Chronic Renocardiac Syndrome Research Articles

Eplerenone improves hyperglycemia and sympathetic excitation in chronic renocardiac syndrome in rats.

We aimed to assess the efficacy of eplerenone, a steroidal mineralocorticoid receptor antagonist known to reduce blood pressure and mitigate cardiovascular disease (CVD) progression, in retarding the progression of chronic kidney disease (CKD) and CVD in a rat model of type 4 cardiorenal syndrome (CRS). We grouped rats into four experimental categories: sham surgery, sham treatment with eplerenone, nephrectomy without eplerenone (Nx), and nephrectomy with eplerenone (Nx + EP). For the Nx + EP group, rats received five-sixths nephrectomy, inducing CKD and CVD conditions such as renal hypertension and hyperglycemia, and were then treated with eplerenone (100mg/kg/day, orally) over 4weeks after an initial 4-week observation period. Heart rate, blood pressure, blood sugar levels, and sympathetic nerve excitation were monitored biweekly. In addition, assessments of renal and cardiac tissues, including evaluation of renal tubulointerstitial injury, glomerular injury, and cardiomyocyte hypertrophy, were conducted at week 8. Eplerenone administration mitigated CKD and CVD progression in the Nx + EP group, evident by improved blood pressure (217.3 ± 5.4 versus 175.3 ± 5.6), blood sugar (121.8 ± 1.3 versus 145.6 ± 6.0) level, reduced sympathetic nerve excitation, and cardiomyocyte hypertrophy compared to the Nx group. However, renal tubulointerstitial injury, glomerular injury, and cardiovascular dysfunction, which were increased in rats with type 4 CRS, did not show significant changes with eplerenone treatment. Our study demonstrated that eplerenone treatment did not exacerbate type 4 CRS but improved blood pressure, blood sugar levels, sympathetic nerve excitation, and cardiomyocyte hypertrophy in this model.

Cardiovascular Alterations and Structural Changes in the Setting of Chronic Kidney Disease: a Review of Cardiorenal Syndrome Type 4.

Cardiovascular and renal physiology are interrelated. More than a decade ago this was codified in guidelines defining the five subtypes of the cardiorenal syndrome. Morbidity and mortality for those with the cardiorenal syndrome is high compared to demographically matched individuals without cardiorenal disease, acute or chronic. The focus of this review will be the epidemiology, the impact of chronic kidney disease on cardiac structure and function, and associated clinical symptoms, outcomes, and potential treatments for patients with chronic reno-cardiac syndrome, or cardiorenal syndrome type 4. Cardiac structural changes can be profound and are described in detail both at a cellular and physiologic level. Integrating therapies for the treatment of causative or resulting comorbidities may ultimately slow progression of both cardiac and renal disease as well as minimize symptoms and death.

