This article describes five kinds of cardiorenal syndrome, as well as its underlying causes, diagnostic techniques, and several treatment options. It emphasises how heart and kidney problems interact to treat this complicated illness.

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Introduction and definition

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. The term describes multiple underlying subtypes, which subdivide according to the underlying triggering pathology and chronicity. Each subtype involves a unique pathophysiology, and thus, the management strategy for each subtype is different management strategies

Classification

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

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Etiopathogenesis

Factors leading to Cardiorenal syndrome types 1 and 2:

• Low cardiac output leads to decreased renal perfusion
• Elevated Central venous pressures
• 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
• Elevated intra-abdominal pressures
• Activation of the renin-angiotensin-aldosterone system (RAAS)
• Activation of the sympathetic nervous syndrome
• Systemic inflammation

Factors leading to cardiorenal syndrome types 3 and 4:

• Volume overload from renal dysfunction
• Abnormal cardiac function in the setting of metabolic disturbances (such as acidemia)
• Neurohormonal changes that accompany renal disease

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Evaluation

History

The patient’s history and physical exam can help clinicians 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 that can trigger severe cardiac dysfunction, which subsequently results in renal injury or recent-onset diarrhoea 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 laboratory values (such as creatinine), may be helpful. 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.
2. Generalized swelling and oedema with “third spacing” presenting as pleural effusion(s), ascites, or peripheral oedema.
3. Crackles or rales on lung auscultation.
4. 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 anaemia
• Monitoring oliguria or anuria preceding cardiac dysfunction

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Laboratory evaluation

1. The initial laboratory workup should include a complete blood count (CBC), urine studies (urinalysis with microscopy, urine protein to creatinine ratio, urine sodium), brain natriuretic peptide (BNP), and troponin.
2. The estimated glomerular filtration rate (eGFR) is calculable from the creatinine level to help determine the degree of renal impairment.
3. 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.
4. 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.
5. 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.
6. A renal ultrasound can help evaluate kidney size and function. Smaller kidney disease and increased renal echogenicity are consistent with chronic kidney disease.

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Treatment

Although no therapies have been demonstrated to improve outcomes in patients with cardiorenal syndrome, treatment generally is directed at the underlying aetiology 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.

Loop diuretics, including furosemide and torsemide are the most potent diuretic class. They can be used alone or in conjunction with other types of diuretics. There are two strategies in terms of diuresis:  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 a 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. In contrast, one can start with 80 mg to 160 mg of intravenous furosemide as a maximum dose that can be repeated several times a day to achieve a desirable response for the same creatinine clearance.

Also, adding a thiazide diuretic can help overcome diuretic resistance in some cardiorenal patients. Metolazone is typically used and is considered one of the most common combinations with loop diuretics.

On the other hand, ultrafiltration can be useful in resistive cases. However, 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 improve cardiac function and decrease venous congestion. Unfortunately, no conclusive data have supported their use in cardiorenal syndrome.

On the other hand, the 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 conditions would be the treatment of type 5 cardiorenal syndrome.

A history of a recent increase in diuretic doses, diarrhoea, vomiting, skin or throat infection, heatstroke, fever, a recent extensive workout, or non-steroid anti-inflammatory drug (NSAID) use can help towards a hypovolemic aetiology.

The overall prognosis is poor. There are multiple mortality and readmission predictor calculators available to predict the individual patient’s prognosis.

They use multiple variables to predict in-hospital mortality and readmission rate, including blood urea nitrogen (BUN), systolic blood pressure, serum creatinine, brain natriuretic peptide, and response to diuretics.

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Complications

Liver failure

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

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bhavin Mandowara is a practising nephrologist at Zydus Hospital, Ahmedabad.