute kidney injury (AKI), with 86% having functional acute renal failure and 14% having acute tubular necrosis. Therapeutically, 50% of our patients are on diuretics, 42% receive beta-blocker treatment, and RAAS blockers are used in 29% of cases. Renal replacement therapy (RRT) sessions were required in 13.8% of cases. In univariate analysis, male gender, tachyarrhythmia, and hypertension are associated with the early onset of acute kidney injury (AKI). The use of diuretics, anemia, and low left ventricular ejection fraction (LVEF) are linked to a higher risk of developing CRS 1 (p = 0.021, p = 0.037, p = 0.010 respectively). In multivariate analysis, advanced age is significantly associated with increased mortality risk in CRS 1 patients (p = 0.030), while beta-blocker use is considered a protective factor (p = 0.014). Conclusion: Our study identifies several key factors associated with outcomes in type 1 CRS. Male gender, tachyarrhythmia, and hypertension are linked to early-onset AKI. The use of diuretics and the presence of anemia increase the risk of developing CRS1. Advanced age is significantly associated with higher mortality rates. Conversely, the use of beta-blockers appears to be protective in this patient population. .

Impact of erythropoietin therapy on cardiorenal syndrome:A systematic review with meta-analysis

BACKGROUND Heart and kidney dysfunction frequently coexist in patients with acute heart failure due to the overlap between these two organ systems.Cardiorenal syndrome(CRS)results from pathology occurring in the heart and kidneys along with the consequences of dysfunction in one organ contributing to dysfunction in the other and vice versa.AIM To evaluate the use of erythropoietin(EPO)in patients with CRS and its effects on hemoglobin(Hb),major cardiovascular(CV)events,and hospitalization rates.METHODS On February 24,2022,searches were conducted using PubMed,MEDLINE,and EMBASE,and 148 articles were identified.A total of nine studies were considered in this systematic review.We assessed the included articles based on the National Heart,Lung,and Blood Institute quality assessment tools for controlled intervention and observational cohort or cross-sectional studies.An assessment of bias risk was conducted on the chosen studies,and data relevant to our review was extracted.RESULTS The systematic review of these studies concluded that most existing literature indicates that EPO improves baseline Hb levels and decreases myocardial remodeling and left ventricular dysfunction without reducing CV mortality.In addition,the effect of EPO on the hospitalization rate of patients with CRS needs to be further studied since this relationship is unknown.Future studies,such as randomized controlled clinical trials and prospective cohort studies,should be conducted to enhance the literature on the potential of EPO therapy in patients with CRS.CONCLUSION Our systematic review suggests that EPO therapy may have a significant role in managing CRS.The review highlights the potential benefits of EPO in improving baseline Hb levels,reducing the risk of major CV events,improving cardiac remodeling,myocardial function,New York Heart Association class,and B-type natriuretic peptide levels.However,the effect of EPO treatment on hospitalization remains unclear and needs further exploration.

Renal Profile of Patients with Cardiorenal Syndrome: Nephrology and Cardiology Department Experience of the University Hospital IBN SINA of Rabat

Introduction: Cardio-renal syndrome (CRS) is a complex pathophysiological entity affecting the heart and kidneys in which acute or chronic dysfunction of one organ can induce acute or chronic dysfunction of the other organ. Five types of CRS have been described. Methods: The study explored the prevalence and types of Cardiorenal Syndrome (CRS) at CHU Ibn Sina in Rabat. Over a year, 120 CRS patients were assessed, excluding those with end-stage chronic renal failure. We analyzed the epidemiological, clinical, therapeutic and evolutionary profile of these patients. Results: The average age of our patients is 67.8 ± 12 years, with extremes ranging from 39 years to 92 years. The sex ratio is 1.35. The different types of CRS types (1, 2, 4 and 5) were noted respectively in 28.4%, 20.8%, 5%, 45.8%, however, we did not note patients having CRS type 3. On the renal level, we noted acute renal failure (ARF) in 51.6% of patients, of whom 61.3% had functional ARF and 38.7% presented with acute tubular necrosis. Chronic renal failure (CRF) is found in 48.4% of cases, of which 39% are at stage III and 61% are at stage IV. The etiology of CKD is dominated by hypertensive nephropathy (72.4%) followed by diabetic nephropathy (60.3%). Therapeutically diuretics are administered in 51% of our patients. We used hemodialysis in 9.1% of patients who are resistant to diuretics. Vasoactive drugs are used in 9.5% of our patients. Mortality risk factors for patients with CRS are significantly related to advanced age, long hospital stay, type 1 CRS, re-hospitalization, acute pulmonary edema (APE), use of hemodialysis, right heart failure (RHF), valvulopathy and hemodynamic instability (OR = 1.15, p = 0.01;OR = 4.5, p = 0.03;OR = 5.2, p = 0.019;p Conclusion: CRS type 5 was most common, with hypertension and diabetes being primary causes of Chronic Kidney Disease. Mortality factors were linked to acute pulmonary edema, hemodialysis, right heart failure, valvulopathy, and re-hospitalization.