71-Year-Old Man With a New Heart Murmur

71-Year-Old Man With a New Heart Murmur

Heart failure correction in patients with chronic renocardiac syndrome

Abstract Funding Acknowledgements Type of funding sources: None. In case of inadequate diagnosis and correction of the basic disease, which triggers the development of chronic heart failure (CHF), left ventricular (LV) remodeling leads to myocardial dysfunction and decompensation. Patients who entered the study EUCLID, demonstrated nephroprotective effect of lisinopril, which reduces the appearance of microalbuminuria. Target Study the effectiveness of lisinopril in the correction of CHF in patients with chronic renocardiac syndrome based on a study of LV diastolic function. Methods 59 patients with chronic renocardiac syndrome were investigated. All patients received lisinopril 10-20 mg per day. LV diastolic function was evaluated for Acuson Sequoia-512 before and after treatment. Results Changes in the kinetics of myocardial contractility were characterized by high amplitude of the interventricular septum, increased by 20%, end-systolic contractility index by 9.1%, the degree of shortening of the left ventricular size by 11.4%. A significant decrease in the rate of diastolic filling by passive relaxation (E) of 23.4% and a filling rate due to atrial contraction (A) at 20%. Violation of intracardiac hemodynamics as manifested by increasing the restrictive properties of the myocardium, as well as reducing the effectiveness of time and deceleration rate of early LV filling flow by 23.2 and 27.4%, increase and decrease of LV filling time active by reducing atrial 49.9% . Decreased as the time of isovolumic LV relaxation of the heart. During treatment with lisinopril was an increase in ejection fraction (EF) of 16.4% (p=0.004) or 53.2% (49.1, 58.9) to 61.9% (53.4, 68.0 ). The rate of mitral filling period of relaxation (Ve) increased from 0.53 m/s (0.43, 0.58) to 0.56 m/s (90.47, 0.63), or 5.7 % (p=0.039), while maintaining the diastolic filling due to atrial contraction. This has led to the restructuring of diastolic filling of the normal type, which was confirmed by the change of the reflectance upwards: Ratio of Ve/Va to treatment was 1.45 units. (1.02, 1.63), vand during treatment - 1.58 units (1.21, 1.90), or a 9.0% increase (p = 0.013). Equally, there was a decrease IVRT: from 61.9 ms (54.6, 78.8) to 56.4 ms (50.3, 72.4) or 8.9% (p=0.044). Conclusions Improvement of LV diastolic function is due to improved myocardial relaxation. ACE inhibitor (lisinopril), as a means of LV remodeling, reduce the degree of diastolic dysfunction by improving myocardial relaxation in patients with chronic renocardiac syndrome.

Chronic Secondary Cardiorenal Syndrome: The Sixth Innovative Subtype.

Heart failure, as the leading cause of cardiovascular death, has seen an increased prevalence nowadays, along with renal insufficiency. It's estimated that 25–63% of heart failure patients have the comorbidity of renal insufficiency, an independent risk factor of various cardiovascular events and predictors of poor prognosis (1). A therapeutic principle of heart failure emphasizing decongestive treatment is limited by the demand for sufficient perfusion in terms of renal insufficiency therapy, making the treatment of both concomitant diseases more complicated and contradictory, with mild balance; hence, the great interest in cardiorenal interactions has broadened among researchers and clinicians, and the concept of cardiorenal syndrome (CRS) was first proposed in 2004. CRS, defined as a pathophysiological process of adverse interaction between the heart and kidneys, encompasses a spectrum of diseases involving acute or chronic dysfunction in one organ that induces decompensated dysfunction in the other, and eventually they evolve into an interrelated and vicious cycle of declining function in both organs. CRS was first categorized into five subtypes in 2008 based on sequential organ involvement and the course of progression over time (i.e., acute or chronic), including acute cardiorenal syndrome, chronic cardiorenal syndrome, and acute renocardiac syndrome, chronic renocardiac syndrome, secondary cardiorenal syndrome, of which a brief definition, etiology, and pathophysiology are given in Table 1 (2). With the consideration that the previous secondary CRS subtype has a shortcoming in that it is not as symmetrical as the first four subtypes, as well as the huge difference of pathophysiological changes, the treatment principles of the two organs, and of gradually increasing in-depth knowledge of fibrosis pathogenesis over the past few years, it's become quite necessary to propose a new CRS classification. And that's why we now first propose the sixth innovative CRS subtype on the basis of the concept of “chronic co-impairment” of the heart and kidneys, further classifying traditional secondary CRS as acute secondary CRS and chronic secondary CRS, thus making the novel six kinds of CRS categories paired and matched correspondingly. The most common precipitant of acute secondary CRS is biotoxin damage and a cytokine storm generated by acute sepsis, and the primary treatment principles are cause-related treatment as aggressive anti-infective therapy, as well as symptomatic treatment of cardiac and renal dysfunction. However, the novel type 6 CRS (chronic secondary CRS) is actually more prevalent in clinical practice, and its pathophysiological and clinical characteristics as well as diagnosis and treatment principles vary dramatically from other subtypes of CRS, which will be described in detail in the following article. Table 1 New classification of CRS based on disease acuity and sequential organ involvement.

Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction

Background/Aims: Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Rats with adenine-induced chronic renal failure (ACRF) develop severe renal insufficiency and metabolic abnormalities that closely resemble those in patients with uremia. The aim of the present study was to determine left ventricular (LV) morphology and function in rats with ACRF. Methods: Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls, C). After 9-13 weeks animals were anesthetized with isoflurane and cardiac function was assessed both by echocardiography and by LV catheterization. Results: Rats with ACRF showed increases in serum creatinine (323±107 vs. 33±5 µM, P< 0.05), mean arterial pressure (115±6 vs. 106±7 mmHg, P< 0.05) and LV weight (3.4±0.3 vs. 2.5±0.2 mg/kg, P< 0.05) vs. controls. Rats with ACRF had reduced early diastolic tissue Doppler velocities in the LV, enlarged left atrial diameter (4.8±0.8 vs. 3.5±0.4 mm, P< 0.05) and elevated LV end-diastolic pressure (15±5 vs. 8±1 mmHg, P< 0.01). Cardiac output was increased in ACRF rats (211±66 vs. 149±24 ml/min, P< 0.05) and systolic function preserved. In the LV of ACRF rats there were statistically significant (P< 0.05) increases in cardiomyocyte diameter, proliferation and apoptosis, while there was no difference between groups in fibrosis. Conclusion: Rats with ACRF develop LV hypertrophy and diastolic dysfunction while systolic performance was preserved. There was an increased hypertrophy and apoptosis of cardiomyocytes in the LV of ACRF rats. The cardiac abnormalities in ACRF rats resemble those in patients with CKD in which heart failure with preserved ejection fraction is common. Hence, this experimental model is well suited for studying pathophysiological mechanisms in chronic renocardiac syndromes.

HUMORAL IMMUNITY TO THE DAMAGE OF LIPID METABOLISM IN PATIENTS WITH RENOCARDIAC SYNDROME

A total of 289 patients with chronic renocardiac syndrome, 204 of them with chronic glomerulonephritis and 85 diabetic nephropathy. The worsening of the lipid metabolism, depending on the degree of chronic renal failure (CRF), I noted in the degree of CKD, manifested increased low density lipoprotein (LDL) of 1.22 times (p=0.004), triglycerides (p=0.02), atherogenicity index (p&lt;0.0001) and decreased high-density lipoprotein (HDL) cholesterol (p&lt;0.001). The coefficient of LDL / HDL ratio was greatest in patients with CRF I, which indicates the most intense pro-atherogenic processes in these patients. The biological role of education lipoprotein immune complexes (LPIC) is confirmed by us revealed a statistically significant negative correlation between the ratio and the atherogenic LDL IgG (r=- 0,3; p=0.04), and LDL atherogenic factor IgM (r=-0,46, p=0.01) in patients with chronic renal failure group 1. A statistically significant negative correlation between daily proteinuria and LDL IgG, LDL IgM (r=-0,3; p=0,005; r=-0,4; p=0.004, respectively), which suggests the assumption of our damaging effect LPIC on the renal glomerulus.

Targeting multiple pathways reduces renal and cardiac fibrosis in rats with subtotal nephrectomy followed by coronary ligation.

Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney. Rats were subjected to subtotal nephrectomy followed 9weeks later by coronary artery ligation. From week 11 until week 16, rats received vehicle or losartan, or a combination of the NF-kB inhibitor PDTC, the NO donor molsidomine and superoxide dismutase mimetic tempol, or a combination of all four of these plus metoprolol together. At week 16, renal and cardiac structure, function and gene expression were assessed. Individual and combined treatments were similarly effective in limiting cardiac fibrosis and further decline in systolic function. Combined treatment with all five drugs reduced renal fibrosis and CTGF gene expression more effectively than other strategies. Combining all five drugs reduced heart rate, inotropy and mean arterial pressure (MAP). Thus, in our model of chronic renocardiac syndrome, combined treatments similarly decreased cardiac fibrosis and stabilized systolic function as losartan alone, perhaps suggesting a dominant role for a single factor such as angiotensin II type 1 (AT1) receptor activation or inflammation in the network of aberrant systems in the heart. However, tubulointerstitial fibrosis was most effectively reduced by a five-drug regimen, pointing to additive effects of multiple pathophysiological pathways in the kidney.

