Acute cardiorenal syndrome: Mechanisms and clinical implications

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Venovenous ultrafiltration (or aquapheresis) employs an extracorporeal circuit, similar to the one used in hemodialysis, which removes iso-osmolar fluid at a fixed rate.34 Newer ultrafiltration systems are more portable, can be used with peripheral venous access, and require minimal nursing supervision.35

Although ultrafiltration seems an attractive alternative to diuresis in acute heart failure, studies have been inconclusive. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial compared ultrafiltration and diuresis in 188 patients with acute heart failure and acute cardiorenal syndrome.36 Diuresis, performed according to an algorithm, was found to be superior to ultrafiltration in terms of a bivariate end point of change in weight and change in serum creatinine level at 96 hours. However, the level of cystatin C is thought to be a more accurate indicator of renal function, and the change in cystatin C level from baseline did not differ between the two treatment groups. Also, the ultrafiltration rate was 200 mL per hour, which, some argue, may have been excessive and may have caused intravascular depletion.

Although the ideal rate of fluid removal is unknown, it should be individualized and adjusted based on the patient’s renal function, volume status, and hemodynamic status. The initial rate should be based on the degree of fluid overload and the anticipated plasma refill rate from the interstitial fluid.37 For example, a malnourished patient may have low serum oncotic pressure and hence have low plasma refill upon ultrafiltration. Disturbance of this delicate balance between the rates of ultrafiltration and plasma refill may lead to intravascular volume contraction.

In summary, although ultrafiltration is a valuable alternative to diuretics in resistant cases, its use as a primary decongestive therapy cannot be endorsed in view of the current data.


Inotropes such as dobutamine and milrinone are typically used in cases of cardiogenic shock to maintain organ perfusion. There is a physiologic rationale to using inotropes in acute cardiorenal syndrome as well, especially when the aforementioned strategies fail to overcome diuretic resistance.7

Inotropes increase cardiac output, improve renal blood flow, improve right ventricular output, and thereby relieve systemic congestion. These hemodynamic effects may improve renal perfusion and response to diuretics. However, clinical evidence to support this is lacking.

The Renal Optimization Strategies Evaluation (ROSE) trial enrolled 360 patients with acute heart failure and renal dysfunction. Adding dopamine in a low dose (2 μg/kg/min) to diuretic therapy had no significant effect on 72-hour cumulative urine output or renal function as measured by cystatin C levels.38 However, acute kidney injury was not identified in this trial, and the renal function of many of these patients may have been at its baseline when they were admitted. In other words, this trial did not necessarily include patients with acute kidney injury along with acute heart failure. Hence, it did not necessarily include patients with acute cardiorenal syndrome.

Figure 2.

Figure 2.

Nonetheless, inotropic support and temporary mechanical circulatory support should be reserved as a last resort. A stepped approach to management is summarized in Figure 2.


Vasodilators such as nitroglycerin, sodium nitroprusside, and hydralazine are commonly used in patients with acute heart failure, although the clinical evidence supporting their use is weak.

Physiologically, arterial dilation reduces afterload and can help relieve pulmonary congestion, and venodilation increases capacitance and reduces preload. In theory, venodilators such as nitroglycerin can relieve renal venous congestion in patients with acute cardiorenal syndrome, thereby improving renal perfusion.

However, the use of vasodilators is often limited by their adverse effects, the most important being hypotension. This is especially relevant in light of recent data identifying reduction in blood pressure during treatment of acute heart failure as an independent risk factor for worsening renal function.39,40 It is important to note that in these studies, changes in cardiac index did not affect the propensity for developing worsening renal function. The precise mechanism of this finding is unclear but it is plausible that systemic vasodilation redistributes the cardiac output to nonrenal tissues, thereby overriding the renal autoregulatory mechanisms that are normally employed in low output states.

Preventive strategies

Various strategies can be used to prevent acute cardiorenal syndrome. An optimal outpatient diuretic regimen to avoid hypervolemia is essential. Patients with advanced congestive heart failure should be followed up closely in dedicated heart failure clinics until their diuretic regimen is optimized. Patients should be advised to check their weight on a regular basis and seek medical advice if they notice an increase in their weight or a reduction in their urine output.


  • A robust clinical definition of cardiorenal syndrome is lacking. Hence, recognition of this condition can be challenging.
  • Volume overload is central to its pathogenesis, and accurate assessment of volume status is critical.
  • Renal venous congestion is the major mechanism of type 1 cardiorenal syndrome.
  • Misdiagnosis can have devastating consequences, as it may lead to an opposite therapeutic approach.
  • Fluid removal by various strategies is the mainstay of treatment.
  • Temporary inotropic support should be saved for the last resort.

Next Article:

Hemodynamically, the kidney is at the heart of cardiorenal syndrome

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