Sindrome Cardiorenal: Perspectiva do Cardiologo

Introduction

It has become increasingly recognized by cardiologists and nephrologists that there are important bidirectional functional and pathological interactions between the heart and the kidney, wherein dysfunction of either organ promotes clinical worsening of the other. Cardiovascular disease constitutes a significant threat for patients with renal disease, and renal dysfunction is also often present in patients with cardiac disease. The clinical consequences of these interactions have gained attention and have prompted further definition, classification, and understanding of the relationship, and are the bases for the clinical entity termed cardiorenal syndrome (CRS) in human medicine. Cardiorenal syndrome has not been well characterized in veterinary medicine, but a recent attempt has been made to define a consensus for cardiovascular-renal disorders (CvRD) of the dog and cat.

A Definition

The definition of CRS includes a variety of acute or chronic conditions, where the primary failing organ can be the heart or the kidney, or both due to a systemic condition, and how the dysfunction of one organ system affects the function of the other organ system.

Classification

Five subtypes have been suggested in order to simplify the identification and the approach in the clinical setting.

Type 1 CRS - Acute cardiorenal syndrome is characterized by a rapid impairment of the cardiac function leading to acute kidney injury. There are multiple and complex mechanisms by which acute heart failure or an acute onset of chronic heart failure leads to acute kidney injury (AKI).

Type 2 CRS - Chronic cardiorenal syndrome consists of chronic cardiovascular disease causing progressive chronic kidney disease (CKD). Chronic heart failure (CHF) is likely to cause persistently reduced renal perfusion, chronic renal congestion ("congestive kidney failure"), and neurohormonal changes associated with chronic sympathetic stimulation (production of epinephrine, angiotensin, endothelin, and release of natriuretic peptides and nitric oxide).

Type 3 CRS - Acute renocardiac syndrome is characterized by an acute primary worsening of kidney function that leads to acute cardiac dysfunction. AKI can affect the cardiac function through multiple mechanisms, such as fluid overload, electrolyte disturbances, neurohormonal activation and myocardial depressant factors, potentially contributing to the development of arrhythmias, pericarditis and acute heart failure.

Type 4 CRS - Chronic renocardiac syndrome consists of primary chronic kidney disease that contributes to cardiac dysfunction. Decreased systolic function, left ventricular hypertrophy and a high output state (secondary to anemia) are some of the potential long-term cardiac sequelae of CKD.

Type 5 CRS - Secondary cardiorenal syndrome is characterized by cardiac and renal dysfunction secondary to an acute or chronic systemic condition. Sepsis is the most common acute condition that affects both the heart and the kidney. Diabetes mellitus and hyperadrenocorticism are typical chronic diseases in dogs that have a similar effect on the urinary and cardiovascular systems.

Table 1. Human and veterinary classification of cardiorenal syndrome

Classification of the heart disease, AKI and CKD is an important step to characterize the type of CRS. The recommended cardiac disease classification is the American College of Veterinary Internal Medicine (ACVIM) cardiac disease severity classification, which was adapted from the American College of Cardiology/American Heart Association classification system that uses an A through D categorization (Table 2). The International Renal Interest Society (IRIS) proposed AKI and CKD classifications, which are the most widely accepted in veterinary medicine.

Cardiac biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) are well established indicators of cardiac disease or injury. Identification of tubular biomarkers of early kidney injury, such as NGAL, clusterin and cystatin c, are crucial to the recognition of CRS and management of both conditions.

Table 2. ACVIM cardiac disease classification

Management of the Cardiorenal Patient

Cardiologists treat a significant number of patients with AKI and CKD, but there is no established protocol for the treatment of cardiovascular disorders in these patients. Patients with kidney dysfunction may receive a suboptimal treatment for concurrent cardiovascular conditions, even though they may benefit from the standard therapies. This may account for part of the worse prognosis attributed to patients with renal disease. CRS patients may benefit from co-management by cardiologists and nephrologists.

Angiotensin-converting enzyme inhibitors and angiotension-receptor blockers (ARBs) are beneficial in cardiovascular and renal diseases, but patients with renal dysfunction are less likely to receive this type of drugs due to the concern of worsening renal function. A better understanding of the relative risk of using these and other drugs may be very important in CRS patients.

Mineralocorticoid receptor antagonists (aldosterone blockers) have the potential for renal and cardiac protection, therefore the use of spironolactone in this subset of patients may be beneficial if the patients tolerate the drug.

Loop diuretics may have conflicting effects on the renal function. By reducing renal congestion they may improve GFR and delay the progression of CKD, but on the other hand excessive doses of diuretics may also decrease renal perfusion and consequently also reduce GFR. The combination of loop diuretics and thiazide diuretics has a synergistic effect that may cause excessive volume depletion and electrolyte disturbances, therefore it should be used with caution in the CRS patient.

Pimobendan improves the systolic function, which may increase GFR. Pimobendan does not enhance or suppress furosemide-induced RAAS activation.

Digoxin and other drugs with a predominant renal excretion may require closer monitoring and potential reduction of the dose.

Omega-3 fatty acids are a recommended oral supplement that has been used as an antioxidant and appetite stimulant in patients with heart and kidney disease.

Conclusions and Future Directions

An accurate appreciation of the kidney and the cardiovascular system and their interactions may have practical clinical implications. A multidisciplinary evaluation including the expertise of cardiologists and nephrologists may be the most appropriate approach for the cardiorenal patient. The outcome of CRS patients is likely to improve with the increasing awareness and ability to identify and understand the pathophysiological characteristics of cardiorenal syndrome.

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