Everything You Need to Know About Cardiorenal Syndrome

This entity could knock out two vital organs simultaneously

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As the name suggests, "cardio" (pertaining to the heart), and "renal" (pertaining to the kidneys) is a specific clinical entity where a decline in the heart's function leads to a decline in kidney function (or vice versa). Hence, the name of the syndrome actually reflects a harmful interaction between these two vital organs.

To further elaborate; the interaction is two-way. Hence, it's not just the heart whose decline could drag the kidneys down with it.

In fact, kidney disease, both acute (short duration, sudden onset) or chronic (long-standing, slow onset chronic disease) could also cause problems with the heart's function. Finally, an independent secondary entity (like diabetes) could hurt both the kidneys and the heart, leading to a problem with both organ's functioning.

Cardiorenal syndrome may start off in acute scenarios where a sudden worsening of the heart (for instance, a heart attack which leads to acute congestive heart failure) hurts the kidneys. However, that might not always be the case since long-standing chronic congestive heart failure (CHF) can also lead to a slow yet progressive decline in kidney function. Similarly, patients with chronic kidney disease (CKD) are at higher risk for heart disease.

Based on how this interaction is initiated and develops, cardiorenal syndrome is divided into multiple subgroups, the details of which are beyond the scope of this article.

However, I will try to give an overview of the bare essentials that the average person might need to know about patients suffering from cardiorenal syndrome.

Why Must You Know About Cardiorenal Syndrome: the Implications 

We live in an era of ever ubiquitous cardiovascular disease. Over 700,000 Americans experience a heart attack every year, and over 600,000 people die of heart disease annually.

One of the complications of this is congestive heart failure. When failure of one organ complicates the function of the second, it significantly worsens the patient's prognosis. For instance, an increase in serum creatinine level by just 0.5 mg/dL is associated with as much as a 15 percent increase risk of death (in the setting of cardiorenal syndrome).

Given these implications, cardiorenal syndrome is an area of vigorous research. It is not an uncommon entity by any means. By day three of hospitalization, up to 60 percent of patients (admitted for treatment of congestive heart failure) could experience worsening of kidney function to varying extents, and will get diagnosed with cardiorenal syndrome. 

What Are the Risk Factors?

Obviously, not everyone who develops heart or kidney disease will set off a problem with the other organ. However, certain patients might be higher risk than others. Patients with the following are considered high risk:

  • Pre-existing history of heart failure or kidney disease 

How Does Cardiorenal Syndrome Develop?​

Cardiorenal syndrome begins with our body's attempt to maintain adequate circulation. While these attempts might be beneficial in the short-term, over the long-term, these very changes become maladaptive and lead to worsening of organ function.

A typical cascade which sets off cardiorenal syndrome could begin and evolve along the following steps:

  1. For multiple reasons (coronary heart disease being one common cause), a patient could develop a reduction in the heart's ability to pump adequate blood, an entity which we call congestive heart failure or CHF.
  2. Reduction in the heart's output (also called "cardiac output") leads to decreased filling of blood in blood vessels (arteries). We physicians call this "decreased effective arterial blood volume". 
  3. As step two worsens, our body tries to compensate. Mechanisms that we have all developed as part of evolution kick in. One of the first thing that goes into an overdrive is the nervous system, specifically something called the "sympathetic nervous system" (SNS). This is a part of the same system associated with the so-called flight or fight response.  Increased activity of the sympathetic nervous system will constrict the arteries in an attempt to raise blood pressure and maintain organ perfusion.
  4. The kidneys chip in by increasing the activity of something called the "renin-angiotensin-aldosterone system" (RAAS) .  The goal of this system is also to increase the pressure and volume of blood in the arterial circulation. It does so by multiple sub-mechanisms (including supporting the above-mentioned sympathetic nervous system), as well as water and salt retention in the kidneys.
  5. Our pituitary gland begins to pump out ADH (or the anti-diuretic hormone), again leading to water retention from the kidneys.  

