Cardiorenal Syndrome

Article Author:
Omar Kousa
Ryan Mullane

Article Editor:
Ahmed Aboeata

Editors In Chief:
Kranthi Sitammagari
Mayank Singhal

Managing Editors:
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Carrie Smith
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Patrick Le
Anoosh Zafar Gondal
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John Shell
Matthew Varacallo
Heba Mahdy
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Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon

9/13/2019 12:17:34 PM


The definition of cardiorenal syndrome is “any acute or chronic problem in the heart or kidneys that could result in an acute or chronic problem of the other.”[1]  The term describes multiple underlying subtypes, which subdivide according to the underlying triggering pathology and chronicity.


There are five subtypes of cardiorenal syndrome:

  • Type 1: a sharp decline in cardiac function that results in an acute decrease in renal function.
  • Type 2: chronic cardiac dysfunction that results in a sustained reduction in renal function.
  • Type 3: a sharp decline in renal function that results in an acute reduction in cardiac function.
  • Type 4: a chronic decline in kidney function that results in chronic cardiac dysfunction.
  • Type 5: systemic diseases that result in both cardiac and renal dysfunction.

Each type has its unique pathophysiology with unique management strategies and varying prognoses.[2][3] Cardiorenal syndrome type 1 is the commonest and most analyzed type. 


The 2007 report on the 118465 patients admitted with acutely decompensated heart failure in the ADHERE database showed that 9.0% of patients had normal renal function on admission whereas 27.4% had mild renal dysfunction (defined as GFR 60 to 89 mL-min-1.73 m), 43.5% had moderate renal dysfunction (GFR 30 to 59 mL-min-1.73 m), 13.1% had severe renal dysfunction (GFR 15 to 29 mL-min-1.73 m), and 7.0% had a GFR less than 15 mL-min-1.73 more were on chronic dialysis.[4][5] Other large databases have shown that the prevalence of cardiac or renal dysfunction increases the incidence of the other.


Type 1 cardiorenal syndrome occurs when there is acute decompensation of cardiac function leading to a decrease in glomerular filtration. Researchers have previously proposed a decline in cardiac output with decreased renal perfusion as the leading underlying cause for worsening kidney function in cardiorenal syndrome types 1 and 2.  However, recent studies have postulated that increased central venous pressures are a more critical factor.[1] When patients develop fluid overload due to worsening cardiac function, venous pressures increase and are transmitted back to the efferent arterioles; this results in a net decrease in the glomerular filtration pressure and renal injury. Other factors involved in the pathogenesis of types 1 and 2 cardiorenal syndromes include elevated intraabdominal pressures, activation of the renin-angiotensin-aldosterone system (RAAS), activation of the sympathetic nervous syndrome and increased inflammatory damage to the kidney related to heart failure.[6][7] So, targeting this cycle will be the mainstay of therapy for type 1 cardiorenal syndrome. Types 3 and 4 cardiorenal syndromes more likely the result from volume overload from renal dysfunction, abnormal cardiac function in the setting of metabolic disturbances (such as acidemia) and neurohormonal changes that accompany renal disease.[8] Patients can develop type 5 cardiorenal syndrome in the setting of sepsis, systemic lupus erythematosus (SLE), diabetes mellitus, decompensated cirrhosis, or amyloidosis; all of these disorders can lead to disease in both the heart and kidney.[9]

History and Physical

The patient’s history and physical exam can help clinicians to differentiate between acute and chronic decompensation as well as primarily cardiac or renal causes. Examples of helpful historical information would include if the patient presents with an acute myocardial ischemic event which can be triggering for severe cardiac dysfunction results in renal injury or recent onset diarrhea and vomiting causing acute renal injury which might lead to a sharp decline in heart function. Other historical clues such as medication use and prior labs (such as creatinine) may be helpful.[1] Although the clinical examination may not help differentiate the different types of cardiorenal syndrome, many patients will have evidence of volume overload with signs, including[1]:

  • Elevated jugular venous pressure
  • Generalized swelling and edema with “third spacing” presenting as pleural effusion(s), ascites or peripheral edema
  • Crackles or rales on lung auscultation
  • Patients may also demonstrate manifestations of decreased cardiac output with hypotension, fatigue, diminished peripheral pulses, and abnormal heart rates (either tachycardia or bradycardia)

