Cardiorenal Interactions Research Articles

Prediction of Responder and Influence for Cardio-Renal Interaction by Tolvaptan in Patients with Chronic Heart Failure

Prediction of Responder and Influence for Cardio-Renal Interaction by Tolvaptan in Patients with Chronic Heart Failure

Impact of Central Venous Pressure on Cardiorenal Interactions in Adult Patients with Congenital Heart Disease after Biventricular Repair

Cardiorenal interactions adversely impact the prognosis in heart failure patients an effect which crucially involves increased central venous pressure (CVP). However, it is unclear whether the same pathophysiology operates in adults with congenital heart disease (CHD). The present study was designed to assess cardiorenal interactions in adults with CHD after biventricular repair. We measured the kidney length (KL, cm/m) and renal resistive index (RI) in 77 consecutive patients and 30 controls. We also measured hemodynamics, plasma B-type natriuretic peptide level, 24-hour creatinine clearance, and peak oxygen uptake in each patient. The CVP correlated with the KL (r = 0.44, P <.001) and the RI was greater in the patients (P <.0001). The high RI was independently determined by the CVP, aortic pressure, and cardiac index (P <.05-.001), and correlated with the 24-hour creatinine clearance (r = -0.30, P <.05). The RI correlated closely with the neurohumoral activations and peak oxygen uptake (|r| = 0.45-0.50, P <.0001), and the patients with a traditional criteria of high RI (≥0.70) had a higher incidence of cardiovascular events that required unscheduled hospitalization (hazard ratio = 2.78, 95% confidence interval 1.26-6.10, P <.05). Multivariate Cox model with the cutoff values of KL ≥68 cm/m and RI ≥0.74 revealed that a greater KL (hazard ratio = 4.03, 95% confidence interval 1.46-11.1, P <.01) as well as B-type natriuretic peptide (P <.001) independently predicted the events. Hemodynamics, especially a high CVP, independently predicted the enlarged kidney and abnormal intrarenal flow dynamics that are closely associated with heart failure severity and cardiovascular events in adults with CHD after biventricular repair.

Mineralocorticoid Receptor Antagonists and Cardiovascular Mortality in Patients With Atrial Fibrillation and Left Ventricular Dysfunction

Background— Patients with heart failure (HF) and atrial fibrillation (AF) may differ from the larger HF population with respect to comorbidities, including renal impairment and overall prognosis. Associated cardiorenal interactions may mitigate the effects of pharmacological agents. Our primary objective was to assess the impact of mineralocorticoid receptor antagonists on cardiovascular mortality in patients with AF and HF enrolled in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial. Methods and Results— All 1376 patients randomized in the AF-CHF trial were included. The median baseline creatinine was 105.2 (Q1 88.4, Q3 125.0) μmol/L, and the median estimated glomerular filtration rate was 62.3 (Q1 49.0, Q3 77.2) mL/min per 1.73 m 2 . The renal function was moderately or severely impaired (ie, estimated glomerular filtration rate &lt;60 mL/min per 1.73 m 2 ) in 46.5% of patients. In multivariable analyses, increased creatinine was associated with worsening HF but not mortality. Mineralocorticoid receptor antagonists were prescribed in 44.8% and were independently associated with a 1.4-fold increase in total mortality (hazard ratio, 1.4; 95% CI [1.1–1.8]; P =0.005) and a 1.4-fold increase in cardiovascular mortality (hazard ratio, 1.4; 95% CI [1.1–1.9]; P =0.009). This was driven by an increased incidence of sudden cardiac death (hazard ratio, 2.0; 95% CI [1.3, 3.0]; P =0.001). Conclusions— Renal dysfunction was highly prevalent in patients with AF and HF. Mineralocorticoid receptor antagonists were independently associated with an increased incidence of cardiovascular deaths, predominantly of presumed arrhythmic cause. Although these provocative findings merit prospective validation, they underscore the importance of careful monitoring of renal function and electrolytes in patients with AF and HF receiving mineralocorticoid receptor antagonists. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00597077.

