Managing acute renal failure in patients with acute decompensated heart failure: The cardiorenal syndrome

In patients with acute decompensated heart failure, worsening renal function during conventional decongestive therapy (cardiorenal syndrome) affects prognosis and the initiation of therapies with known benefit in chronic heart failure. Potential strategies for decongestion in patients who develop cardiorenal syndrome include invasive hemodynamic monitoring to guide therapy, use of continuous diuretic infusions, ultrafiltration, or novel therapy with adenosine or vasopressin receptor antagonists. Clinical trials by the National Heart, Lung, and Blood Institute’s Heart Failure Network are currently underway to validate such therapies in patients with acute decompensated heart failure with worsening renal function and to establish novel biomarkers for the early identification of patients who develop cardiorenal syndrome.     

Cardiorenal Syndrome and the Role of Ultrafiltration in Heart Failure

Acute decompensated heart failure (ADHF) with associated volume overload is the most common cause of hospitalization in heart failure patients. When accompanied by worsening renal function, it is described as a cardiorenal syndrome and is a therapeutic challenge. Initial treatment commonly encompasses intravenous diuretics however, suboptimal results and high rehospitalization rates have led experts to search for alternative therapeutic strategies. Recent technological advances in extracorporeal therapies have made ultrafiltration a feasible option for treatment of hypervolemia in ADHF. Recent large randomized trials have compared the efficacy and safety of ultrafiltration with diuretics. Additionally, the benefits of novel pharmacologic approaches, including combining hypertonic saline with diuretics, have recently been studied. The aim of this review is to discuss the developments in both pharmacologic and extracorporeal methods for treating hypervolemia in ADHF and acute cardiorenal syndrome.     

Dialyse- und Ultrafiltrationsverfahren bei kardiorenalem Syndrom

Renal failure is common in patients with severe heart failure and this complex pathophysiological interaction is classified as cardiorenal syndrome. In these patients hydropic decompensation is the main reason for hospitalization. In patients with refractory heart failure characterized by diuretic resistance and congestion due to volume overload, ultrafiltration has to be considered. In cases of acute decompensated heart failure with deterioration of renal function, extracorporeal ultrafiltration is the preferred treatment modality. On the other hand, patients suffering from chronic decompensated heart failure, particularly patients with ascites, will profit from the treatment-specific advantages of peritoneal ultrafiltration. A prerequisite for an optimized care of patients with cardiorenal syndrome is the close collaboration between intensive care physicians, cardiologists and nephrologists.     

ROSE-AHF and Lessons Learned

Nesiritide and dopamine have been recognized for some time as potential renal adjunct therapies in the management of patients with acute heart failure (AHF). Several studies have yielded conflicting evidence of the efficacy of both medications in enhancing the renal function of patients with AHF. The Renal Optimization Strategies Evaluation (ROSE) study was a multicenter double-blind placebo controlled trial designed to assess the potential renoprotective effects of low-dose nesiritide and dopamine in AHF patients with renal dysfunction. This article will focus on previous research, summary of results, and lessons learned from the ROSE-AHF trial as well as future directions for clinical research and applications.     

Cardiorenal syndrome: A literature review

The incidence of cardiorenal syndrome is increasing; however, its pathophysiology and effective management are still not well understood. For many years, diuretics have been the mainstay of treatment for cardiorenal syndrome, although a significant proportion of patients develop resistance to diuretics and even deteriorate while on diuretics. Trials on different ways to counteract diuretic resistance and newer treatment modalities, such as nesiritide, arginine vasopressin receptor antagonists, adenosine receptor antagonists and ultrafiltration, have shown promising results.     

Pharmacologic management of the cardiorenal syndrome in heart failure

Cardiorenal syndrome describes the impairment of renal function and associated diuretic resistance in patients with heart failure and clinically manifest volume overload. The pathophysiology of this syndrome is poorly understood, but appears to be caused by impairment of tubuloglomerular feedback, neurohormonal activation, and other factors and therapies used in the management of heart failure. Early diagnosis of the cardiorenal syndrome by way of markers of renal injury and function is critical for timely interventions that may attenuate progression. Many novel therapies have been evaluated in the cardiorenal syndrome setting, including agents that block key local factors (eg, adenosine A_I receptor antagonists), improve diuresis, aquaresis, and natriuresis, and augment natural vasodilator mechanisms to improve renal perfusion. Furthermore, device-based approaches such as ultrafiltration may also play an important therapeutic role.     

