What is Cardiorenal Syndrome?
The coexistence of chronic kidney disease and heart disease is quite common. Both these diseases interact and patients with chronic kidney disease have a greater risk to develop atherosclerotic heart disease and cardiac failure, whereas 50% mortality due to renal failure is often accompanied by cardiovascular disease. This interaction is clinically termed as a cardiorenal syndrome.
According to report obtain from the National Heart, Lung, and Blood Institute in 2004, the cardiorenal syndrome can be defined as a condition in which treatment does not provide enough effective result for relieving congestive symptoms of heart failure due to the reduction of glomerulus filtration rate and subsequent declined renal functionality2.
Cardiorenal interactions hamper blood flow in both upper and lower segment of the body and that may responsible for the reduction in Gfr,though previously it has an assumption that reduction in renal blood flow causes a lower rate of Gfr. Therefore, the cardiac and kidney disorders are interrelated and acute or chronic dysfunction in one organ negatively influence other organ’s functioning.
There are five different subtypes identified in Cardiorenal Syndrome, they are as follows
- Type 1 or Acute Cardio Renal Syndrome: an acute degenerative cardiac condition leads to renal dysfunction;
- Type 2 or Chronic Cardio Renal Syndrome: chronic cardiac dysfunction leads to renal dysfunction;
- Type 3 or Acute Reno Cardiac Syndrome: an acute renal function worsening condition leads to cardiac dysfunction;
- Type 4 or Chronic Reno Cardiac Syndrome: chronic impaired renal functioning causes cardiac ailments;
- Type 5 or Secondary Cardio Renal Syndromes: systemic abnormality leads to concurrent cardiac and renal dysfunction.3
Partial knowledge of pathophysiology of CRS explained that a decreased level of cardiac output is a primary clinical feature of cardiac heart failure, which causes reduction of renal perfusion and worsens renal function. Patients with acute decompensated heart failure have worsened renal functioning without hampering left ventricular ejection fraction.
This illustration supports renal functioning impairment with preserving blood flow to the kidneys. Therefore, this pathophysiology is not completely explanatory, but other factors involvements like also RAAS (renin-angiotensin-aldosterone system), the involvement of multiple chemicals like prostaglandins, nitric oxide [NO], endothelins, natriuretic peptides etc, accumulation of free radicals and stimulation of sympathetic activity have scope to progress cardio renal syndrome 1,4,5.
The diagnosis of Cardiorenal syndrome is critical, as there is a lot of chance to mislead. In the case of Cardiorenal syndrome, there is no association present between serum creatinine and Glomerulus Filtration Rate (GFR).The prognosis of heart failure patients depends upon ejection force decline with reduced GFR.
Measurement of serum creatinine alone does not provide an accurate report of the disease prognosis but can cause mislead. Patients with acute cardiac heart failure syndrome usually have decreased GFR or creatinine clearance, even with comparatively normal levels of serum creatinine.
Glomerulus Filtration Rate estimation is very important, as it helps to draw a general prognosis and useful to decide a treatment plan.
The measurement of cardiac output is not considered as a reliable indicator of Cardiorenal syndrome, as mostly it is normal in the level of Cardiorenal syndrome. However, the occurrence of low filling pressures, a decreased cardiac index or even reduced renal perfusion is not compulsory to detect CRS6.
The management of Cardiorenal Syndrome is clinically critical issue. There is no specific treatment modalities are applicable for all cases. Depending upon the patient condition and co-morbidities treatment plan is made. Following are different therapeutic agents use to treat Cardiorenal syndrome.
Diuretics is already established therapeutic agent in the management of patients with Cardiorenal syndrome. Different classified diuretics like thiazides, loop diuretics, and potassium-sparing diuretics can provide quick diuresis and natriuresis effects and useful for controlling short-term symptomatic relief. But long term diuretic therapy is not recommended, as it worsens the cardiovascular condition and increases the risk of cardiac mortality.
Low dose Dopamine
Usually, doctors are prescribed a low dose of dopamine in mild to moderate kidney function impairment. But no research-based evidence support this combination can provide extra benefits.
The symptoms associated with Cardiorenal syndrome is due to decrease cardiac output. Inotropes can be prescribed in combination with dopamine. But long term therapy provides a negative impact on overall survival rate.
Acute symptoms of Cardiorenal syndrome with the extremely edematous condition can be managed by ultrafiltration. This therapeutic approach assists in lowering down body weight quickly. But ultrafiltration is not applied in chronic Cardiorenal syndrome.
ACE inhibitors can improve cardiac heart failure condition, and also useful to reduce renal dysfunction at a lower dose. But higher dose can increase serum creatinine level and provides the harmful effect.
Arginine vasopressin receptor antagonists
This is a novel therapeutic agent provides considerable body weight reduction, edema reduction, and improves in dyspnea.
Adenosine A1 receptor antagonists
Increased level of adenosine causes renal dysfunction in a patient with cardiac heart failure. Adenosine A1 receptor antagonists provide diuresis and natriuresis with protecting renal function.
Use of hypertonic saline with diuretics
Using of hypertonic saline, along with diuretics in patients with Cardiorenal syndrome inhibits the activation of neurohormonal systems in heart failure patients. In addition, this therapy can also significantly increases diuresis and natriuresis.
Targeted renal delivery of drugs
By using a simple bifurcated catheter the benefit infusion system can facilitate the administration of the drug directly to the renal arteries. In this procedure concentrated the amount of drug reached in renal system and improves renal functioning. Simultaneously, renal first-pass elimination enhancement minimizes systemic serious adverse effects of provided drug1.
The poor prognosis reported with patients suffering from Cardiorenal syndrome. Multiple factors are responsible for poor prognosis, like
- Unclear pathophysiology
- Unspecified Treatment modalities
- Increased level of serum creatinine
- Decrease in creatinine clearance along with oliguria, hyponatremia, edema and side effects of diuretics
- Both renal dysfunction and heart failure worsens the prognosis of each other1,7.
- Narayan Pokhrel, Najindra Maharjan, Bismita Dhakal, Rohit R Arora; Cardiorenal syndrome: A literature review; Exp Clin Cardiol. 2008 Winter; 13(4): 165–170; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663478/
- Michael S Kierman, James E Udelson et.al; ardiorenal syndrome: Prognosis and treatment;://www.uptodate.com/contents/cardiorenal-syndrome-prognosis-and-treatment
- Andrew A. House, Inder Anand, Rinaldo Bellomo et.al.; Definition and classification of Cardio-Renal Syndromes: workgroup statements from the 7th ADQI Consensus Conference; Nephrol. Dial. Transplant. (2010)25 (5): 1416-1420.doi: 10.1093/ndt/gfq136First published online: March 12, 2010; http://ndt.oxfordjournals.org/content/25/5/1416.long
- Mahon NG, Blackstone EH, Francis GS, et al. The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure. J Am Coll Cardiol. 2002;40:1106–13.
- Yancy CW, Lopatin M, Stevenson LW, et al. ADHERE Scientific Advisory Committee and Investigators. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: A report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006;47:76–84.
- Francis G. Acute decompensated heart failure: The cardiorenal syndrome. Clev Clin J Med. 2006;73(Suppl 2):S8–13.
- Gottlieb SS, Abraham W, Butler J, et al. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail. 2002;8:136–41.