Rebecca Quinn, DVM, DACVIM (Internal Medicine and Cardiology)
Cardiorenal-anemia syndrome (CRAS) is a well-established condition in the human medical community. While CRAS has been recognized clinically in veterinary medicine for quite some time, in-depth discussions and research regarding patients suffering from CRAS have only just begun. In this syndrome, dysfunction of either the cardiac or renal system leads to deterioration of the other, in addition to anemia. This sets up a vicious cycle, whereby anemia leads to tissue hypoxia and further insult to both the heart and the kidneys.1 Research in human patients has clearly indicated that patients with CRAS compared to those with congestive heart failure (CHF) alone have much higher mortality rates.2 It is important that we now start exploring CRAS in more detail in order to develop treatment plans that help promote improved qualities of lives and prognoses for our patients.
The ACVIM Consensus Classes and the International Small Animal Cardiac Health Council (ISACHC) scores are often used to describe and classify cardiac disease.3,4 The International Renal Interest Society (IRIS) has created categories to assess patients for acute kidney injury (AKI), chronic kidney disease (CKD), and systemic hypertension.5 With the aid of these guidelines, as well as clinical signs, physical exam findings, and diagnostic test results (including systemic blood pressure, packed cell volume, and total solids), identifying patients with CRAS is possible. One can then use the combined information to determine what type of CRAS is occurring. Five types of CRAS have been described and are defined below.6,7
Type 1: Acute cardiorenal syndrome: Sudden cardiac dysfunction leading to AKI
- Examples may include acute heart failure, as in a dog with chronic degenerative valve disease (CVD) and a ruptured chordae tendinae, infectious aortic endocarditis, or sustained ventricular tachycardia.
- Decreased left-sided heart function leads to decreased kidney perfusion.
- CHF necessitates the use of diuretics, which worsens kidney function further.
- Identification of a heart murmur or arrhythmia, radiographic evidence of acute CHF, echocardiogram, ECG, and potentially biomarkers (cardiac troponin I and NT-proBNP) may help identify acute cardiac dysfunction.
- Early elevations in symmetrical dimethylarginine (SDMA) and later elevations in serum creatinine and BUN allow for recognition of AKI.
Type 2: Chronic Cardiorenal syndrome: Chronic cardiac disease leading to CKD
- Examples may include advanced CVD, dilated cardiomyopathy, or hypertrophic cardiomyopathy
- Chronically reduced cardiac function leads to decreased kidney perfusion and kidney congestion
- The chronic cardiac state leads to release of hormones such as angiotensin, endothelin, and epinephrine, which can further stress the cardiac and renal systems
- Medications such as diuretics and angiotensin converting enzyme inhibitors can lead to hypovolemia and low blood pressure
- Decompensation of preexisting heart disease can be identified by use of thoracic radiographs, echocardiogram, and serial NT-proBNP measurements
- Chronic kidney disease is most often identified by assessing serial creatinine and BUN levels; imaging such as abdominal ultrasound or glomerular filtration rate (GFR) may also be used to assess chronic kidney dysfunction.
Type 3: Acute renocardiac syndrome: Sudden renal dysfunction leading to acute cardiac dysfunction
- Examples may include toxicities, leptospirosis, pyelonephritis, or ureteral obstruction
- AKI often results in volume overload, electrolyte disturbances, and hormone activation. This combination of factors negatively impacts the heart by means of cardiac muscle depression, pro-arrhythmic effects, and cardiac inflammation (myocarditis)
- Diagnostics such as leptospirosis testing, urine culture, and CT scan may be used to identify the cause of AKI
- Changes in physical exam (identification of a new heart murmur or arrhythmia), thoracic radiographs, and echocardiogram can help identify acute cardiac dysfunction. Sudden increases in biomarkers such as cardiac troponin I and NT-proBNP may also help identify cardiac insult.
Type 4: Chronic renocardiac syndrome: Chronic renal disease leading to chronic cardiac dysfunction
- Common examples include interstitial nephritis and glomerulonephritis
- Chronic kidney disease may also be associated with anemia, systemic hypertension, or electrolyte imbalances
- The combination of chronic reduced renal function and persistent anemia can result in left ventricular hypertrophy, and poor systolic function.
- In cases of chronic renal disease, urine protein:creatinine, renal ultrasound, renal biopsy, and GFR studies may help identify the cause of disease
- Chronic cardiac dysfunction often requires longterm rechecks with thoracic radiographs, echocardiogram, and sometimes biomarkers to follow progression and identify decompensation.
Type 5: Secondary cardiorenal syndrome: Acute or chronic disease resulting in secondary cardiac and renal dysfunction.
- This may include endocrine disease (hyperthyroidism, hyperadrenocorticism, diabetes mellitus), sepsis, auto-immune or inflammatory diseases
- Systemic, metabolic, and endocrine diseases are associated with release of hormones, inflammatory cytokines, poor perfusion, and alteration in volume status that can affect both cardiac and renal function
- Patients suffering from Type 5 CRAS often require initial aggressive diagnostic testing and longterm follow up to ensure the primary condition is well managed and secondary cardiac and renal conditions are treated appropriately
Additional valuable information regarding CRAS was recently published by the Journal of Small Animal Practice.8 In this consensus statement, cardiac and renal diseases are discussed more thoroughly, and CRAS was described in more detail. In addition, thirteen consensus statements were presented with the goal of helping clinicians identify CRAS, improve diagnostic plans, and treat CRAS patients. At this point in time, established treatment protocols for veterinary CRAS patients do not exist. Treatment is instead tailored to each patient based on the type of CRAS and the predominant clinical signs. For instance, a patient with acute decompensation of chronic interstitial nephritis and a history of CHF may require adjustments in blood pressure medication, reduction in diuretic doses, conservative fluid therapy, electrolyte supplementation, and blood products to counterbalance anemia. While historically many clients were told their CRAS pets had poor prognoses, information gathered from our human counterparts suggest that some patients can achieve successful “balance” between their cardiac and renal diseases, if only for a short time. As the topic of CRAS becomes moves further into the veterinary spotlight, we may remain hopeful that additional research will shed light on diagnostic protocols and therapeutic options to optimally treat our patients.
For more information, please contact Dr. Rebecca Quinn at email@example.com, send a message to the general Cardiology inbox at firstname.lastname@example.org, or call the Cardiology Service at 617-541-5038.
- Iania A et al. Therapy insight: congestive heart failure, chronic kidney disease and anemia, the cardio-renal-anemia syndrome. Nat Clin Pract Cardio Med (2005) 2:2, 95.
- Efstratiadis G et al. Cardio-renal anemia syndrome. Hippokratia (2008) 12; 1: 11-16.
- Atkins C et al. Guidelines for the diagnosis and treatment of canine chronic degenerative valvular heart disease. JVIM (2009) 23:1142-1150.
- Woodbridge NJ. International Small Animal Cardiac Health Council. Recommendations for the diagnosis and treatment of heart failure in small animals.ISACHC Publication (1994) 5.
- Berl T et al. Kidney-heart interactions: epidemiology, pathogensis, and treatment. Clin J Am Soc Nephrol (2006) 1: 8 – 18.
- Ronco C et al. Cardiorenal syndrome. J Am Coll Cardiol (2008) 52: 1527 – 1539.
- Pouchelon JL et al. Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement. JSAP (2015) 56: 537-552.