Fluid overload as a major target in management of cardiorenal syndrome:Implications for the practice of peritoneal dialysis

Congestion is an integral component of cardiorenal syn-drome and portends an adverse impact on the outcomes. Recent studies suggest that congestion has the ability ofmodulating the interactions between the kidney and the heart in this setting. Peritoneal dialysis （PD） is a home-based therapeutic modality that is not only offered to patients with end-stage renal disease to provide solute clearance and ultrafltration, but it has also been used in patients with refractory heart failure and fuid overload to help optimize volume status. Several uncontrolled studies and case series have so far evaluated the role of PD in management of hypervolemia for patients with heart failure. They have generally reported favorable results in this setting. However, the data on the outcomes of patients with end-stage renal disease and concomitant heart failure is mixed, and the proposed theoretical advantages of PD might not translate into improvedclinical endpoints. Congestion is prevalent in this patient population and has a signifcant effect on their survival. As studies suggest that a significant subset of patients with end-stage renal disease who receive PD therapy are hypervolemic, suboptimal management of congestion could at least in part explain these conficting results. PD is a highly fexible therapeutic modality and the choice oftechniques, regimens, and solutions can affect its ability for optimization of fluid status. This article provides an overview of the currently available data on the role and clinical relevance of congestion in patients with cardiorenal syndrome and reviews potential options to enhance decongestion in these patients.

Evidence based review of management of cardiorenal syndrome type 1

Cardiorenal syndrome(CRS)type 1 is the development of acute kidney injury in patients with acute decompensated heart failure.CRS often results in prolonged hospitalization,a higher rate of rehospitalization,high morbidity,and high mortality.The pathophysiology of CRS is complex and involves hemodynamic changes,neurohormonal activation,hypothalamic-pituitary stress reaction,inflammation,and infection.However,there is limited evidence or guideline in managing CRS type 1,and the established therapeutic strategies mainly target the symptomatic relief of heart failure.This review will discuss the strategies in the management of CRS type 1.Six clinical studies have been included in this review that include different treatment strategies such as nesiritide,dopamine,levosimendan,tolvaptan,dobutamine,and ultrafiltration.Treatment strategies for CRS type 1 are derived based on the current literature.Early recognition and treatment of CRS can improve the outcomes of the patients significantly.

Range of adiposity and cardiorenal syndrome

Obesity and obesity-related co-morbidities,diabetes mellitus,and hypertension are among the fastest-growing risk factors of heart failure and kidney disease worldwide.Obesity,which is not a unitary concept,or a static process,ranges from alterations in distribution to the amount of adiposity.Visceral adiposity,which includes intraabdominal visceral fat mass and ectopic fat deposition such as hepatic,cardiac,or renal,was robustly associated with a greater risk for cardiorenal morbidity than subcutaneous adiposity.In addition,morbid obesity has also demonstrated a negative effect on cardiac and renal functioning.The mechanisms by which adipose tissue is linked with the cardiorenal syndrome(CRS)are hemodynamic and mechanical changes,as well neurohumoral pathways such as insulin resistance,endothelial dysfunction,nitric oxide bioavailability,renin-angiotensin-aldosterone,oxidative stress,sympathetic nervous systems,natriuretic peptides,adipokines and inflammation.Adiposity and other associated co-morbidities induce adverse cardiac remodeling and interstitial fibrosis.Heart failure with preserved ejection fraction has been associated with obesity-related functional and structural abnormalities.Obesity might also impair kidney function through hyperfiltration,increased glomerular capillary wall tension,and podocyte dysfunction,which leads to tubulointerstitial fibrosis and loss of nephrons and,finally,chronic kidney disease.The development of new treatments with renal and cardiac effects in the context of type 2 diabetes,which improves mortality outcome,has highlighted the importance of CRS and its prevalence.Increased body fat triggers cellular,neurohumoral and metabolic pathways,which create a phenotype of the CRS with specific cellular and biochemical biomarkers.Obesity has become a single cardiorenal umbrella or type of cardiorenal metabolic syndrome.This review article provides a clinical overview of the available data on the relationship between a range of adiposity and CRS,the support for obesity as a single cardiorenal umbrella,and the most relevant studies on the recent therapeutic approaches.

