TABLE
Cardiorenal Syndrome (CRS): A pathophysiologic
disorder of the heart and kidneys whereby acute
or chronic dysfunction in one organ may induce
acute or chronic dysfunction in the other organ
CRS Type 1 (Acute Cardiorenal Syndrome):
Abrupt worsening of cardiac function (e.g., acute
cardiogenic shock or acutely decompensated
heart failure [HF]) leading to acute kidney injury
(AKI)
CRS Type 2 (Chronic Cardiorenal Syndrome):
Chronic abnormalities in cardiac function (e.g.,
chronic HF) causing progressive chronic kidney
disease (CKD)
CRS Type 3 (Acute Renocardiac Syndrome):
Abrupt worsening of renal function (e.g., acute
kidney ischemia or glomerulonephritis) causing
acute cardiac disorder (e.g., HF, arrhythmia, pulmonary edema)
CRS Type 4 (Chronic Renocardiac Syndrome):
CKD (e.g., chronic glomerular or interstitial disease) contributing to decreased cardiac function,
cardiac hypertrophy, or increased risk of adverse
cardiovascular events
CRS Type 5 (Secondary Cardiorenal Syndrome):
Systemic condition (e.g., diabetes, sepsis) causing
both cardiac and renal dysfunction
Adapted from Ronco C, et al. J Am Coll Cardiol.
2008;52:1527-39.
ologic disorders of the heart or kidneys where acute
or chronic dysfunction of one organ induces acute
or chronic dysfunction in the other. (See TABLE.)
The term is most commonly applied to patients with
HF (as in Cardiorenal Syndrome Types 1 and 2), but
technically covers heart-kidney involvement in many
other conditions, such as sepsis, diabetes, and AKI.
In type 3 acute renocardiac syndrome, for
example, the kidneys stand as the lead organ, as
Peter A. McCullough, MD, MPH, explained in
an interview with CSWN. Dr. McCullough, from
the Baylor Heart and Vascular Institute in Dallas,
Texas, is a recognized authority on the role of CKD
as a cardiovascular risk state with more than 1,000
publications, including the “Interface between Renal
Diseases and Cardiovascular Illness” in the seminal
text Braunwald’s Heart Disease, 10th Edition. He is the
current Chair of the National Kidney Foundation’s
Kidney Early Evaluation Program, the nation’s largest
community screening effort for chronic diseases.
“Type 3 is acute kidney injury that leads to cardiac decompensation and will be seen mostly in the
hospital setting with serious forms of acute kidney
injury, where primary volume overload and neurohormonal signaling lead to cardiac decompensation,”
said Dr. McCullough. “We see this fairly rarely in
patients with crush injury, but you’ll hear about
individuals who have severe trauma, for example,
and go into kidney failure because of the volume
overload, and then even a healthy heart can go into
heart failure.”
Type 4 CRS describes CKD, leading primarily
to HF, but possibly to acute coronary syndromes,
stroke, or arrhythmias, too. Finally, CRS type 5
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describes a systemic insult to both the heart and
the kidneys, such as sepsis, where both organs are
injured simultaneously in persons with previously
normal heart and kidney function.
And Lung Makes 3
A June JACC State-of-the-Art review by Faeq HusainSyed, MD, and colleagues explained the complex
interactions between the heart, lungs, and kidneys,
their perpetuating nature, and the “cycles of increased susceptibility and reciprocal progression.”5
Dr. Husain-Syed is also from the IRRIV in Vicenza.
Dr. McCullough, a second author on the review,
observed that the lungs are caught right in the
crossfire in this cycle of multi-organ crosstalk. They
are also highly immunologic, representing a gateway
to the environment, and have important pathophysiological connections to the failing heart and kidneys.
However, he added, the lungs play more the part of
a “victim” than a “participant” in the organ injury
syndrome.
“The heart and kidneys are signaling each other
back and forth fiercely in both health and disease;
there are probably 8 to 12 known neurohormonal
self-signaling systems where the heart and kidneys
are communicating,” said Dr. McCullough. “The
lungs are less active in terms of signaling, but they
certainly bear the consequences of excessive volume
overload, and capillary and then pulmonary edema.”
Multiple dependent inflammatory pathways promote injury and elevate the risk for chronic disease
of the heart, lung, and kidney, including increased
expression of soluble pro-inflammatory mediators,
innate and adaptive immunity, physiological derange-
FIGURE 1. Cellular and Molecular Crosstalk and
Potential Biomarkers in Acute and Chronic
Cardio-pulmonary-renal Interactions
ments, and cellular apoptosis. (See FIGURE 1.)
Dr. McCullough doesn’t think the term cardiopulmonary renal interactions (CPRI) is going to replace
the better-known “cardiorenal syndromes,” but
rather the goal of the review was more to serve as a
reminder that the lungs function as more than a silent partner in cardiorenal syndromes and shouldn’t
be forgotten.
“We are working on finding active prevention
and treatment approaches for the heart and kidneys:
cellular protectants, drugs that influence a whole
variety of cellular processes, drugs that interfere
with adverse cell signaling -- and we’re hoping for a
breakthrough, which, I think when we find one, is
going to have a major impact worldwide.”
“Evidence-free Zone”
“Although the heart has intense relationships with
other organs, the marriage to the kidneys is particularly speci