Cardiorenal Syndrome

What is cardiorenal syndrome?

Cardiorenal syndrome (CRS) is a disorder of the kidneys and the heart. The heart supplies organs and tissues with blood, while kidneys play a role in fluid balance therefore dysfunction in one of these organs often leads to dysfunction in the other. It can be acute or chronic dysfunction of one of these organs that leads to acute or long term dysfunction of the other. Cardiorenal Syndrome is characterized by a triad of:

• Decreased kidney function
• Therapy-resistant heart failure with congestion
• Worsening of kidney function during heart failure therapy ^[1].

Types

1. Acute cardiorenal
   • Acute cardiac dysfunction that leads to acute kidney injury
   • Example: sudden heart attack leads to heart failure and renal dysfunction (read about Broken heart syndrome)
2. Chronic cardiorenal
   • Chronic heart failure leads to renal dysfunction (read about Kearns-Sayre syndrome)
3. Acute renocardiac
   • Acute kidney injury leads to acute heart dysfunction
   • Example: acute kidney failure leads to uremic cardiomyopathy
4. Chronic renocardiac
   • Chronic failure of kidneys leads to cardiac dysfunction
5. Secondary
   • Systemic condition is causing heart and kidney dysfunction
   • Example: CRS due to septic shock (also read about toxic shock syndrome) ^[2].

Causes

Causes of Cardiorenal Syndrome vary between the different types of this disease. In some occasions it is not easy to determine if the renal or cardiac condition was the first to cause the other.

• Type 1 CRS:
  • Acute decompensated heart failure
  • Acute coronary syndrome
  • Cardiogenic shock (read about Wolff-Parkinson-White syndrome)
  • Low-flow syndrome following heart surgery
• Type 2 CRS:
  • Chronic heart failure
  • Atrial fibrillation
  • Congenital cyanotic heart disease
  • Chronic ischemic heart disease
• Type 3 CRS:
  • Drug induced acute renal disease
  • Acute renal failure after major surgery
  • Acute nephritic syndromes
  • Rhabdomyolysis
• Type 4 CRS is believed to be severely influenced by the fear of using medication to modify cardiovascular risk factors because they can negatively influence kidney function.
• Type 5 CRS:
  • Sepsis
  • Systemic lupus erithematosus
  • Amyloidosis
  • Sarcoidosis^[3]

Risk factors

Risk factors of CRS include:

• Old age
• Other conditions
  • Diabetes
  • Uncontrolled hypertension
  • Anemia
  • Vascular disease
• Medications
  • Non-steroid anti-inflammatory drugs
  • Diuretics
  • ACE inhibitors
  • Aldosterone receptor antagonists
• History of heart failure
• Myocardial infarction in the past
• Elevated levels of cardiac troponin^[1]

Pathophysiology

The pathophysiology of Cardiorenal Syndrome is still unclear, but several mechanisms of the body have been found to play a role in developing this condition.

Renin-angiotensin-aldosterone

• • Heart failure leads to decreased cardiac output and blood pressure, which lowers the renal perfusion.
  • Decreased renal perfusion activates RAAS which is responsible for:
    • Constriction of blood vessels
    • Retention of sodium
    • Activation of enzyme NADPH-oxidase by angiotensin II, which leads to formation of reactive oxygen species that damage both heart and kidneys.

Endothelin

• • Release of endothelin causes constriction of blood vessels and induces heart muscle hypertrophy

Arginine vasopressin

• • Causes fluid retention and potentiation of angiotensin II and noradrenaline, which has adverse effects on CRS
  • Stimulates heart muscle hypertrophy

B-type natriuretic peptide

• • Has beneficial effects against progression of Cardiorenal Syndrome:
    • Inhibits RAAS, endothelin-1 and constriction of blood vessels
    • Promotes diuresis
    • Enhances sodium excretion
    • Increases glomerular filtration

Nitric oxide and reactive oxygen

• • Oxidative stress plays major role in inflammation response by promoting production of pro-inflammatory agents (cytokines)
  • These cytokines have negative role in atherosclerosis process, as well as negative impact on heart muscle function

Sympathetic nervous system

• • SNS is activated in heart failure by baroreflex- when blood pressure gets critically low, SNS activates to preserve cardiac output.
  • SNS can induce heart muscle cell necrosis, death and hypertrophy (also read about General adaptation syndrome)^[4]

Diagnosis

The diagnosis of Cardiorenal Syndrome is usually made based on the underlying condition. In most cases, laboratory studies show the status of the patient.

• Serum creatinine levels- can be normal or increased
  • Decreased creatinine clearance indicates worsening of CRS
• Glomerular filtration rate
  • Decreased glomerular filtration rate indicates worsening of the condition
  • Used for evaluating the patient and planning the treatment^[4]

Treatment

Cardiorenal Syndrome is a heterogeneous and complex condition which makes management difficult. Each patient has their own medical history therefore the medications must be combined and adjusted for each case. The most important indicator while managing CRS is patient’s body weight. Drug classes that are used in treating CRS are:

• Diuretics
  • Pros: Provide diuresis, excretion of natrium and short-term symptom relief
  • Cons: exacerbate neuro-hormonal activity, worsens the functional capabilities of left ventricle. Also long term use increases kidney dysfunction.
• Dopamine
  • Low doses are used together with diuretics.
  • Cons: impair oxygen supply to kidneys
• Inotropes
  • Effective if CRS is caused by low cardiac output
• Nesiritide
  • Nesiritide is an effective blood vessel dilatator that has mild effect of diuretics.
• ACE inhibitors

Other treatments

Ultrafiltration is used in cases of chronic CRS when renal function is continuously declining and when the patient has severe edema. This method provides short term effect.

Cardiac transplantation and ventricular assist devices are sometimes used. However these treatment modalities have high mortality rate.

Prognosis

The exact pathophysiology and treatment of Cardiorenal Syndrome is not yet understood therefore most of the patients have poor prognosis. CRS sets in a cycle that leads to further kidney and heart damage. Serum creatinine level increase and decrease in creatinine clearance is associated with worse prognosis. Renal failure radically worsens the prognosis for patients with heart failure, as well as heart failure worsens the prognosis for patients undergoing dialysis. Survival rate in these patients is less than 50%. Kidney transplantation for patients with renal failure can increase survival ^[4,6].

If you found this article helpful, share it on social media. For your comments and personal experience use the comments box below.

References

1. General information for patients: http://lifeinthefastlane.com/ccc/cardiorenal-syndrome/
2. Types of CRS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021842/table/tab1/
3. Causes of CRS: http://www.ijcme-journal.com/article/S2214-7624(14)00055-3/pdf
4. Diagnostics and pathogenesis of CRS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663478/
5. Treatment: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794438/
6. Prognosis: https://www.ncbi.nlm.nih.gov/pubmed/15808763