What Drugs are Used to Decrease Urea Levels?

October 9, 2025 •

4 min read

High blood urea nitrogen (BUN) levels are often a sign of kidney or liver dysfunction, and their treatment is not always direct. This article explains what drugs are used to decrease urea levels by targeting the root causes or helping the body eliminate excess nitrogen, which ultimately reduces the urea burden.

Quick Summary

Treatment for high urea levels is not based on a single medication but varies by cause, such as urea cycle disorders or chronic kidney disease. Strategies include nitrogen scavengers and therapies that support kidney function or manage complications.

Key Points

Nitrogen Scavengers for UCDs: Medications like sodium phenylbutyrate and glycerol phenylbutyrate treat urea cycle disorders by promoting alternative pathways for nitrogen excretion, reducing the toxic ammonia that precedes urea formation.
SGLT2 Inhibitors for CKD: These drugs, such as dapagliflozin and empagliflozin, protect kidney function by lowering pressure within the glomeruli, slowing the progression of chronic kidney disease and managing urea levels over time.
Ketoanalogues Supplement Low-Protein Diets: Alpha-ketoanalogues like Ketosteril are used in conjunction with low-protein diets in CKD patients to provide essential amino acids while decreasing blood urea nitrogen production.
Medications Manage Complications: For advanced uremia, other medications address symptoms and metabolic imbalances, such as anemia (EPO, iron), high potassium (potassium binders), and metabolic acidosis (sodium bicarbonate).
Dialysis for Severe Cases: When kidney function fails, dialysis is a life-sustaining medical procedure that directly filters waste products, including urea, from the blood.
Treatment is Cause-Dependent: Effective medication strategy is dictated by the underlying cause (UCD, CKD, or other conditions) and should always be determined by a healthcare professional.

The body produces urea as a waste product when it breaks down proteins. It is typically filtered from the blood by the kidneys and excreted in urine. High blood urea levels, or uremia, can result from kidney dysfunction or a compromised liver unable to complete the urea cycle. Therefore, the medical approach to decreasing urea levels depends entirely on the specific underlying condition. Medications can support an alternative nitrogen removal pathway, protect the kidneys, or manage related symptoms.

Medications for Urea Cycle Disorders (UCDs)

In individuals with UCDs, a genetic defect prevents the normal conversion of excess nitrogen into urea, leading to a buildup of toxic ammonia. Medications known as 'nitrogen scavengers' are crucial for creating an alternative route to excrete this waste nitrogen safely.

Sodium Phenylbutyrate (Buphenyl, Pheburane, Olpruva)

This is a foundational medication for managing UCDs. It is metabolized in the body into phenylacetate, which then conjugates with glutamine to form phenylacetylglutamine. This compound is rich in nitrogen and is easily excreted by the kidneys. This process essentially bypasses the faulty urea cycle.

Glycerol Phenylbutyrate (Ravicti)

Glycerol phenylbutyrate is a pro-drug that also works as a nitrogen-scavenging agent. It is broken down into phenylbutyrate, and then phenylacetate, which follows the same glutamine conjugation pathway as sodium phenylbutyrate. It is often preferred for long-term management due to its less unpleasant taste and odor compared to sodium phenylbutyrate.

Sodium Benzoate

This medication works by conjugating with glycine to form hippurate, which is then excreted by the kidneys. It provides another way to remove excess nitrogen from the body, independent of the urea cycle. It is often used in combination with sodium phenylacetate and arginine for acute hyperammonemic crises.

Medications for Chronic Kidney Disease (CKD)

For most CKD patients, the focus is not on direct urea removal but on slowing the progression of kidney damage, which helps keep urea levels in check. A primary intervention is to follow a low-protein diet, reducing the nitrogen load on the kidneys. Medications are used to control contributing factors like high blood pressure and diabetes, and to manage the resulting metabolic abnormalities.

SGLT2 Inhibitors (Dapagliflozin, Empagliflozin)

Initially developed for diabetes, these medications (ending in '-flozin') have shown significant kidney-protective benefits, even for non-diabetic patients with CKD. They work by reducing pressure on the glomeruli (the kidney's filtering units), which slows the decline of kidney function. By preserving kidney function, they help maintain the body's natural ability to excrete urea.

