Elsevier

Progress in Cardiovascular Diseases

Volume 54, Issue 2, September–October 2011, Pages 144-153
Progress in Cardiovascular Diseases

The Cardiorenal Syndrome in Heart Failure

https://doi.org/10.1016/j.pcad.2011.01.003Get rights and content

Abstract

The frequently occurring condition of renal failure in heart failure (HF) has been termed the cardiorenal syndrome. However, the importance of renal insufficiency in HF has only been embraced in the last decade, and therefore, the pathophysiology of cardiorenal failure is still poorly understood. The main driving force of renal failure in HF is probably hemodynamic derangement, with both reduced renal perfusion and increased venous pressure as the most important driving forces. Different cardiorenal connectors may modulate this relationship. Furthermore, renal failure is not only limited to reduced filtration but also includes glomerular hypertension and tubulointerstitial hypoxia, leading to loss of glomerular integrity and tubular damage. Recognition of these key pathophysiologic pathways in the concept of the cardiorenal syndrome is needed to value the interrelationship and incremental contribution of different risk markers and possible new treatments to improve renal function and outcome in this complex and bidirectional interplay between the heart and the kidney.

Section snippets

Hemodynamics: decreased renal perfusion

The most important pathophysiologic drive of HF is a reduction in cardiac output. This can be the consequence of decreased systolic function, impaired diastolic function, or a combination of both.11 The net result is the same: decreased cardiac output resulting in decreased organ perfusion.12

Hemodynamics: increased central venous pressure

The key disorder in HF, a reduction in cardiac output, will initiate several counterregulatory mechanisms to ensure adequate tissue perfusion. One of these mechanisms is extreme sodium and water retention by the kidney to improve effective circulating volume and, subsequently, cardiac output.27 However, in HF, this counterregulatory mechanism further increases left ventricular preload, eventually leading to a vicious circle of decreased organ perfusion and, eventually, increased venous pressure

Cardiorenal connectors

Both reduced renal perfusion and increased renal venous pressure represent the hemodynamic interaction of reduced GFR in the cardiorenal syndrome in HF. Bongartz et al27 emphasized that this model (based on Guyton) is a strong framework for the relationship between heart and kidney failure. However, although this framework works well for patient groups, it lacks accuracy in individual patients. For example, although the correlation between RBF and GFR was extremely high, the variation in GFR

Urinary albumin excretion rate

In physiologic situations, small amounts of albumin pass through the glomerular membrane, but only a very little fraction of this appears in urine.71 This is a result of an almost-complete tubular reabsorption of these small amounts of protein. However, in pathophysiologic conditions, much larger amounts ranging from micro- to macroalbuminuria appear into the urine. Albuminuria has only recently been thoroughly investigated in (chronic) HF.8, 72 In substudies of the Gruppo Italiano Per Lo

Tubular damage

In analogy to renal disease, in which both reduced GFR and albuminuria are part of the pathology of the disease, tubulointerstitial damage may develop in the cardiorenal syndrome as well. Different mechanisms may be responsible for the development of tubulointerstitial or tubular damage, but the most important ones are probably decreased local renal perfusion, increased venous congestion, and a high albumin load to the tubules.6, 26, 52, 81 Decreased renal perfusion because of decreased cardiac

Worsening renal function and acute kidney injury

Tubular markers not only indicate tubular damage but also most of these markers have been studied as very early and sensitive markers for the detection of acute kidney injury (AKI).91 In renal disease, the early detection of AKI is an important problem, as the increase in serum creatinine that accompanies AKI may lag by more than 24 hours.83 All 3 mentioned tubular markers have proved to be sensitive early markers of AKI. For instance, NGAL levels were shown to increase 1,000-fold after AKI, a

Conclusion

The cardiorenal syndrome, an elaborate interplay of pathophysiologic processes (Fig 6) that feed a vicious circle of combined heart and kidney failure, is a prevalent entity with a very poor prognosis. From a HF perspective, the main contributing mechanisms are hemodynamically driven impaired renal perfusion and increased CVP. These pathways should therefore be the main targets for treatment. Other cardiorenal connectors may modulate this relationship and can therefore serve as surrogate

Statement of Conflict of Interest

All authors declare that there are no conflicts of interest.

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    Statement of Conflict of Interest: see page 151.

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