Why do young people with chronic kidney disease die early?

Cardiovascular disease poses the greatest risk of premature death seen among patients with chronic kidney disease(CKD).Up to 50% of mortality risk in the dialysis population is attributable to cardiovascular disease and the largest relative excess mortality is observed in younger patients.In early CKD,occlusive thrombotic coronary disease is common,but those who survive to reach end-stage renal failure requiring dialysis are more prone to sudden death attributable mostly to sudden arrhythmic events and heart failure related to left ventricular hypertrophy,coronary vascular calcification and electrolyte disturbances.In this review,we discuss the basis of the interaction of traditional risk factors for cardiovascular disease with various pathological processes such as endothelial dysfunction,oxidative stress,low grade chronic inflammation,neurohormonal changes and vascular calcification and stiffness which account for the structural and functional cardiac changes that predispose to excess morbidity and mortality in young people with CKD.

Role of imaging in the evaluation of renal dysfunction in heart failure patients

Heart failure and kidney disease share common pathophysiological pathways which can lead to mutual dysfunction,known as cardiorenal syndrome.In heart failure patients,renal impairment is related to hemodynamic and nonhemodynamic factors.Both decreased renal blood flow and renal venous congestion due to heart failure could lead to impaired renal function.Kidney disease and worsening renal function are independently associated with poor prognosis in heart failure patients,both in acute and chronic clinical settings.The aim of this review is to assess the role of renal imaging modalities in the evaluation and management of heart failure patients.Renal imaging techniques could complete laboratory data,as estimated glomerular filtration rate,exploring different pathophysiological factors involved in kidney disease and adding valuable information about renal structure and function.In particular,Doppler examination of arterial and venous hemodynamics is a feasible and non invasive technique,which has proven to be a reliable method for prognostic stratification in patients with cardiorenal syndrome.The renal resistance index,a measure related to renal hemodynamics,can be calculated from the Doppler evaluation of arterial flow.Moreover,the analysis of Doppler venous flow patterns can integrate information from the arterial study and evaluate renal congestion.Other imaging modalities are promising,but still confined to research purposes.

Role of different kinds of dialysis in the treatment of refractory heart failure

Cardiorenal syndrome is a severe and potentially lethal disease in which heart and kidney failures coexist. The classic treatment with loop diuretics is ineffective due to the resistance of the kidney to those drugs, which requires the use of other therapies, such as extracorporeal ultrafiltration and peritoneal dialysis. This last technique is useful both in the acute treatment of acute heart decompensation and the chronic management of heart failure, because it improves heart function by reducing the volume overload, which in turn contributes to improving the kidney function with a limited number of side effects, which makes it the technique of choice for the treatment of diuretic-resistant heart failure. In this review, we present a description of the different kinds of cardiorenal syndrome, as well as the different treatments that are used, with special attention to the different modalities of peritoneal dialysis.

Cardiorenal syndrome： pathophysiological mechanism, preclinical models, novel contributors and potential therapies

Objective To review the current knowledge about the pathophysiological mechanisms,preclinical models,novel contributors and potential therapies of cardiorenal syndrome.Data sources The literature concerning cardioranal syndrome in this review was collected from PubMed published in English up to January 2014.Study selection Original articles and critical reviews related to cardiorenal syndrome were selected and carefully analyzed.Results Cardiorenal syndrome is a condition characterized by kidney and heart failure where failure of one organ worsens the function of the other thus further accelerating the progressive failure of both organs.The pathophysiology of cardiorenal syndrome is not fully understood,but may be caused by a complex combination of neurohormonal system activation,endothelial dysfunction,proteinuria,oxidative stress,uremic toxins and other factors.Managing cardiorenal syndrome is still a major therapeutic challenge in clinical practice because many of the drugs used to control heart failure can worsen renal function,and vice versa.Non-dialyzable uremic toxins,such as indoxyl sulfate,causing detrimental effects on the heart and kidney as well as stimulation of inflammatory responses,may be an effective therapeutic target for cardiorenal syndrome.Conclusions Suitable disease models of cardiorenal syndrome are urgently needed to investigate the pathophysiology and effective therapeutic approaches to the condition.Non-dialyzable protein-bound uremic toxins that may have cardiac and renal effects may provide therapeutic benefit to cardiorenal syndrome patients.