Target organ cross talk in cardiorenal syndrome: animal models

The combination of chronic kidney disease (CKD) and heart failure (HF) is associated with an adverse prognosis. Although clinical studies hint at a specific bidirectional interaction between HF and CKD, insight into the pathogenesis of cardiorenal syndrome (CRS) remains limited. We review available evidence on cardiorenal interactions from animal models of CKD and HF and discuss several studies that employed a "double-hit" model to research organ cross talk between the heart and kidneys. Regarding cardiac changes in CKD models, parameters of cardiac remodeling are equivocal and cardiac systolic function generally remains preserved. Structural changes include hypertrophy, fibrosis, and microvasculopathy. In models of HF, data on renal pathology are mostly limited to functional hemodynamic changes. Most double-hit models were unable to show that combined renal and cardiac injury induces additive damage to both organs, perhaps because of the short study duration or absence of organ failure. Because of this lack of "dual-failure" models, we have developed two rat models of combined CKD and HF in which renal dysfunction induced by a subtotal nephrectomy preceded cardiac dysfunction. Cardiac dysfunction was induced either functionally by nitric oxide depletion or structurally by myocardial infarction. In both models, we found that cardiac remodeling and failure were worse in CKD rats compared with controls undergoing the same cardiac insult. Variables of renal damage, like glomerulosclerosis and proteinuria, were also further worsened by combined cardiorenal injury. These studies show that target organ cross talk does occur in CRS. These models may be useful for interventional studies in rats.

Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome

BackgroundRecently, much attention has been focused on cardio-renal interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is produced in the proximal tubule by renal hypoxia and oxidative stress, has been identified as a useful marker for diagnosis of acute kidney disease and a predictor of future events in chronic kidney disease. However, the clinical significance of U-L-FABP measurements in patients with acute coronary syndrome (ACS) has not been completely evaluated. Methods and resultsThis study included 50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and 13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other serum parameters were measured at admission and at 24h after percutaneous coronary intervention. ResultsU-L-FABP levels in patients with AMI were significantly higher (p=0.0019), than in control subjects, while patients with UAP did not exhibit such an increase. U-L-FABP levels at admission were positively correlated with brain natriuretic protein levels (p=0.001) and duration of hospitalization (p=0.025). At follow-up angiography, patients with restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels (p<0.0001) than those without restenosis. After a median follow-up of 42 months, U-L-FABP levels at second measurement in patients with major adverse cardiocerebrovascular events (MACCEs) were significantly higher than those in patients without MACCEs (p=0.028). After adjusting for confounding factors, high U-L-FABP levels at second measurement were found to be independent factors for MACCEs (p=0.019). ConclusionsThese data suggest that patients with ACS, especially those with AMI, have high U-L-FABP levels, and that U-L-FABP measurements may be useful in identifying high-risk patients for future cardiovascular events after ACS.

The cardiorenal link in advanced cirrhosis

A considerable number of patients with advanced cirrhosis develop a hepatorenal syndrome. The pathogenesis involves liver dysfunction, splanchnic vasodilatation, and activation of vasoconstrictive systems. There are now several observations that indicate a relation between the renal failure and impaired cardiac function in patients with advanced cirrhosis. Cirrhotic cardiomyopathy has been described as a condition with impaired contractile responsiveness to stress and altered diastolic relaxation. We propose a cardiorenal interaction in patients with advanced cirrhosis and renal dysfunction that refers to a condition where cardiac dysfunction in cirrhosis is a major determinant of kidney function and survival. Thus, the relation between cardiac dysfunction and renal insufficiency should be target for future studies and development of new treatments should focus on ameliorating the cardiac dysfunction.

The relationship between the heart and the kidney in acute heart failure: doubts of the cardiologist and the nephrologist's point of view

The pathophysiological interactions that link the heart and kidney in heart failure are multiple and complex. This issue constitutes one of the most vexing and difficult challenges facing cardiologists. In the setting of acute decompensated heart failure, worsening renal function has traditionally been directly associated with poor clinical prognosis and complicates treatment. In the last years, many reports suggest that worsening renal failure may represent the final common pathway of several mechanistically distinct processes, with different prognostic implications. In the clinical scenario, the clinical significance of transient worsening of renal function may be different as compared with irreversible or progressive renal failure. In addition, it can represent a relatively normal response to treatment-induced physiological derangements such as a reduction in renal perfusion and/or intravascular volume. We here focus on these highlights, with special reference to the diagnostic criteria of renal dysfunction and the management of fluid overload. Two expert nephrologists were asked to answer a few important clinical questions: how should renal dysfunction be recognized and monitored? Are there therapies to counteract it and when, and more importantly, for whom should be applied? Their answers serve as touchstones for cardiologists to provide better individualized care for their patients with acute heart failure. Only a multidisciplinary and collaborative management of cardio-renal interactions will help to mitigate the difficult day-to-day clinical practice and improve our understanding of this condition through a concerted and constructive approach.