Role of Bile Acid-Regulated Nuclear Receptor FXR and G Protein-Coupled Receptor TGR5 in Regulation of Cardiorenal Syndrome (Cardiovascular Disease and Chronic Kidney Disease).

It is well known that chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease. In fact, studies have shown that cardiovascular event rates and all-cause mortality increase as a function of CKD as determined by decrease in estimated glomerular filtration rate and presence of microalbuminuria.1,2 In recent years, the term cardiorenal syndrome (CRS) has been proposed to define the relationship between cardiac disease and renal disease. Ronco et al has defined CRS as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other.3–6 CRS Type 1: acute CRS is defined as sudden worsening of cardiac function (acute cardiogenic shock or acutely decompensated heart failure), leading to acute kidney injury. CRS Type 2: chronic CRS is defined as chronic abnormalities in cardiac function (chronic congestive heart failure) causing progressive and potentially permanent CKD. CRS Type 3: acute renocardiac syndrome is defined as sudden worsening of kidney function (acute kidney injury or acute glomerulonephritis) causing acute cardiac disorder (heart failure, arrhythmia, or ischemia). CRS Type 4: chronic renocardiac syndrome is defined as CKD contributing to decreased cardiac function, cardiac hypertrophy, and increased risk of adverse cardiovascular events. CRS Type 5: secondary CRS is defined as systemic condition (obesity, diabetes mellitus, sepsis) causing simultaneous cardiac and renal dysfunction. In this review, I will be discussing mainly the type 5 CRS associated with obesity and diabetes mellitus and models of atherosclerosis and vascular calcification. In addition to discussing renal disease, I will also be discussing vascular disease because vascular dysfunction is a well-characterized complication of renal disease, and vascular dysfunction is also a leading cause of cardiac disease. Our work early on determined an important role for altered renal lipid …

Neuronal Nitric Oxide Synthase-Dependent Amelioration of Diastolic Dysfunction in Rats with Chronic Renocardiac Syndrome

We have recently described the chronic renocardiac syndrome (CRCS) in rats with renal failure, cardiac dysfunction and low nitric oxide (NO) availability by combining subtotal nephrectomy and transient low-dose NO synthase (NOS) inhibition. Cardiac gene expression of the neuronal isoform of NOS (nNOS) was induced. Hence, we studied the role of nNOS, in vivo cardiac function and β-adrenergic response in our CRCS model by micromanometer/conductance catheter. Left ventricular (LV) hemodynamics were studied during administration of dobutamine (dobu), the highly specific irreversible inhibitor of nNOS <smlcap>L</smlcap>-VNIO [<smlcap>L</smlcap>-N5-(1-Imino-3-butenyl)-ornithine], or both at steady state and during preload reduction. Rats with CRCS showed LV systolic dysfunction at baseline, together with prolonged diastolic relaxation and rightward shift of the end-systolic pressure-volume relationships. After <smlcap>L</smlcap>-VNIO infusion, diastolic relaxation of CRCS rats further prolonged. The time constant of active relaxation (tau) increased by 25 ± 6% from baseline (p < 0.05), and the maximal rate of pressure decrease was 36 ± 7% slower (p < 0.001). These variables did not change in controls. In our CRCS model, nNOS did not seem to affect systolic dysfunction. In summary, in this model of CRCS, blockade of nNOS further worsens diastolic dysfunction and <smlcap>L</smlcap>-VNIO does not influence inherent contractility and the response to dobu stress.

