EDITOR’S CORNER
Alfred A. Bove, MD, PhD
Editor-in-Chief, CardioSource WorldNews
Heart and Kidney:
An Inseparable Relationship
W
e 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
ACC.org/CSWN
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.
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