The puzzle of kidney dysfunction in heart failure: an introduction

Heart failure and kidney disease often coexist, and each of the two conditions may lead to progression of the other. Kidney dysfunction is an independent prognostic factor in patients with either acute or chronic heart failure. Worsening renal function may be related with poorer outcomes as well. Multiple mechanisms are involved in the cardio-renal interaction, including hemodynamic abnormalities, neurohormonal and inflammatory activation, oxidative stress, anemia, and abnormalities in mineral and vitamin D metabolism. Serum creatinine has limitations for the assessment of kidney function in patients with heart failure as its short-term changes are dependent on hemodynamic changes and fluid status. New biomarkers of glomerular and tubular function might allow an earlier and more accurate detection of worsening renal function.

Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function

Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5–10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79 ± 8 ml/min), diastolic dysfunction (E/e′) (CD 26 ± 2 vs. CRD 50 ± 5) and left ventricular overload (LVEDP CD 10.8 ± 2.8 vs. CRD 21.6 ± 1.7 mmHg). Congestion in CRD was confirmed by increased lung and atrial weights, as well as exaggerated right ventricular hypertrophy. Absence of accelerated renal dysfunction, measured by increased proteinuria, was supported by absence of additional focal glomerulosclerosis or further decline of renal blood flow in CRD. Only advanced peripheral endothelial dysfunction, as found in CRD, appeared to correlate with both renal and cardiac dysfunction parameters. Thus, proteinuric rats with myocardial infarction showed accelerated cardiac but not renal dysfunction. As parameters mimic the cardiorenal syndrome, these rats may provide a clinically relevant model to study increased cardiovascular risk due to renal dysfunction. Peripheral endothelial dysfunction was the only parameter that correlated with both renal and cardiac dysfunction, which may indicate a mediating role in cardiorenal interaction.

Cardiorenal interaction during the acute phase of experimental &amp;lt;i&amp;gt;Trypanosoma cruzi&amp;lt;/i&amp;gt; infection: the influence of aldosterone and the AT1 receptor on mortality

Introduction: Trypanosoma cruzi infection is a serious public health problem in Latin America. Despite positive results from programs directed to the interruption of vectorial transmission, there are still millions of people infected, and a large number, at the risk of infection. Chagas disease is typically associated with cardiac complications, and chronic symptoms include heart failure and megaesophagus development. Objective: In this study, we aimed to evaluate the importance of the cardiorenal axis and renin-angiotensin-aldosterone system (RAAS) activation in experimental T.cruzi infection. We also evaluated the influence of aldosterone and the angiotensin II receptor type 1 (AT1R) on the mortality of infected mice. Methods: BALB/c mice infected with the Y strain of T.cruzi were treated with spironolactone or losartan. We assessed parasitemia, mortality, and renal and cardiac function by using non-invasive methods. Results: Our data show that AT1R promotes an important (and necessary) inotropic positive effect in the heart and minimizes acute kidney injury. Conversely, aldosterone increases the release of K+ and aggravates heart failure. It also has associated effects on the renal, cardiovascular, and cardiac electrical conduction systems. Consequently, the aldosterone antagonist reduced the mortality rate by 50%, whereas the AT1R antagonist increased it by 20%. Conclusions: The RAAS connects the cardiorenal systems, and its components differentially affect the mortality of animals experimentally infected by T.cruzi.

Hemodynamic Classifications of Acute Heart Failure and Their Clinical Application - An Update -

Acute heart failure (AHF) is classically defined by signs and symptoms related to elevated ventricular filling pressures. Regardless of precipitant, underlying etiology or ejection fraction, the vast majority of hospital admissions are the result of worsening chronic HF. For the acutely decompensated patient, 4 hemodynamic profiles, stratified by degree of congestion ("dry" or "wet") and adequacy of perfusion ("warm" or "cold") predict prognosis and guide therapy. Relief of congestion is the primary goal of AHF management. Loop diuretics remain the mainstay of AHF treatment, but new modalities such as veno-venous ultrafiltration are promising. For patients with evidence of hypoperfusion, vasoactive agents may be needed to facilitate diuresis. The decision to use vasodilators or inotropes is complex and the need for invasive hemodynamic monitoring is often determined by the individual patient's characteristics. Routine use of inotropes should be discouraged; however when used, the short-term hemodynamic benefits conferred by these agents must be balanced against their tendency to increase adverse events. Although these strategies are effective in alleviating symptoms in most patients, management dilemmas arise from cardiorenal interactions and limitations in effective novel therapies. Epidemiological studies continue to emphasize that AHF portends a poor prognosis. Further studies are needed to improve our understanding and outcomes in this growing patient population.

Organ-Specific Responses to Circulatory Disturbances in Heart Failure: New Insights

Recent studies have provided new insights into the pathophysiology of congestive heart failure. Organ-specific responses to circulatory disturbances may differ via a hypoperfusion state and a venous congestion state. The liver and the kidneys serve as a good example of a differential injury pattern based on the predominant circulatory insult. Cardiorenal syndrome appears to be a kidney-specific response to predominantly right-sided backward heart failure ("congestive state"), rather than forward heart failure. Despite significant progress in our understanding of cardiorenal interactions, there is no specific therapy for the cardiorenal syndrome, which is a marker of the severity of the heart failure state.

Clinical Characteristics and Outcomes of Patients With Improvement in Renal Function During the Treatment of Decompensated Heart Failure

Background In the setting of acute decompensated heart failure, worsening renal function (WRF) and improved renal function (IRF) have been associated with similar hemodynamic derangements and poor prognosis. Our aim was to further characterize IRF and its associated mortality risk. Methods and Results Consecutive patients with a discharge diagnosis of congestive heart failure at the Hospital of the University of Pennsylvania were reviewed. IRF was defined as a ≥20% improvement and WRF as a ≥20% deterioration in glomerular filtration rate. Overall, 903 patients met the eligibility criteria, with 31.4% experiencing IRF. Baseline venous congestion/right-side cardiac dysfunction was more common ( P ≤ .04) and volume of diuresis ( P = .003) was greater in patients with IRF. IRF was associated with a greater incidence of preadmission (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.6–6.7; P < .0001) and postdischarge (OR 1.8, 95% CI 1.2–2.7; P = .006) WRF. IRF was associated with increased mortality (adjusted hazard ratio 1.3, 95% CI, 1.1–1.7; P = .011), a finding largely restricted to patients with postdischarge recurrence of renal dysfunction ( P interaction = .038). Conclusions IRF is associated with significantly worsened survival and may represent the resolution of venous congestion–induced preadmission WRF. Unlike WRF, the renal dysfunction in IRF patients occurs independently from the confounding effects of acute decongestion and may provide incremental information for the study of cardiorenal interactions.

Animal models of cardiorenal syndrome: a review

The incidence of heart failure and renal failure is increasing and is associated with poor prognosis. Moreover, these conditions do often coexist and this coexistence results in worsened outcome. Various mechanisms have been proposed as an explanation of this interrelation, including changes in hemodynamics, endothelial dysfunction, inflammation, activation of renin-angiotensin-aldosterone system, and/or sympathetic nervous system. However, the exact mechanisms initializing and maintaining this interaction are still unknown. In many experimental studies on cardiac or renal dysfunction, the function of the other organ was either not addressed or the authors failed to show any decline in its function despite histological changes. There are few studies in which the dysfunction of both heart and kidney function has been described. In this review, we discuss animal models of combined cardiorenal dysfunction. We show that translation of the results from animal studies is limited, and there is a need for new and better models of the cardiorenal interaction to improve our understanding of this syndrome. Finally, we propose several requirements that a new animal model should meet to serve as a tool for studies on the cardiorenal syndrome.