L'ipertrofia ventricolare sinistra nei pazienti affetti da malattia renale cronica

La patologia cardiovascolare rappresenta la principale causa di mortalità e morbidità nei pazienti affetti da malattia renale cronica (CKD) e malattia renale cronica terminale (ESRD). La patogenesi della malattia cardiovascolare in corso di nefropatia è multifattoriale e coinvolge fattori di rischio tradizionali e fattori di rischio collegati alla malattia renale. Come ormai universalmente accettato, l'interessamento cardiaco in corso di malattia renale cronica rientra nella cosiddetta Sindrome cardio-renale di tipo 4, la cosiddetta cardiopatia uremica caratterizzata, in primo luogo, dalla presenza di ipertrofia ventricolare sinistra, disfunzione sistodiastolica del ventricolo sinistro e, negli stadi terminali, scompenso cardiaco congestizio e cardiomiopatia dilatativa. La diagnosi di ipertrofia ventricolare sinistra (IVS) è affidata da un lato alle tecniche ecocardiografiche 2D e 3D e, dall'altra, a tecniche di imaging più sofisticate, come la risonanza magnetica cardiaca (CMRI). Scopo della review è quello di effettuare un excursus riguardante l'epidemiologia, la fisiopatologia e la diagnosi dell'ipertrofia ventricolare sinistra nei pazienti affetti da malattia renale cronica. (Cardionephrology)

Left Ventricular Hypertrophy in Patients with Chronic Kidney Disease

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias, and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Their pathogenesis relates to the close linkage between heart and kidneys and involves both traditional and non-traditional risk factors. According to the well-established classification of cardio-renal syndrome, the cardiovascular involvement in chronic kidney disease is known as “type 4 cardiorenal syndrome” (chronic renocardiac syndrome). Uremic cardiopathy is mainly characterized by both left ventricular systolic and diastolic impairment, often associated to right heart dysfunction due to the presence of a vascular access for hemodialysis. The typical clinical picture is represented by left ventricular hypertrophy (LVH), the pathogenesis of which is multifactorial and closely linked to elevated blood pressure, vascular stiffness and atherosclerosis. The diagnosis is mainly made by ultrasound (2D and 3D echocardiography) and cardiac magnetic resonance imaging (CMRI), although echocardiography is most widely employed since it is non-invasive and cheaper than CMRI. The following chapter provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of left ventricular hypertrophy in CKD patients.&nbsp;(Cardionephrology)

Abstract 18065: The Upregulation of MicroRNA miR-21 Mediates Concentric Left Ventricle Remodeling in a Rat Model of Chronic Renocardiac Syndrome

Chronic kidney disease (CKD) puts patients at a greatly increased risk of cardiovascular disease in a condition termed chronic renocardiac syndrome (RCS). We have utilized the 5/6 nephrectomy (5/6 NX) model in Sprague Dawley rats to study the gradual development of cardiac dysfunction resulting from declining kidney function. Previously, we identified alterations in several microRNAs (miRNAs) in left ventricle (LV) tissue 7 weeks after 5/6 NX surgery. We hypothesized that the upregulation of miR-21 in the LV following 5/6 NX contributes to LV pathology, rather than being a consequence of it. In situ hybridization revealed that miR-21 expression in the LV of 5/6 NX animals is highest in regions of perivascular fibrosis. To study the impact of miR-21 on LV remodeling and function, we delivered locked-nucleic acid (LNA) modified anti-miR-21 or anti-scrambled-miR (Exiqon, delivered i.v. at 1 mg/kg) to 5/6 NX animals (n=6/group) in 3 sequential days at 1 week post-surgery, and again 4 weeks post-surgery. Echocardiography was performed prior to 5/6 NX surgery and bi-weekly thereafter, throughout the 7 week study, to evaluate remodeling and function (anti-miR-21 vs. anti-scramble treated for all comparisons). The average LV miR-21 expression was reduced nearly 12-fold with anti-miR-21 treatment when measured 7 weeks post-5/6 NX. Anti-miR-21 treatment preserved stroke volume and fractional shortening between weeks 3 and 5 post-5/6 NX while both functional indices declined in anti-scramble treated rats. Additionally, concentric LV remodeling (LV wall hypertrophy and reduced chamber diameter) 5 weeks post-5/6 NX was completely prevented with anti-miR-21 treatment. At 7 weeks post-5/6 NX, when LV decompensation is evident in untreated rats, anti-miR-21 treatment maintained LV wall thickness and chamber diameter while fractional shortening was significantly increased (p &lt;0.05). Anti-miR-21 treatment had no effect on blood pressure. We conclude that chronic knockdown of miR-21 in the 5/6 NX model prevented pathological concentric remodeling. Together these data suggest that the upregulation of cardiac miR-21 following 5/6 NX is an important mediator of pathological cardiac remodeling and dysfunction.