Other possible signs indicating a primary renal cause of cardiorenal syndrome may include:

  • Pallor from anemia
  • Monitoring oliguria or anuria preceding cardiac dysfunction


Initial history and physical examination could tailor the provider's approach towards the appropriate investigation for determining the underlying etiology. The initial laboratory workup should include a complete blood count (CBC), complete metabolic panel (CMP), urine studies (urinalysis with microscopy, urine protein to creatinine ratio, urine sodium), brain natriuretic peptide (BNP), and troponin. The estimated glomerular filtration rate (eGFR) is calculable from the creatinine level to help determine the degree of renal impairment. In patients with possible cardiorenal syndrome type 5, further investigations including blood & urine cultures, lupus serologies (antinuclear antibody [ANA], anti-double-stranded DNA, serum complement levels [C3, C4]), and a procalcitonin may be useful. An electrocardiogram and cardiac monitoring should be included in the initial evaluation to evaluate for any underlying arrhythmias that may be contributing to or resulting from the cardiorenal syndrome. A transthoracic echocardiogram is invaluable in evaluating for wall motion abnormalities, obtaining measurements such as the left ventricular ejection fraction (LVEF), and determining whether or not there is a pericardial effusion. A renal ultrasound can help evaluate kidney size and function. Smaller kidney disease and increased renal echogenicity are consistent with chronic kidney disease.[7]

Treatment / Management

Although no therapies have been demonstrated to improve outcomes in patients with the cardiorenal syndrome, treatment generally is directed at the underlying etiology and to improve the complications of the syndrome as most patients with cardiorenal syndrome have volume overload, the primary treatment targets typically fluid removal either with diuretics or ultrafiltration.[1] Loop diuretics, including furosemide, torsemide, and bumetanide are the most potent diuretic class; they can be used alone or in conjunction with other types of diuretics. There are two strategies, either a continuous infusion dose or using intravenous boluses. Creatinine clearance can be used to help determine the dosage. For example, treatment can start with loading dose of 40 mg intravenous furosemide loading dose followed by 10 mg/hr if the creatinine clearance is between 25 and 75 mL/min, whereas you can start with 80 mg to 160 mg intravenous furosemide as maximum dose that can be repeated several times a day to achieve a desirable response for the same creatinine clearance.[1][5] Definitive clinical evidence is still lacking to support either strategy over the other. However, using the continuous infusion strategy would give clinicians more opportunities to evaluate on an hourly basis the response to therapy. Also, adding a thiazide diuretic can help overcome diuretic resistance in some cardiorenal patients, with metolazone typically used, and it is considered one of the most common combinations with loop diuretics. On the other hand, ultrafiltration can be useful in resistive cases, but recent studies showed that diuretic therapy was better than ultrafiltration for symptom control and creatinine level decline in the initial approach towards obtaining euvolemia. Inotropes can be used for refractory cases and can help to improve cardiac function and decrease venous congestion. Unfortunately, no conclusive data has supported there use in cardiorenal syndrome.[2][7] On the other hand, treatment of cardiorenal syndrome type 3 and 4 would target treating underlying kidney disease and avoiding nephrotoxic medications and contrast. Finally, treatment of the underlying systemic cause would be the treatment of type 5 cardiorenal syndrome, for example, using antibiotics for sepsis. 

Differential Diagnosis

It is difficult to determine the etiology of the cardiorenal syndrome on initial presentation in many patients as they might present without all the classic features, making the diagnosis challenging. History of a recent increase in diuretic doses, diarrhea, vomiting, skin or throat infection, heatstroke, fever, recent extensive workout or non-steroid anti-inflammatory drug (NSAID) use can help towards a hypovolemic etiology.


The overall prognosis is poor. There are multiple mortality and readmission predictor calculators available to predict the individual patient’s prognosis further. They use multiple variables to predict in-hospital mortality and readmission rate, including the blood urea nitrogen (BUN), systolic blood pressure, serum creatinine, brain natriuretic peptide, and response to diuretics.[10][11][12]


  • Liver failure
  • Respiratory failure requiring invasive and non-invasive ventilation
  • Worsening renal failure requiring dialysis (either temporarily or permanently)

Deterrence and Patient Education

Medications (diuretics) and diet compliance, tracking body weight with regular interval follow up in heart failure clinic to optimize outpatient diuretic doses are crucial preventive factors for recurrence.