Revisiting the cardio‐renal hypothesis: the pivotal role of the kidney in congestive heart failure

This editorial refers to ‘Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: The NGAL EvaLuation Along with B-type NaTriuretic Peptide in acutely decompensated heart failure (GALLANT) trial’ by A.S. Maisel et al., published in this issue on pages 846–851. Our conceptual understanding of heart failure over the past century evolves over two common themes. First, the ability to demonstrate the existence of a pathogenic process by a measurement or a physiological finding allows the formulation of a testable hypothesis. Second, the ability to alter the natural history through treatment approaches that target such a process provides validation of the concept. Long before we had bedside haemodynamic and imaging techniques, ‘congestive failure’ was considered to be a heterogeneous condition but largely attributed to the failure of the kidneys to receive adequate blood flow (the so-called ‘cardio-renal hypothesis’). 1 Diuretic therapy was the primary approach, and continues to be highly effective at relieving signs and symptoms. With the development of tools to measure intra-cardiac pressures and estimate cardiac efficiencies with calculated output values or increasingly sophisticated imaging techniques, the cardio-centric views placed the word ‘heart’ into congestive heart failure (‘cardiocirculatory hypothesis’). 2 This led to the widespread adoption of ‘ejection fraction’ as an important criterion for determining an underlying impairment in cardiac function, and put forward the promise of vasodilators and inotropic drugs to facilitate circulatory efficiency in the 1970s to 1980s. Next, advances in laboratory measurements recognized high levels of hormonal activation occurring in the setting of congestion and cardiac insufficiency (‘neurohormonal hypothesis’). It has led to the development of drugs that counteract both the major regulatory homeostatic hormones (renin-angiotensin2aldosterone and adrenergic systems), and the conduct of large-scale clinical trials to demonstrate their abilities to reduce adverse outcomes beyond haemodynamic improvement in the 1980s and 1990s. Better understanding of how to avert arrhythmogenic death and the ability to visualize electrical and mechanical dyssynchrony catalyzed technological development in device therapy with implantable defibrillators and cardiac resynchronization therapy in the 2000s. Today, patients with heart failure survive longer but with more co-morbid conditions, and yet their recurrent admissions to the hospital with congestion remain the single largest challenge to healthcare providers and to societal costs. The cardio-renal interaction has regained attention in recent years because common aetiologies of heart failure and kidney disease cannot fully explain the co-occurrence of these pathologies. 3 During decongestive treatment of acute decompensated heart failure, this interaction is even more complex and poorly understood. The often-encountered scenario is worsening of renal function during diuretic treatment (conveniently defined as a ≥0.3 mg/dL rise in serum creatinine), 4,5 forcing clinicians to hold off on diuretics while the patient is incompletely decongested. However, the presence of significant congestion itself is more predictive of the development of worsening renal function than impaired cardiac output, 6,7 even though in some cases the treatment to relieve congestion may result in improving (or at the least neutral) outcomes despite a rise in serum creatinine. 8‐10 Clearly, our bedside insights into the adequacy of the failing heart and/or kidneys to maintain euvolaemia and relieve congestion remain far from precise, and treatment strategies are yet to alter the natural history of the condition. In this issue, Maisel et al. 11 present their findings from a prospective, multi-centre study looking at the prognostic value of a novel biomarker, neutrophil gelatinase-associated lipocalin (NGAL), alone and in combination with B-type natriuretic peptide (BNP) in 186 patients with acute on chronic heart failure confirmed by the presence of an elevated BNP (.100 pg/mL). The investigators report higher plasma levels of NGAL and BNP in patients with events (30-day re-hospitalization or all-cause mortality) compared to patients with no events. They also display an array of statistical findings in an attempt to show that NGAL provides incremental value to standard prognostic measures, despite their acknowledgement of a relatively small event rate (16% or 29 deaths) with short follow-up. The lack of comprehensive description of patient characteristics, their serial changes of plasma NGAL, and treatment regimens over the course of hospitalization precluded more detailed understanding of how to best utilize this biomarker at

