What are the benefits and harms of diuretic use in patients with nephrotic syndrome?

From the Guidelines

Diuretics should be used with caution in patients with nephrotic syndrome, as they can provide significant benefits in reducing edema and fluid overload, but also pose risks of electrolyte imbalances, acute kidney injury, and intravascular volume depletion. The use of diuretics in nephrotic syndrome is a complex issue, and their benefits and harms must be carefully weighed. Loop diuretics, such as furosemide, are the mainstay treatment for reducing edema and fluid overload, which are hallmark symptoms of nephrotic syndrome 1. These medications help manage hypertension, improve patient comfort, and may reduce the risk of complications like pleural effusions or ascites.

Benefits of Diuretics

The benefits of diuretics in nephrotic syndrome include:

• Reduction of edema and fluid overload
• Improvement of hypertension
• Enhancement of patient comfort
• Reduction of the risk of complications like pleural effusions or ascites According to the study by 1, diuretics can improve oedema and fluid control and enable fluid administration to provide adequate nutrition, especially when given in conjunction with albumin infusions.

Harms of Diuretics

However, diuretics can also cause significant harms, including:

• Electrolyte imbalances (particularly hypokalemia and hyponatremia)
• Acute kidney injury
• Intravascular volume depletion The risk of these harms is heightened in nephrotic patients due to their already compromised intravascular volume from hypoalbuminemia 1.

Optimal Use of Diuretics

For optimal use, diuretics should be started at lower doses with careful titration while monitoring renal function, electrolytes, and blood pressure 1. Combination therapy with albumin infusions may enhance diuretic efficacy in resistant cases by temporarily improving oncotic pressure. Thiazide diuretics can be added for synergistic effect in resistant edema. Potassium-sparing diuretics like amiloride may help minimize hypokalemia but require careful monitoring in patients with reduced kidney function 1.

Key Considerations

Key considerations in the use of diuretics in nephrotic syndrome include:

• Monitoring of renal function, electrolytes, and blood pressure
• Use of combination therapy with albumin infusions
• Addition of thiazide diuretics for synergistic effect
• Use of potassium-sparing diuretics like amiloride to minimize hypokalemia
• Careful monitoring in patients with reduced kidney function The underlying cause of nephrotic syndrome should be treated concurrently, as resolving the primary disease remains the definitive approach to managing fluid retention 1.

From the FDA Drug Label

Furosemide tablets are indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. The benefits of diuretic use, such as furosemide, in patients with nephrotic syndrome include:

• Treatment of edema associated with the condition
• The drug is particularly useful when an agent with greater diuretic potential is desired However, the harms are not explicitly stated in the label for patients with nephrotic syndrome. 2

From the Research

Benefits of Diuretic Use in Nephrotic Syndrome

• Diuretics assist in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia 3
• They play a significant role in the treatment of fluid overload in the body, including in nephrotic syndrome 4
• Diuretics can help manage oedema, a defining element of nephrotic syndrome, although treatment outcomes may vary considerably between clinicians 5

Harms of Diuretic Use in Nephrotic Syndrome

• Diuretic-related adverse events, such as biochemical disturbances involving the uric acid, Na(+), and K(+) axes, are not uncommon 3
• Patients with nephrotic syndrome may have subnormal responses to diuretics, requiring larger doses or more frequent administration 6
• Diuretic resistance may occur in patients with chronic renal insufficiency or nephrotic syndrome, limiting the effectiveness of diuretic therapy 7
• Binding of loop diuretics to urinary albumin can curtail their action in the loop of Henle, reducing their effectiveness 7

Considerations for Diuretic Use in Nephrotic Syndrome

• The response of patients with nephrotic syndrome to diuretics is related to the dose and may be best described by a sigmoid curve 3
• A systemic approach for management is recommended, starting from thiazides and proceeding to loop diuretics 4
• Strategies to improve loop diuretic responsiveness include increasing diuretic dosage, concurrent use of a thiazide diuretic, and attempts to maximally reduce albumin excretion 7