Why does Furosemide (Lasix) cause metabolic alkalosis and elevated Blood Urea Nitrogen (BUN)?

From the Guidelines

Lasix (furosemide) causes metabolic alkalosis and elevated BUN through its mechanism as a loop diuretic, leading to increased excretion of sodium, chloride, potassium, and water, and ultimately resulting in contraction alkalosis and decreased renal perfusion. This diuretic effect is well-documented in the literature, with a study published in the British Journal of Pharmacology in 2018 1 highlighting the potential detrimental effects of loop diuretics on renal function. The study notes that the use of loop diuretics, such as furosemide, is associated with more severe renal decline, higher risk of hospital admission, and increased mortality rate.

The mechanism by which Lasix causes alkalosis and elevated BUN can be broken down into several key points:

• Lasix inhibits the sodium-potassium-chloride cotransporter in the ascending loop of Henle, leading to increased excretion of sodium, chloride, potassium, and water.
• The diuretic effect causes alkalosis through two main mechanisms: contraction alkalosis and increased hydrogen ion secretion.
• As Lasix promotes water loss, the extracellular fluid volume contracts, concentrating bicarbonate in the blood and raising pH.
• The increased sodium delivery to the distal tubule enhances sodium reabsorption in exchange for potassium and hydrogen ions, further contributing to alkalosis.
• The elevated BUN occurs because Lasix reduces blood volume and renal blood flow, decreasing glomerular filtration rate, and leading to a proportionally greater retention of urea nitrogen compared to creatinine.

It is worth noting that the 2018 study published in the British Journal of Pharmacology 1 provides more recent and higher-quality evidence compared to the 2004 study published in Hepatology 1, and therefore takes precedence in informing our understanding of the effects of Lasix on renal function and electrolyte balance.

From the FDA Drug Label

As with any effective diuretic, electrolyte depletion may occur during furosemide therapy, especially in patients receiving higher doses and a restricted salt intake Hypokalemia may develop with furosemide, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives. All patients receiving furosemide therapy should be observed for these signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia) Reversible elevations of BUN may occur and are associated with dehydration, which should be avoided, particularly in patients with renal insufficiency

Furosemide can cause hypochloremic alkalosis and elevated BUN due to:

• Electrolyte depletion, particularly hypokalemia, which can occur with brisk diuresis, inadequate oral electrolyte intake, or concomitant use of certain medications
• Dehydration, which can lead to reversible elevations of BUN and should be avoided, especially in patients with renal insufficiency 2, 3, 3

From the Research

Mechanism of Lasix-Induced Alkalosis and Elevated BUN

• Lasix, also known as furosemide, is a loop diuretic that can cause metabolic alkalosis and elevated Blood Urea Nitrogen (BUN) due to its mechanism of action 4, 5.
• Furosemide increases urinary sodium, potassium, and chloride losses, leading to hypochloremia and metabolic alkalosis 4.
• The reduction in extracellular volume and the subsequent activation of the renin-aldosterone axis can also contribute to the development of metabolic alkalosis 6.
• Additionally, furosemide can cause a decrease in blood chloride levels, which can further contribute to the development of metabolic alkalosis 4.

Electrolyte Imbalances and Alkalosis

• Hypokalemia is a common side effect of furosemide use, and it can contribute to the development of metabolic alkalosis 7, 6, 8.
• The loss of potassium and chloride ions in the urine can lead to a decrease in the production of hydrogen ions, resulting in metabolic alkalosis 5.
• The use of furosemide can also lead to an increase in sodium excretion, which can contribute to the development of hypovolemia and subsequent metabolic alkalosis 4.

Renal Effects and BUN Elevation

• Furosemide can cause a decrease in renal blood flow and an increase in renal vascular resistance, leading to an elevation in BUN 5.
• The reduction in extracellular volume and the subsequent decrease in renal perfusion can also contribute to the elevation of BUN 6.
• The use of furosemide can also lead to an increase in urinary sodium and chloride losses, which can contribute to the development of prerenal azotemia and subsequent elevation of BUN 4.