What are the definitions and causes of Cardiorenal Syndrome (CRS), a condition characterized by impaired renal (kidney) function and cardiovascular disease?

From the Guidelines

Cardiorenal syndrome (CRS) is a disorder where acute or chronic dysfunction in one organ induces acute or chronic dysfunction in the other, and it is classified into five types, with the primary causes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction. The classification of CRS includes Type 1 (acute heart failure causing acute kidney injury), Type 2 (chronic heart failure leading to progressive kidney disease), Type 3 (acute kidney injury causing acute cardiac dysfunction), Type 4 (chronic kidney disease contributing to heart failure), and Type 5 (systemic conditions affecting both organs simultaneously) 1. The primary causes of CRS include:

• Hemodynamic changes: reduced cardiac output decreasing renal perfusion, while venous congestion increases renal back-pressure
• Neurohormonal activation: the renin-angiotensin-aldosterone system becomes overactivated, leading to fluid retention, vasoconstriction, and fibrosis in both organs
• Inflammation and oxidative stress: damage both cardiac and renal tissues Management of CRS requires addressing the underlying cause while optimizing fluid status, using diuretics judiciously, considering SGLT2 inhibitors, and potentially using ACE inhibitors or ARBs at appropriate doses based on blood pressure and renal function 1. Early recognition of this bidirectional relationship is crucial for preventing the progressive worsening that occurs when dysfunction in one organ accelerates deterioration in the other. It is also important to note that cardiovascular disease is a major complication of chronic kidney disease, and patients with chronic kidney disease should be considered at high risk for subsequent cardiovascular events 1. Therefore, management of CRS should also involve measures to prevent and treat cardiovascular disease, such as controlling blood pressure, lipid levels, and glucose levels, and using medications that have been shown to reduce cardiovascular risk in patients with chronic kidney disease.

From the Research

Definitions of Cardiorenal Syndrome

• Cardiorenal syndrome (CRS) is a clinical entity characterized by the interdependence of the cardiovascular and renal systems, where primary disorders of either system can disturb the other system 2.
• It is defined as a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ 2, 3.
• CRS encompasses a spectrum of disorders involving both the heart and kidneys, representing the confluence of heart-kidney interactions across several interfaces 3.

Classification of Cardiorenal Syndrome

• The ADQI organization has proposed a classification of CRS into five subtypes:
  • CRS type 1: acute worsening of heart function leading to kidney injury and/or dysfunction
  • CRS type 2: chronic abnormalities in heart function leading to kidney injury or dysfunction
  • CRS type 3: acute worsening of kidney function leading to heart injury and/or dysfunction
  • CRS type 4: chronic kidney disease leading to heart injury, disease and/or dysfunction
  • CRS type 5: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney 2, 4

Causes of Cardiorenal Syndrome

• The pathophysiology of CRS is complicated and involves multiple body systems, including hemodynamic, neurohormonal, and inflammatory mechanisms 4.
• Risk factors for CRS include diabetes, hyperlipidemia, obesity, hypertension, and renal impairment, which can act synergistically to magnify healthcare costs 5.
• Other pathological mechanisms associated with CRS include oxidative stress, hyperactive renin-angiotensin-aldosterone system, maladaptive Wnt/β-catenin signalling pathway, and profibrotic TGF-β1/Smad signalling pathway 4.