Is There Still a Role for Ultrafiltration in the Management of Acute Heart Failure? CARRESS and Beyond

The Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial was a prospective, randomized study comparing ultrafiltration versus pharmacological therapy in the treatment of acute decompensated heart failure (ADHF) complicated by cardiorenal syndrome Bart et al. (N Eng J Med 367:2296–2304, 1). The study found that ultrafiltration was inferior to pharmacological therapy, resulting in a significant increase in serum creatinine and serious adverse events while producing no significant difference in weight loss. The CARRESS trial calls into question the viability of ultrafiltration as a preferable treatment strategy in ADHF patients with cardiorenal syndrome.     

奈西立肽对高龄急性失代偿性心力衰竭患者心、肾相关指标的影响

目的 评价奈西立肽对高龄急性失代偿性心力衰竭患者心肾相关指标的影响.方法 入选80例高龄急性失代偿性心力衰竭患者,随机分为常规治疗组(n=40)和常规治疗+奈西立肽组(奈西立肽组,n=40).两组均接受抗心力衰竭常规治疗,奈西立肽组在常规治疗的基础上增加奈西立肽0.5～1.0 mg/d持续泵入,速度0.0075～0.0...     

The progressive cardiorenal syndrome in heart failure: Mechanisms and therapeutic insights

The cardiorenal syndrome refers to the interdependence of cardiocirculatory aberrations and renal dysfunction that signify a worsening in heart failure outcome. Biochemically, it appears covertly as an abnormality in renal function and when progressive, is manifested by symptom exacerbation and worsening renal impairment during application of therapy to ameliorate such symptoms. The pathways leading to these distinct impairments involve not only hemodynamic deterioration but also neurohormonal, inflammatory, and intrinsic renal mechanisms that produce this syndrome. Traditional therapy with diuretics typically worsens the cardiorenal syndrome, and vasodilator or inotropic therapy has not been shown to help either. New therapeutic avenues involving vasopressin antagonists, adenosine antagonists, and ultrafiltration are being investigated. In the absence of underlying primary renal parenchymal disease, mechanical ventricular assist devices or cardiac transplantation achieve reversal of the progressive cardiorenal syndrome, indicating the sentinel role of interrupting the cardiocirculatory aberrations that accompany this clinical manifestation.     

Cardiorenal rescue study in acute decompensated heart failure: rationale and design of CARRESS-HF, for the Heart Failure Clinical Research Network

BackgroundWorsening renal function is common among patients hospitalized for acute decompensated heart failure (ADHF). When this occurs, subsequent management decisions often pit the desire for effective decongestion against concerns about further worsening renal function. There are no evidence-based treatments or guidelines to assist in these difficult management decisions. Ultrafiltration is a potentially attractive alternative to loop diuretics for the management of fluid overload in patients with ADHF and worsening renal function.Methods and ResultsThe National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network designed a clinical trial to determine if ultrafiltration results in improved renal function and relief of congestion compared with stepped pharmacologic care when assessed 96 hours after randomization in patients with ADHF and cardiorenal syndrome. Enrollment began in June 2008. This paper describes the rationale and design of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF).ConclusionsTreating the signs and symptoms of congestion in ADHF is often complicated by worsening renal function. CARRESS-HF compares treatment strategies (ultrafiltration vs stepped pharmacologic care) for the management of worsening renal function in patients with ADHF. The results of the CARRESS-HF trial are expected to provide information and evidence as to the most appropriate approaches for treating this challenging patient population.     