Enhancing Healthcare Team Outcomes

Close follow-up after hospital discharge, preferably within a few days to track patient’s weight, symptoms, and labs would help to decrease cardiorenal syndrome readmission rates. Moreover, well-established communication plans between the interprofessional team members, including and not limited to cardiology, nephrology and hospitalist service with primary care providers and nurse practitioners may help decrease future exacerbations and improve the patient’s experience. Specialty care nurses are involved in providing treatments, monitoring patients, educating patients and their families, and provide feedback to the team. Pharmacists review medications prescribed, drug-drug interactions, and provide education. Cardiorenal syndrome requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]

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Cardiorenal Syndrome - Questions

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A 74-year-old man with a history of diabetes, ischemic cardiomyopathy, hypertension, and coronary artery diseases presents to the emergency department for cough. Symptoms started three days ago after he came back from a two-week vacation in Mexico. He was not compliant with medications or cardiac diet while he was there. He noticed that his weight increased by 4 kilograms. Home medications are sitagliptin, lisinopril, metoprolol, atorvastatin, furosemide, and aspirin. On physical examination, blood pressure is 102/57 mmHg, pulse 110 beats/min, temperature 37.3 C and oxygen saturation 88% on room air. Chest examination shows bilateral crackles, and he has pitting edema in his ankles. The rest of the examination is unremarkable. Laboratory studies show creatinine 1.8 mg/dL (baseline is 0.9 mg/dL), with an estimated glomerular filtration rate (eGFR) of 55 mL/min/ 1.73 m2 and troponin level was 0.1 ng/mL (normal baseline). A CT angiogram rules out pulmonary embolism. He was started on intravenous fluid, and 10 hours later his oxygenation deteriorated, he was subsequently intubated, and he stopped producing urine for the last 12 hours. Which of the following is the most likely cause of deterioration in his clinical status?

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An 85-year-old man was hospitalized because of acute exacerbation of chronic obstructive lung disease secondary to lung infection. He has a history of chronic bronchitis, heart failure with reduced ejection fraction, hypertension and coronary artery disease. On the following night, his blood pressure dropped to 80/65 mm/Hg. He was started on a one-liter normal saline fluid bolus. After 30 minutes, his repeated blood pressure was 82/64 mm/Hg. On evaluation, the patient is feeling dizzy and not-fully comprehensive but denies any ongoing chest pain. Pulse is 85 /min and oxygen saturation 84% on room air. Chest examination shows bilateral fine crackles and jugular venous distention. The rest of the examination is unremarkable. The patient is started on oxygen therapy and his oxygen saturation improved to 90%. He is transferred to the intensive care unit, and bedside ultrasound shows dilated inferior vena cava. Bloodwork reveals worsened kidney function and elevated troponin. Which of the following is the next best step in the management of this patient?

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A 63-year-old female presents to the emergency department because of worsening shortness of breath and orthopnea that started two days ago. On arrival, she is afebrile, blood pressure is 102/61 mm Hg, heart rate 99 beats per minute, respiratory rate 27 breaths per minute, and oxygen saturation 82% on room air. Clinical examination reveals bilateral crackles, elevated jugular venous pressure, and bilateral pitting edema. Further history reveals a recent weight gain of 9 pounds. She was started on 5 L nasal oxygen, and her saturation improved to 92% on 5 L. She has a past medical history of diabetes, hypertension, hyperlipidemia and coronary artery disease. She is on aspirin, simvastatin, torsemide, and insulin. Her labs showed brain natriuretic peptide of 1500 and glomerular filtration rate (eGFR) of 33 mL/min/ 1.73 m2. Which of the following is the next best step in the management of this patient?

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A 59-year-old man with a history of HIV infection, hypothyroidism, hepatitis C infection, and hypertension presents to the emergency department for a productive cough and fever. His initial vital signs showed a temperature of 38.1 C, heart rate 111 bpm, oxygen saturation 88% and blood pressure 103/54 mmHg. A chest radiograph reveals right lower lobe opacity. His labs show white blood cell count of 11,000 cell/mm3, creatinine of 1.8 mg/dL, troponin level was 0.4 ng/mL and brain natriuretic peptide of 550 pg/ml. The patient admits to nonadherence with his HIV treatment. His labs one month ago showed creatinine of 0.9 mg/dL, troponin level was 0.03 ng/mL and brain natriuretic peptide 75 pg/m. Bedside echocardiogram shows reduced ejection fraction compared to last transthoracic echocardiogram he had nine months ago. His condition deteriorates in the emergency department, was requiring more oxygen and eventually intubation secondary to worsening respiratory failure. Which of the following would most likely improve his cardiac function in the long term?

