Acute cardiorenal syndrome: Mechanisms and clinical implications

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Cardiac and renal dysfunction often coexist, and one begets the other. The association is referred to as cardiorenal syndrome. One subtype, acute cardiorenal syndrome, is often described as a clinical scenario in which acute worsening of cardiac function leads to acute kidney injury. Though this definition covers the basic pathophysiologic framework, a robust clinical definition is still lacking. Acute cardiorenal syndrome is common and often leads to emergency room visits and hospitalization. Our understanding of the hemodynamic mechanisms of acute cardiorenal syndrome is advancing. Correction of hypervolemia is the mainstay of therapy.


  • Acute cardiorenal syndrome is the acute worsening of renal function due to acute decompensated heart failure.
  • The most important mechanism of acute cardiorenal syndrome is now believed to be systemic congestion leading to increased renal venous pressure, which in turn reduces renal perfusion.
  • The major alternative in the differential diagnosis of acute cardiorenal syndrome is renal injury due to hypovolemia. Differentiating the 2 may be challenging if signs of systemic and pulmonary congestion are not obvious.
  • Diuretic resistance is common in acute cardiorenal syndrome but may be overcome by using higher doses of diuretics and combinations of diuretics that block reabsorption at different segments of the renal tubules.



As the heart goes, so go the kidneys—and vice versa. Cardiac and renal function are intricately interdependent, and failure of either organ causes injury to the other in a vicious circle of worsening function.1

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Here, we discuss acute cardiorenal syndrome, ie, acute exacerbation of heart failure leading to acute kidney injury, a common cause of hospitalization and admission to the intensive care unit. We examine its clinical definition, pathophysiology, hemodynamic derangements, clues that help in diagnosing it, and its treatment.


The Acute Dialysis Quality Initiative classification of cardiorenal syndromes
Cardiorenal syndromes are a group of linked disorders of the heart and kidneys. They are classified (Table 1) according to whether the problem is acute or chronic and whether the primary problem is in the heart (cardiorenal syndrome), the kidneys (renocardiac syndrome), or another organ (secondary cardiorenal syndrome).2 This classification is still evolving.

Two types of acute cardiac dysfunction

Although these definitions offer a good general description, further clarification of the nature of organ dysfunction is needed. Acute renal dysfunction can be unambiguously defined using the AKIN (Acute Kidney Injury Network) and RIFLE (risk, injury, failure, loss of kidney function, and end-stage kidney disease) classifications.3 Acute cardiac dysfunction, on the other hand, is an ambiguous term that encompasses 2 clinically and pathophysiologically distinct conditions: cardiogenic shock and acute heart failure.

Cardiogenic shock is characterized by a catastrophic compromise of cardiac pump function leading to global hypoperfusion severe enough to cause systemic organ damage.4 The cardiac index at which organs start to fail varies in different cases, but a value of less than 1.8 L/min/m2 is typically used to define cardiogenic shock.4

Acute heart failure, on the other hand, is defined as gradually or rapidly worsening signs and symptoms of congestive heart failure due to worsening pulmonary or systemic congestion.5 Hypervolemia is the hallmark of acute heart failure, whereas patients with cardiogenic shock may be hypervolemic, normovolemic, or hypovolemic. Although cardiac output may be mildly reduced in some cases of acute heart failure, systemic perfusion is enough to maintain organ function.

These two conditions cause renal injury by distinct mechanisms and have entirely different therapeutic implications. As we discuss later, reduced renal perfusion due to renal venous congestion is now believed to be the major hemodynamic mechanism of renal injury in acute heart failure. On the other hand, in cardiogenic shock, renal perfusion is reduced due to a critical decline of cardiac pump function.

The ideal definition of acute cardiorenal syndrome should describe a distinct pathophysiology of the syndrome and offer distinct therapeutic options that counteract it. Hence, we propose that renal injury from cardiogenic shock should not be included in its definition, an approach that has been adopted in some of the recent reviews as well.6 Our discussion of acute cardiorenal syndrome is restricted to renal injury caused by acute heart failure.


Multiple mechanisms have been implicated in the pathophysiology of cardiorenal syndrome.7,8

Sympathetic hyperactivity is a compensatory mechanism in heart failure and may be aggravated if cardiac output is further reduced. Its effects include constriction of afferent and efferent arterioles, causing reduced renal perfusion and increased tubular sodium and water reabsorption.7

The renin-angiotensin-aldosterone system is activated in patients with stable congestive heart failure and may be further stimulated in a state of reduced renal perfusion, which is a hallmark of acute cardiorenal syndrome. Its activation can cause further salt and water retention.

However, direct hemodynamic mechanisms likely play the most important role and have obvious diagnostic and therapeutic implications.

Elevated venous pressure, not reduced cardiac output, drives kidney injury

The classic view was that renal dysfunction in acute heart failure is caused by reduced renal blood flow due to failing cardiac pump function. Cardiac output may be reduced in acute heart failure for various reasons, such as atrial fibrillation, myocardial infarction, or other processes, but reduced cardiac output has a minimal role, if any, in the pathogenesis of renal injury in acute heart failure.

As evidence of this, acute heart failure is not always associated with reduced cardiac output.5 Even if the cardiac index (cardiac output divided by body surface area) is mildly reduced, renal blood flow is largely unaffected, thanks to effective renal autoregulatory mechanisms. Not until the mean arterial pressure falls below 70 mm Hg do these mechanisms fail and renal blood flow starts to drop.9 Hence, unless cardiac performance is compromised enough to cause cardiogenic shock, renal blood flow usually does not change significantly with mild reduction in cardiac output.

Hanberg et al10 performed a post hoc analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheter Effectiveness (ESCAPE) trial, in which 525 patients with advanced heart failure underwent pulmonary artery catheterization to measure their cardiac index. The authors found no association between the cardiac index and renal function in these patients.


Next Article:

Hemodynamically, the kidney is at the heart of cardiorenal syndrome

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