New roles for renin and prorenin in heart failure and cardiorenal crosstalk

The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure–associated morbidity and mortality remain high, especially in the presence of kidney disease. The effect of RAAS blockade may be limited due to the loss of an inhibitory feedback of angiotensin II on renin production. The subsequent increase in prorenin and renin may activate several alternative pathways. These include the recently discovered (pro-) renin receptor, angiotensin II escape via chymase and cathepsin, and the formation of various angiotensin subforms upstream from the blockade, including angiotensin 1–7, angiotensin III, and angiotensin IV. Recently, the direct renin inhibitor aliskiren has been proven effective in reducing plasma renin activity (PRA) and appears to provide additional (tissue) RAAS blockade on top of angiotensin-converting enzyme and angiotensin receptor blockers, underscoring the important role of renin, even (or more so) under adequate RAAS blockade. Reducing PRA however occurs at the expense of an increase plasma renin concentration (PRC). PRC may exert direct effects independent of PRA through the recently discovered (pro-) renin receptor. Additional novel possibilities to interfere in the RAAS, for instance using vitamin D receptor activation, as well as the increased knowledge on alternative pathways, have revived the question on how ideal RAAS-guided therapy should be implemented. Renin and prorenin are pivotal since these are at the base of all of these pathways.

Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome

Although inflammation is a physiologic response designed to protect us from infection, when unchecked and ongoing it may cause substantial harm. Both chronic heart failure (CHF) and chronic kidney disease (CKD) are known to cause elaboration of several pro-inflammatory mediators that can be detected at high concentrations in the tissues and blood stream. The biologic sources driving this chronic inflammatory state in CHF and CKD are not fully established. Traditional sources of inflammation include the heart and the kidneys which produce a wide range of pro-inflammatory cytokines in response to neurohormones and sympathetic activation. However, growing evidence suggests that non-traditional biomechanical mechanisms such as venous and tissue congestion due to volume overload are also important as they stimulate endotoxin absorption from the bowel and peripheral synthesis and release of pro-inflammatory mediators. Both during the chronic phase and, more rapidly, during acute exacerbations of CHF and CKD, inflammation and congestion appear to amplify each other resulting in a downward spiral of worsening cardiac, vascular, and renal functions that may negatively impact patients' outcome. Anti-inflammatory treatment strategies aimed at attenuating end organ damage and improving clinical prognosis in the cardiorenal syndrome have been disappointing to date. A new therapeutic paradigm may be needed, which involves different anti-inflammatory strategies for individual etiologies and stages of CHF and CKD. It may also include specific (short-term) anti-inflammatory treatments that counteract inflammation during the unsettled phases of clinical decompensation. Finally, it will require greater focus on volume overload as an increasingly significant source of systemic inflammation in the cardiorenal syndrome.

Dialysis-Induced Myocardial Stunning: The Other Side of the Cardiorenal Syndrome

Cardiorenal syndrome is an umbrella term describing the range of interactions between the heart and kidneys. Commonly, this focuses on the potential for reduced renal function as a consequence of heart disease and the impact of reduced renal functional reserve on the heart. Importantly, these interactions include both consequences of the disease state and those arising from therapeutic interventions directed at the cardiorenal axis. This article focuses on the potential impact of dialysis treatment, which generates intermittent circulatory stress and results in both acute and chronic adverse cardiovascular effects. This largely unappreciated dimension of the cardiorenal interaction in patients with end-stage renal failure is common, associated with a significant increase in mortality, and may be amenable to a variety of therapeutic approaches in this population characterized by particularly significant clinical management challenges.

A re-appraisal of volume status and renal function impairment in chronic heart failure: combined effects of pre-renal failure and venous congestion on renal function

The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least in the context of current treatment where possible reflex neurohumoral activation is ameliorated by the background treatment by blockers of the renin–angiotensin–aldosterone system.

El síndrome cardiorenal en insuficiencia cardíaca: Un paradigma en evolución

Heart failure constitutes a significant source of morbidity and mortality in the United Sta-tes and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associatedwith adverse clinical outcomes. This interaction, termed the cardiorenal syndrome, is a complex phe-nomenon characterized by a pathophysiological dise-quilibrium between the heart and the kidney, in which malfunction of one organ subsequently promotes the impairment of the other.Multiple neuro-humoral mechanisms are involved in this cardiorenal interaction, including the deficiency of and/or resistance to compensatory natriuretic pepti-des, leading to sodium retention, volume overload and organ remodeling. Management of patients with the cardiorenal syndrome can be challenging and should be individualized. Emerging therapies must address the function of both organs in order to secure better clinical outcomes. To this end, a multidisciplinary ap-proach is recommended to achieve optimal results.