Cardiorenal Syndrome Overview

As the name suggests, "cardio," meaning heart, and "renal," meaning 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 cardiorenal syndrome (CRS) 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. Kidney disease, both acute, including short-duration or sudden-onset, and chronic, including long-standing or slow-onset, could also cause problems with the heart's function. 

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, the cardiorenal syndrome divides into multiple subgroups, including acute CRS, chronic CRS, acute renocardiac syndrome, chronic renocardiac syndrome, and secondary CRS. However, the details of which are beyond the scope of this article, but we will try to give an overview of the bare essentials that the average person might need to know about patients suffering from cardiorenal syndrome.

The Implications 

We live in an era of ever-ubiquitous cardiovascular disease. Over 800,000 Americans experience a heart attack every year, and over 650,000 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% 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. Studies show that patients admitted for treatment of congestive heart failure could experience worsening of kidney function to varying extents, and could possibly get diagnosed with cardiorenal syndrome.

Risk Factors

Not everyone who develops heart or kidney disease will set off a problem with the other organ causing the cardiorenal syndrome. Aside from the pre-existing history of heart failure or kidney disease, a 2020 medical study showed the most common risk factor for CRS was hypertension in 47.92% of the patients, followed closely by coronary artery disease and anemia.

How It Develops

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.

While this is not a comprehensive list, a typical cascade which sets off cardiorenal syndrome evolves from the following reasons:

1. For multiple reasons, including coronary heart disease, a patient could develop a reduction in the heart's ability to pump adequate blood, an entity which is called congestive heart failure.
2. Reduction in the cardiac output leads to decreased filling of blood in blood vessels, which causes decreased effective arterial blood volume.
3. As step two worsens, the body tries to compensate. One of the first things that goes into overdrive is the nervous system, specifically the sympathetic nervous system. 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 compensate by increasing the activity of 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. The pituitary gland begins to pump out 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. The above steps do not necessarily progress in a linear fashion, but rather in parallel.

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 causing cardiomegaly.

In principle, when the heart muscle is stretched, cardiac output should increase, but 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.

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

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

• Reduces kidney blood supply
• Increased pressure inside the kidney veins due to excess fluid
• Pressure inside the abdomen rises causing intra-abdominal hypertension.

All these maladaptive changes come together to essentially reduce the kidneys' blood supply, leading to a decline in function. This is just one of the ways cardiorenal syndrome can develop. The initial trigger can be the kidneys causing excess fluid to build up in the body, causing severe heart problems. 

Diagnosis

Clinical suspicion will often lead to a presumptive diagnosis. For example, one study suggests the following tests can help detect cardiorenal syndrome, including fluid assessments in the kidney and heart, echocardiogram to see abnormal myocardial kinetics, and an ultrasound of the kidneys to reveal dimensions.

Treatment

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.

Diuretics

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 flush out excess body fluid, are the first line of therapy.

You might have heard of the so-called "water pills," called loop diuretics. 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.

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, causing worse kidney function. This could happen from a drop in blood flow to the kidney. Hence, diuretic dosing needs to strike the right balance between leaving the patient "too dry" vs "too wet."

Fluid Removal

The efficacy of a loop diuretic depends on the kidneys' function and its ability remove excess fluid. The kidney can often become the weak link in the chain regardless of the diuretic strength. In this situation, invasive therapies to get fluid out like aquapheresis or even dialysis might be needed. These invasive therapies are controversial and evidence so far has yielded conflicting results.

Other Medications

There are other medications that are often tried (although again not necessarily standard first line treatment) and these include inotropes (which increase the heart's pumping force), renin-angiotensin blockers, and other drugs like tolvaptan.