The detailed physiology of each specific mechanism is beyond the scope of this article. I should emphasize that the above steps do not necessarily progress in a linear fashion, but rather in parallel. And finally, this is not a comprehensive list.

The net result of the above compensatory mechanisms is that more and more salt and water start to get retained in the body, making the total volume of body fluid go up. This, among other things, will increase the heart's size over a period of time (a change called "cardiomegaly"). In principle, when the heart muscle is stretched, cardiac output should increase.  This however only works within a certain range. Beyond that, the heart's output will not increase in spite of increased stretch/size which follows the incessant gain in blood volume. This phenomenon is elegantly illustrated in medical textbooks as something called the "Frank-Starling curve".

Hence, the patient is typically left with an enlarged heart, a reduced cardiac output, and too much fluid in the body (the cardinal features of CHF). Fluid overload will lead to symptoms including shortness of breath, swelling or edema, etc.

So how is all this harmful to the kidneys? Well, the above mechanisms also do the following:

All these maladaptive changes come together to essentially reduce the kidneys' blood supply (perfusion) leading to a worsened kidney function. This wordy explanation will hopefully give you an idea of how a failing heart drags down the kidneys with it.

This is just one of the ways cardiorenal syndrome can develop. The initial trigger can easily be the kidneys instead, where malfunctioning kidneys (advanced chronic kidney disease, for instance) cause excess fluid to build up in the body (not unusual in patients with kidney disease). This excess fluid can overload the heart and cause it to progressively fail.

How Is Cardiorenal Syndrome Diagnosed?

Clinical suspicion by the astute physician will often lead to a presumptive diagnosis. However, typical tests to check kidney and heart function will be helpful, although not necessarily nonspecific. These tests are:

  • For the kidneys: Blood tests for creatinine/GFR and urine tests for blood, protein, etc. The sodium level in the urine might be helpful (but needs to be interpreted carefully in patients on diuretics). Imaging tests like ultrasound are often done as well.
  • For the heart: Blood tests for troponin, BNP, etc. Other investigations like EKG, echocardiogram, etc.

The typical patient would have a history of heart disease with recent worsening (CHF), accompanied by the above signs of worsening kidney function. 

Treatment of Cardiorenal Syndrome 

As mentioned above, management of cardiorenal syndrome is an active area of research for obvious reasons. Patients with cardiorenal syndrome experience frequent hospitalizations and increased morbidity as well as high risk of death.  Therefore, effective treatment is essential. Here are some options:

  1. Since the cascade of cardiorenal syndrome is typically set off by a failing heart leading to an excess volume of fluid, diuretic medications (designed to get rid of excess fluid from the body) are the first line of therapy. You might have heard of the so-called "water pills" (specifically called "loop diuretics", a common example is furosemide, or Lasix).  If the patient is sick enough to require hospitalization, injections of intravenous loop diuretics are used. If bolus injections of these medications don't work, a continuous drip may be required.
  2. However, treatment is not that straightforward. The very prescription of a loop diuretic can sometimes cause the clinician to "overshoot the runway" with fluid removal, and cause the serum creatinine level to go up (which translates into a worse kidney function). This could happen from a drop in kidneys blood perfusion. Hence, diuretic dosing needs to strike the right balance between leaving the patient "too dry" vs "too wet."
  3. Finally, remember that the efficacy of a loop diuretic depends on the kidneys' function and its ability to get excess fluid out. Hence, the kidney can often become the weak link in the chain. That is, regardless of how strong a diuretic, if the kidneys are not working well enough, no fluid might be removed from the body in spite of aggressive efforts.  
  4. In the above situation, invasive therapies to get fluid out like aqua pheresis or even dialysis might be needed. These invasive therapies are controversial and evidence so far has yielded conflicting results. Hence, by no means are they the first line of therapy of this condition.
  5. There are other medications that are often tried (although again not necessarily standard first line treatment) and these include the so-called inotropes (which increase the heart's pumping force), renin-angiotensin blockers, as well as experimental drugs to treat cardiorenal syndrome like tolvaptan.

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