The Acute Cardiorenal Syndrome Type I: Considerations on Physiology,Epidemiology, and Therapy

Acute cardiorenal syndrome, also known as cardiorenal syndrome type 1, is defined as an abrupt worsening of cardiac function that occurs in at least 30 % of patients with acute decompensated heart failure and can lead to the development of acute kidney injury. The changes in renal function that occur in this setting have variable prognostic implications, as both poorer and better outcomes have been reported when renal function worsens during treatment of heart failure decompensation. Furthermore, it remains unclear when worsening renal function is actually a manifestation of true acute kidney injury or simply an indicator of hemoconcentration. Given these gaps in the understanding of the significance of renal function changes in the setting of decompensated heart failure, it is not surprising that studies on the effects of available therapies, including diuretics, vasoactive drugs, and mechanical fluid removal have yielded inconsistent results. The purpose of this review is to analyze critically the current knowledge on the pathophysiology, epidemiology, prognosis, and treatment of acute cardiorenal syndrome.     

心肾综合征的临床研究进展

心肾综合征一词已广泛用于进行性充血性心力衰竭引起的肾功能下降。为了概括心脏与肾脏之间复杂的因果关系,心肾综合征分为5种临床亚型:Ⅰ型:急性心肾综合征;Ⅱ型:慢性心肾综合征;Ⅲ型:急性肾心综合征;Ⅳ型:慢性肾心综合征;Ⅴ型:继发性心肾综合征。心肾综合征是慢性肾功能不全和慢性心力衰竭中治疗的难题,现就心肾综合征近年来临床研究进展进行综述。     

Role of Adenosine Antagonism in the Cardiorenal Syndrome

Acute decompensated heart failure (ADHF), generally related to signs and symptoms of volume overload, is one the most common reasons for hospitalization in the United States. Recently, it has been observed that the majority of patients with ADHF have baseline renal dysfunction. Moreover, heart failure (HF) treatment is limited by worsening renal function despite persistent volume overload. This connection between HF and renal dysfunction has been termed the cardiorenal syndrome and has made treatment of patients with stable and unstable HF challenging. Selective adenosine A1 receptor antagonists are novel pharmacologic agents that are currently under development to treat volume overload in HF while protecting or possibly improving renal function. In this article, we review the cardiorenal syndrome, the role of adenosine in renal function, and emerging data regarding the safety and efficacy of adenosine A1 receptor antagonists in patients with advanced HF.     

Renal dysfunction in acute congestive heart failure: a common problem for cardiologists and nephrologists

The term acute heart failure (AHF) refers to a clinical syndrome with typical symptoms and signs, in which a structural or functional heart abnormality leads to defective oxygen delivery. The term cardiorenal syndrome has been proposed to outline the strict interplay between cardiac and renal function. In the setting of acute cardiac decompensation, acute kidney injury (AKI) is generally referred to as cardiorenal syndrome type 1. In this review, we summarize the fundamental pathophysiological aspects of both AHF and AHF-related AKI. We also review the latest therapeutic options, including both pharmacological ones, such as loop diuretics, potassium-sparing diuretics and vaptans, and non-pharmacological ones, such as ultrafiltration, and their impact on patients’ outcome. We discuss the pathophysiology of diuretic resistance, a common occurrence in these patients, reviewing the available strategies to treat it and highlighting how a close collaboration between cardiologists and nephrologists is frequently crucial for the management of this complication. Finally, we discuss three new promising non-pharmacological tools for the prevention of AHF recurrence, including two methods that exploit sympathetic denervation and one technique that acts by increasing vagal tone.     

Cardiorenal Syndrome: Diagnosis,Treatment, and Clinical Outcomes

The pathophysiologic interactions that link the heart and kidney are multiple and complex, and have been grouped under the umbrella term “cardiorenal syndrome.” In the setting of acute decompensated heart failure, worsening renal function has been directly associated with poor clinical prognosis and complicates treatment. However, the pathophysiology underlying acute cardiorenal syndrome remains incompletely understood and treatment options remain limited. Traditionally, the development of worsening renal function in acute decompensated heart failure has been attributed to renal arterial underfilling due to reduced cardiac output or intravascular volume depletion. However, increasing data have expanded our understanding of the roles that venous congestion and intra-abdominal pressure play in driving renal injury, with important implications for therapeutic management and the development of novel renal-sparing therapies.     

Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Our purpose was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure and baseline renal dysfunction. BACKGROUND: Although nesiritide is approved for the treatment of acute decompensated heart failure, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue. METHODS: Consecutive patients with acute decompensated heart failure and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive nesiritide (0.01 microg/kg/min with or without a 2-microg/kg bolus) or placebo (5% dextrose in water) for 48 h in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by > or =20% and change in serum creatinine. RESULTS: Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs. 75.5 years, respectively), blood pressure (123/64 vs. 125/64 mm Hg) and serum creatinine (1.82 vs. 1.86 mg/dl). There were no significant differences in the incidence of a 20% creatinine rise (23% vs. 25%) or in the change in serum creatinine (-0.05 vs. +0.05 mg/dl). There were no significant differences in the secondary end points of change in weight (-2.19 vs. -1.58 kg), intravenous furosemide (125 vs. 107 mg), discontinuation of the infusion due to hypotension (13% vs. 6%), or 30-day death/hospital readmission (33% vs. 25%). CONCLUSIONS: In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with acute decompensated heart failure. (BNP-CARDS trial; http://www.clinicaltrials.gov/ct/show/NCT00186329?order=1; NCT00186329).     

Diuretika bei kardiorenalen Syndromen

Cardiorenal syndromes are well-defined diseases of the heart and kidneys and five forms can be distinguished which are divided into acute and chronic, as well as primary cardiac and primary renal forms. Triggering and predisposing factors contribute to the development of acute renal failure. Diuretics are necessary and indispensible drugs in cases of fluid overload in acute cardiorenal syndromes. In acute decompensated heart failure diuretics are recommended for the symptomatic treatment of hyperhydration. A benefit of diuretics with respect to hard endpoints (e.g. cardiovascular events and mortality) has not been demonstrated in chronic heart failure and chronic cardiorenal syndromes. Loop diuretics, thiazide diuretics, potassium-sparing diuretics and vasopressin V2 antagonist are available with varying mechanisms and sites of action. The maximum recommended dose of diuretics depends on renal function. Major side effects include electrolyte disturbances (e.g. hypokalemia, hyponatremia and hypomagnesemia), disorders of acid-base balance, increased insulin resistance and ototoxicity. The use of diuretics in cases of renal failure reduces the chance of recovery of renal function. A sequential nephron blockade and/or transient ultrafiltration or renal replacement therapy (e.g. hemodialysis and peritoneal dialysis) might be of benefit in cardiorenal syndromes and resistance to conventional treatment but evidence from controlled studies is still lacking.     

Novel strategies: challenge loop diuretics and sodium management in heart failure--Part I

This is the first of a 2-part series. This article reviews the relationships among diuretics, neurohormonal activation, renal function, fluid and Na management, the cardiorenal syndrome, and heart failure. Part II will describe novel therapies based on these relationships, focusing particularly on vasopressin antagonists and treatment using hypertonic saline solution with high-dose loop diuretics. Heart failure (HF) is a complex hemodynamic disorder characterized by chronic and progressive pump failure and fluid accumulation. Diuretics are a vital component of symptomatic management, and enhancing diuretic response in the setting of diuretic resistance is therefore pivotal. In HF patients treated with diuretics, compensatory pathophysiologic mechanisms to maintain vascular resistance, such as nonosmotic stimulation of vasopressin secretion and activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, promote renal Na and water reabsorption. Thus, there remains a need to develop novel therapies for HF patients who are refractory to conventional medical treatment. The conflicting results of diuretic treatments in HF and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation have suggested novel and counterintuitive strategies, focusing primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and neurohormonal interference. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.     

Congestion as a Therapeutic Target in Acute Heart Failure Syndromes

This review begins by discussing the importance of clinical congestion as the dominant presenting manifestation of acute heart failure syndromes (AHFS). The pathophysiology of the cardiorenal syndrome is reviewed, including its relationship to the use of current therapy, that is, loop diuretics. The review then summarizes results from recent clinical trials evaluating therapy for AHFS, with a focus on those studies investigating ultrafiltration and vasopressin antagonists, and also, but more briefly, vasodilators and inotropic agents. Possible reasons for the success and failure of various therapeutic strategies directed at the congested state are discussed. The review concludes with recommendations for possible new strategies and specific investigations designed to benefit from the lessons learned from both the recent successful trials and the more numerous failures.