Cardiorenal syndromes

Cardiac and kidney diseases are very common, and increasingly coexist. Classification for cardiorenal syndrome and for its specific subtypes has been developed and published recently by a consensus group of the Acute Dialysis Quality Initiative. Cardiorenal syndromes have been classified according to whether the impairment of each organ is primary, secondary or whether heart and kidney dysfunction occurs simultaneously as a systemic disease. The different syndromes were classified into five subtypes. Type-1: acute cardiorenal syndrome: an abrupt worsening of cardiac function leading to acute kidney injury and/or dysfunction. Type-2: chronic cardiorenal syndrome: chronic abnormalities in cardiac function causing kidney injury and/or dysfunction. Type-3: acute renocardiac syndrome: abrupt worsening of kidney function leading to heart injury and/or dysfunction. Type-4: chronic renocardiac syndrome: chronic kidney diseases leading to heart injury, disease and/or dysfunction. Type-5: secondary cardiorenal syndrome: acute or chronic systemic diseases leading to simultaneous injury and/or dysfunction of heart and kidney. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help cardiologists, nephrologists and physicians working on intensive care units to characterize groups of their patients with cardiac and renal impairment and to provide a more accurate treatment for them.

Cardio-renal cachexia syndromes (CRCS): pathophysiological foundations of a vicious pathological circle.

Cardio-renal syndromes (CRS) are defined as disorders of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. CRS have been classified into five categories, where types 2 and 4 represent respectively chronic cardio-renal and chronic reno-cardiac syndromes. In these conditions, the chronic disorder of either the heart or kidney has been shown to induce some degree of cachexia. At the same time, cachexia has been proposed as a possible mechanism contributing to the worsening of such pathological organ cross talk. Common pathogenetic mechanisms underlie body wasting in cachectic states of different chronic heart and kidney diseases. In these circumstances, a vicious circle could arise, in which cachexia associated with either heart failure or chronic kidney disease may contribute to further damage of the other organ. In chronic CRS, activation of the immune and neuroendocrine systems contributes to the genesis of cachexia, which in turn can negatively affect the heart and kidney function. In patients with cardiac sustained activation of the immune and neuroendocrine systems and oxidative stress, renal vascular resistance can increase and therefore impair renal perfusion, leading to worsening kidney function. Similarly, in renal cachexia, increased levels of pro-inflammatory cytokines can cause progressive left ventricular systolic dysfunction, myocardial cell death, endothelial dysfunction and increased myocardial fibrosis, with consequent impairment of the chronic reno-cardiac syndrome type 4. Thus, we speculate that the occurrence of different types of chronic CRS could represent a fundamental step in the genesis of cachexia, being renal and cardiac dysfunction closely related to the occurrence of systemic disorders leading to a final common pathway. Therefore, the heart and kidney and cachexia represent a triad causing a vicious circle that increases mortality and morbidity: In such circumstances, we may plausibly talk about cardio-renal cachexia syndrome. Complex interrelations may explain the transition from CRS to cachexia and from cachexia to CRS. Identification of the exact mechanisms occurring in these conditions could potentially help in preventing and treating this deadly combination.

