Cardiorenal Syndrome

Article Author:
Omar Kousa
Article Author (Archived):
Ryan Mullane
Article Editor:
Ahmed Aboeata
Updated:
9/13/2019 12:17:34 PM
PubMed Link:
Cardiorenal Syndrome

Introduction

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.

Etiology

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. 

Epidemiology

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.

Pathophysiology

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

Evaluation

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.

Prognosis

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]

Complications

  • 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]


References

[1] Thind GS,Loehrke M,Wilt JL, Acute cardiorenal syndrome: Mechanisms and clinical implications. Cleveland Clinic journal of medicine. 2018 Mar;     [PubMed PMID: 29522391]
[2] Hadjiphilippou S,Kon SP, Cardiorenal syndrome: review of our current understanding. Journal of the Royal Society of Medicine. 2016 Jan;     [PubMed PMID: 26609123]
[3] Ronco C,Haapio M,House AA,Anavekar N,Bellomo R, Cardiorenal syndrome. Journal of the American College of Cardiology. 2008 Nov 4;     [PubMed PMID: 19007588]
[4] 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 PMID: 17675055]
[5] 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 PMID: 28733448]
[6] Schrier RW,Abraham WT, Hormones and hemodynamics in heart failure. The New England journal of medicine. 1999 Aug 19;     [PubMed PMID: 10451464]
[7] 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 PMID: 28460776]
[8] Chuasuwan A,Kellum JA, Cardio-renal syndrome type 3: epidemiology, pathophysiology, and treatment. Seminars in nephrology. 2012 Jan;     [PubMed PMID: 22365160]
[9] 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 PMID: 23689662]
[10] 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 PMID: 16697315]
[11] 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 PMID: 16461840]
[12] 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 PMID: 15047036]