Gingerol improves cardiac function in rats with cardiorenal syndrome via inhibiting fibrosis

Background Cardiorenal syndrome(CRS)is a clinical syndrome with a complex mechanism,and there is currently no specific treatment.Gingerol was confirmed to possess anti-inflammatory,antioxidant and cardiotonic properties as cardiovascular pharmacological effects.However,in vivo studies have yet to prove that it can improve cardiac function and inhibit fibrosis in rats with cardiorenal syndrome.Methods In this study,34 male Sprague-Dawley(SD)rats were randomly divided into control(n=9),model(n=12)and gingerol groups(n=13).The model and the gingerol groups underwent ligation of the left anterior descending coronary artery and 5/6 subtotal nephrectomy to construct a type 2 cardiorenal syndrome rat model.The rats in gingerol group were injected intraperitoneally with 50 mg/kg gingerol.The same amount of saline was administered to both the control and the model groups.Following 4 weeks of treatment,the rat cardiac function and myocardial fibrosis were evaluated by cardiac ultrasound and blood biochemistry.Results Biochemical results showed that the brain natriuretic peptide(BNP)levels of gingerol group decreased(P<0.05).Cardiac ultrasound revealed that gingerol improved cardiac systolic function and ventricular remodeling(P<0.05).The systolic function of the model group was significantly decreased compared with the control group.Masson staining confirmed that the fibrosis area in the model group was significantly augmented than that in the control group,while the area of fibrosis in the gingerol group was diminished compared to the model group(P<0.01).Moreover,immunofluorescence showed that compared with the control group,the expression of collagen 1,TGF-β1 andα-SMA was significantly increased in the model group,and both collagen deposition and the expression of collagen I,TGF-β1 andα-SMA decreased in gingerol group.Immunohistochemistry revealed that the expression of collagen 1 andα-SMA was significantly increased in the model group compared with the control group,while it was decreased in gingerol group(P<0.05).Conclusions Gingerol can improve the cardiac function and cardiac fibrosis in rats with cardiorenal syndrome.

Rosuvastatin alleviates renal injury in cardiorenal syndrome model rats through anti-inflammatory and antioxidant pathways

Background:Cardiorenal syndrome is increasingly common and has been reported to be associated with inflammation and oxidative stress,and statins have anti-inflammatory and antioxidant effects.Therefore,we designed this experiment to study the preventive effect of statins on cardiorenal syndrome.The aim of the study is to investigate the effect of early rosuvastatin use on cardiorenal syndrome.Method:Forty-five Wistar rats were randomly divided into 3 groups.A unilateral nephrectomy group(Group 1),a unilateral nephrectomy+coronary ligation group(Group 2),and a unilateral nephrectomy+coronary ligation+rosuvastatin group(Group 3).Right kidney removal was performed on all rats during the first week,while Group 3 was given statin intragastric administration at 10 mg/kg/d.One month later,coronary ligation was performed on rats in Groups 2 and 3.Group 3 continued statin treatment.After feeding for 3 months and 2 days,the rats were killed;urine and blood were collected and sent to the laboratory for the determination of the urinary protein/creatinine ratio and blood lipid,creatinine,and urea nitrogen levels,respectively.Serum interleukin 1β,interleukin 6,malondialdehyde,glutathione peroxidase,angiotensin II,neutrophil gelatinase-associated lipocalin,cystatin C,and B natriuretic peptide levels were also determined.On the day before euthanasia,all rats were anesthetized and examined by cardiac ultrasound.Hematoxylin-eosin and periodic acid–Schiff staining were performed on heart and kidney sections.Results:The ejection fraction in Group 2 was lower than that in Group 1(P<0.01).The ejection fraction value in Group 3 was lower than that in Group 1(P<0.01).Interleukin-1βlevels in Group 2 were higher than those in Group 1(P<0.01).Interleukin-1βlevels in Group 3 were lower than those in Group 2(P<0.01).The malondialdehyde value in Group 3 was lower than that in Group 2(P<0.05).Histopathology showed that Group 1 had slight renal damage,renal injury was aggravated in Group 2,and renal injury was still present in Group 3,but with alleviated morphology.Conclusion:The interaction of the heart and kidneys in rats is related to inflammation and oxidation.Rosuvastatin can slow down the development of the heart-kidney interaction through anti-inflammatory and antioxidant effects.