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A 23-year-old man marathon runner, who was participating in a triathlon, presented to the emergency department for nausea and vomiting. In the emergency department, his vital signs showed a heart rate of 140/min and blood pressure 95/76 mmHg. Clinical examination showed dry lips, mouth, and skin. His labs showed a white blood cell count of 7,000 cells/mm3, hemoglobin 15 g/dL, platelets 450,000/microL, sodium 141 mEq/L, potassium 5.1 mmol/L, creatinine 5 mg/dL, CO2 17 mEq/L. He was given one-liter fluid bolus and discharged from the emergency department. The following day he came again to the hospital because of worsening vomiting and bloody urine. His repeated labs show a white blood cell count of 12,000 cells/mm3, hemoglobin 16 g/dL, platelets 456,000/microL, sodium 142 mEq/L, potassium 5 mmol/L, creatinine 2.0 gm/dL, CO2 15 mEq/L. Urinalysis shows a red color, pH 4.8, 2-3 RBCs, blood positive, nitrate negative and no bacteria. He is admitted to the hospital and give IV fluids. A few days later, he became hypoxic and was eventually intubated. Clinical examination reveals elevated jugular venous pressure, bilateral crackles and bilateral pitting edema. Which of the following best explains his recent decline in cardiac function?

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Cardiorenal Syndrome - References


Thind GS,Loehrke M,Wilt JL, Acute cardiorenal syndrome: Mechanisms and clinical implications. Cleveland Clinic journal of medicine. 2018 Mar;     [PubMed]
Hadjiphilippou S,Kon SP, Cardiorenal syndrome: review of our current understanding. Journal of the Royal Society of Medicine. 2016 Jan;     [PubMed]
Ronco C,Haapio M,House AA,Anavekar N,Bellomo R, Cardiorenal syndrome. Journal of the American College of Cardiology. 2008 Nov 4;     [PubMed]
Heywood JT,Fonarow GC,Costanzo MR,Mathur VS,Wigneswaran JR,Wynne J, High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. Journal of cardiac failure. 2007 Aug;     [PubMed]
Takahama H,Kitakaze M, Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets. American journal of physiology. Heart and circulatory physiology. 2017 Oct 1;     [PubMed]
Di Lullo L,Bellasi A,Barbera V,Russo D,Russo L,Di Iorio B,Cozzolino M,Ronco C, Pathophysiology of the cardio-renal syndromes types 1-5: An uptodate. Indian heart journal. 2017 Mar - Apr;     [PubMed]
Smith GL,Lichtman JH,Bracken MB,Shlipak MG,Phillips CO,DiCapua P,Krumholz HM, Renal impairment and outcomes in heart failure: systematic review and meta-analysis. Journal of the American College of Cardiology. 2006 May 16;     [PubMed]
Hillege HL,Nitsch D,Pfeffer MA,Swedberg K,McMurray JJ,Yusuf S,Granger CB,Michelson EL,Ostergren J,Cornel JH,de Zeeuw D,Pocock S,van Veldhuisen DJ, Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006 Feb 7;     [PubMed]
Aronson D,Mittleman MA,Burger AJ, Elevated blood urea nitrogen level as a predictor of mortality in patients admitted for decompensated heart failure. The American journal of medicine. 2004 Apr 1;     [PubMed]
Schrier RW,Abraham WT, Hormones and hemodynamics in heart failure. The New England journal of medicine. 1999 Aug 19;     [PubMed]
Chuasuwan A,Kellum JA, Cardio-renal syndrome type 3: epidemiology, pathophysiology, and treatment. Seminars in nephrology. 2012 Jan;     [PubMed]
Mehta RL,Rabb H,Shaw AD,Singbartl K,Ronco C,McCullough PA,Kellum JA, Cardiorenal syndrome type 5: clinical presentation, pathophysiology and management strategies from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contributions to nephrology. 2013;     [PubMed]


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