Epoxyeicosatrienoic acids – Novel mechanism and pharmacological therapy of chronic renocardiac syndrome

Cardiorenal syndromes were defined and classified recently, but the mechanism of chronic renocardiac syndrome remains disputed. Theories about chronic renocardiac syndrome cannot offer a convincing explanation for it. As a result, the current therapies of chronic renocardiac syndrome do not contribute to a satisfied prognosis. Epoxyeicosatrienoic acids, the products of arachidonic acid metabolized by cytochrome P450 enzymes, play an important role in the maintenance of renal hemodynamics, and regulation of renal, cardiac, and vascular function with antihypertensive and anti-inflammatory properties. It is well documented that down-regulation of epoxyeicosatrienoic acids might be involved in alterations in various pathophysiological states, including hypertension, uremia and hepatorenal syndrome. Likewise, epoxyeicosatrienoic acids were reduced in heart failure and renal dysfunction. This leads to the proposed hypothesis that epoxyeicosatrienoic acids down-regulation may be the novel mechanism of chronic renocardiac syndrome. These findings suggest that manipulation of epoxyeicosatrienoic acid levels could be a novel pharmacological therapy strategy for chronic renocardiac syndrome.

Cardiorenal syndrome type 4-cardiovascular disease in patients with chronic kidney disease: epidemiology, pathogenesis, and management.

The term cardiorenal syndrome refers to the interaction between the heart and the kidney in disease and encompasses five distinct types according to the initial site affected and the acute or chronic nature of the injury. Type 4, or chronic renocardiac syndrome, involves the features of chronic renal disease (CKD) leading to cardiovascular injury. There is sufficient epidemiologic evidence linking CKD with increased cardiovascular morbidity and mortality. The underlying pathophysiology goes beyond the highly prevalent traditional cardiovascular risk burden affecting renal patients. It involves CKD-related factors, which lead to cardiac and vascular pathology, mainly left ventricular hypertrophy, myocardial fibrosis, and vascular calcification. Risk management should consider both traditional and CKD-related factors, while therapeutic interventions, apart from appearing underutilized, still await further confirmation from large trials.

ADPKD: Prototype of Cardiorenal Syndrome Type 4

The cardiorenal syndrome type 4 (Chronic Renocardiac Syndrome) is characterized by a condition of primary chronic kidney disease (CKD) that leads to an impairment of the cardiac function, ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. Clinically, it is very difficult to distinguish between CRS type 2 (Chronic Cardiorenal Syndrome) and CRS type 4 (Chronic Renocardiac Syndrome) because often it is not clear whether the primary cause of the syndrome depends on the heart or the kidney. Autosomal dominant polycystic kidney disease (ADPKD), a genetic disease that causes CKD, could be viewed as an ideal prototype of CRS type 4 because it is certain that the primary cause of cardiorenal syndrome is the kidney disease. In this paper, we will briefly review the epidemiology of ADPKD, conventional and novel biomarkers which may be useful in following the disease process, and prevention and treatment strategies.

Cardiorenal Risk Factors

The chronic renocardiac syndrome, in which chronic kidney disease (CKD) contributes to impairment of cardiac function or structure, is associated with an increased risk of adverse cardiovascular events. The prevalence of CKD in the U.S. population is approximately 11% and has been increasing over time. Numerous studies have demonstrated an association of CKD, defined by the presence of reduced glomerular filtration rate and/or albuminuria with adverse cardiovascular and renal outcomes. These data suggest that both albuminuria and glomerular filtration rate, which can be performed with minimally increased costs, should be included in the assessment of risk stratification for individual patients, in addition to traditional cardiovascular risk factors.

ADQI 7: the clinical management of the Cardio-Renal syndromes: work group statements from the 7th ADQI consensus conference

Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients.