Heart and Kidney
An Inseparable Relationship
Editor's Corner | Alfred A. Bove, MD, PhD
We have known for many years that the kidney is more than a filtration organ tasked with removing waste and maintaining volume homeostasis. As we learned in physiology class, the kidney incorporates intrinsic regulatory systems to maintain a constant blood flow to allow appropriate filtering of plasma for excretion of urea and maintenance of fluid volume and sodium balance.
This month’s cover story reviews the latest information on how the cross-talk between the heart and kidneys should be taken into account when we’re considering pharmacologic or interventional therapy. All of this goes back to our early understanding of renal blood flow, which can be attributed to the physiologist Homer Smith, MD. He developed the clearance method of measuring glomerular blood flow and described the blood flow control that the kidney exerts to maintain a constant filtration pressure. We also learned that the kidney boasts important blood pressure regulatory functions. This again is a system built into the kidney to preserve blood flow, so if the renal blood flow drops, release of renin increases blood pressure to restore blood flow to normal.
Angiotensin also stimulates release of aldosterone that results in sodium and fluid retention to expand blood volume. The renin-angiotensin-aldosterone system (RAAS) has become an important component of hypertension management where inhibition of angiotensin activation by an angiotensin-converting enzyme inhibitor has become a mainstay of hypertension management. Blocking the angiotensin receptor site with a receptor blocker also stands as an important component of hypertension management. Additionally, we now understand that the kidney controls sympathetic activation, and ablation of the sympathetic nerves to the kidney can significantly affect blood pressure. The reduction in sympathetic nervous system (SNS) activity also seems to have a positive effect on atrial and ventricular arrhythmias.
We must pay close attention to the RAAS and SNS in heart failure (HF). When cardiac output is reduced due to impaired left ventricular function, the kidneys again release renin in an attempt to increase blood pressure and preserve renal blood flow. Overactivity of the RAAS becomes detrimental to the heart, both by maintaining a high afterload and stimulating sodium and water retention, and by direct toxic effects of angiotensin on the myocardium. So the efforts of the kidney to preserve renal blood flow and filtration actually become detrimental in HF, and RAAS inhibition is an important goal of therapy.
SNS stimulation in HF similarly results in toxic effects on the myocardium. It is apparent that many of our therapies for cardiac disorders are targeted to the kidneys. The heart also has regulatory effects on the kidney. The most relevant is the release of natriuretic peptides from cardiac tissue when the atria are stretched from excess blood volume. The natriuretic peptides stimulate the kidney to excrete more water and attempt to restore blood volume to normal. The atria can be stretched by shifts of blood from the venous system into the central circulation. For example, this occurs with water immersion, causing the well-known phenomenon called swimmer’s diuresis.
All of these regulatory systems are focused on maintaining normal blood volume, normal blood pressure, and normal tissue perfusion. Heart failure is the best example of these bidirectional regulatory systems gone awry. Therapy of HF is based on inhibiting the RAAS and the SNS, and more recently, by augmenting the neuropeptide system that counters effects of the RAAS and the SNS. The emergence of drugs that increase activity of neuropeptides promises to add an important third leg to HF therapy.
Cardiac effects on renal function often involve reduction in renal blood flow, venous congestion, and kidney injury related to acute HF. In addition to the hemodynamic problem, inflammatory mediators resulting from acute heart failure also produce kidney injury. At the same time, aldosterone and angiotensin can promote myocardial fibrosis by activating galactin III and other inflammatory mediators. Chronic renal insufficiency can ultimately result in a uremic cardiomyopathy.
More current studies indicate yet another level of interaction between the heart and kidneys. A recent article in JACC discusses inflammatory mediators activated by acute HF and acute kidney injury that can cause both kidney and cardiac injury.1 Chronic kidney disease (CKD) stimulates release of a fibroblast growth factor, FGF-23, that causes myocardial hypertrophy. This link helps explain the presence of hypertrophy in many patients with CKD, and is particularly active in hemodialysis patients. Studies using blockers of FGF-23 release suggest that cardiovascular events are reduced when FGF-23 levels are reduced.
The interactions between heart and kidney are numerous. Many start as normal physiologic interactions that aim toward circulatory homeostasis. When either acute HF or acute kidney injury occur, mediators from either organ result in injury to the other. Moreover, kidney disease seems to accelerate heart disease well before it has ravaged the kidneys. Our therapies for cardiac failure often involve treatment of the kidney, and therapy of renal insufficiency often involves managing cardiac disorders. It is essential that we consider treating both organs when either is failing. New understanding of these complex heart-kidney interactions is providing not only insights but new medications to reduce or eliminate the toxic interaction between these two essential organs.
- Husain-Syed F, McCullough PA, Birk H, et al.
- J Am Coll Cardiol. 2015;65:2433-48.
< Back to Listings