ACE Inhibitors and Angiotensin Receptor Blockers (ARBs)

These drugs are prescribed to control high blood pressure, a major cause of kidney damage. By relaxing blood vessels, they can help protect the kidneys and slow disease progression, thereby indirectly influencing urea levels by supporting renal function.

Alpha-Ketoanalogues (Ketosteril)

This nutritional supplement is used alongside a low-protein diet in CKD patients to provide essential amino acids without contributing a significant nitrogen load. By reducing protein metabolism, they help decrease blood urea nitrogen (BUN) levels. They have been shown to slow the progression of CKD.

Sodium Bicarbonate

Metabolic acidosis is a common complication of advanced CKD. Sodium bicarbonate can be used to treat this, which in turn can help improve kidney function and metabolic balance, including managing urea and potassium levels.

Medications for Uremic Complications

In cases of advanced uremia, medications are often used to treat the symptoms and related metabolic imbalances.

Anemia: Erythropoietin-stimulating agents (ESAs) like epoetin alfa, along with iron supplements, are used to treat anemia, a common complication of kidney failure.
Pruritus (itching): Phosphate binders (sevelamer, lanthanum) and gabapentin can manage the severe itching that may occur with uremia.
Nausea: Anti-nausea medications like ondansetron can be used to relieve symptoms.
Hyperkalemia: Sodium polystyrene sulfonate or newer agents can lower dangerously high potassium levels.

Dialysis and Other Approaches

For severe cases of kidney failure where medications are no longer sufficient, dialysis is the primary treatment to remove waste products like urea and excess fluid. This medical procedure mechanically filters the blood, providing immediate relief from uremic toxicity. Dietary adjustments, especially a low-protein diet, are also a cornerstone of managing urea levels for both UCD and CKD patients.

Comparison of Key Treatment Approaches


Feature	Nitrogen Scavengers	SGLT2 Inhibitors	Alpha-Ketoanalogues	Dialysis
Target Condition	Urea Cycle Disorders	Chronic Kidney Disease (CKD), especially with diabetes	Chronic Kidney Disease (CKD)	End-Stage Renal Disease (ESRD)
Primary Mechanism	Bypasses faulty urea cycle; promotes alternative nitrogen excretion pathways	Protects kidney function by reducing intraglomerular pressure	Reduces nitrogen load from protein metabolism; provides amino acids	Physically filters urea and waste products from blood
Effect on Urea	Indirectly reduces urea production by diverting nitrogen waste	Helps maintain kidney function, which manages urea long-term	Decreases blood urea nitrogen (BUN) by reducing protein breakdown	Removes urea and other toxins directly from the blood
Example Drugs	Sodium Phenylbutyrate, Glycerol Phenylbutyrate	Dapagliflozin, Empagliflozin	Ketosteril (Ketoanalogues)	Not a drug, but a procedure
Use Case	Chronic management of UCDs alongside a low-protein diet	Slowing CKD progression and managing comorbidities	Supplementing low-protein diets to reduce urea in CKD	Advanced kidney failure where kidneys cannot filter blood

Conclusion

Addressing high urea levels is a complex process that depends heavily on the underlying cause, whether it's a genetic disorder like a UCD or chronic kidney failure. Medications range from specialized nitrogen-scavenging agents that bypass the urea cycle to broader therapies that protect and maintain kidney function. In advanced cases, dialysis becomes the necessary intervention. For all conditions, proper dietary management is a cornerstone of treatment. Patients should consult a healthcare professional to determine the most appropriate and effective strategy for their specific needs, often involving a combination of medications and dietary changes. A helpful resource for those with kidney disease is the National Kidney Foundation, which provides comprehensive information on treatment options and safety measures.

Frequently Asked Questions

No single medication is available to directly remove urea from the blood. Treatments focus on either managing the underlying condition causing high urea levels or using mechanical filtration, like dialysis, for severe cases.

Nitrogen scavengers help the body eliminate nitrogen waste by an alternative route, bypassing the dysfunctional urea cycle. They conjugate with amino acids, and the resulting compound is excreted by the kidneys, which ultimately lowers the load of toxic ammonia and urea.

SGLT2 inhibitors like dapagliflozin don't directly decrease urea. Instead, they slow the progression of chronic kidney disease by protecting the kidneys, which helps the body maintain its natural ability to manage urea excretion over the long term.

Ketoanalogues, often used alongside a low-protein diet, provide essential amino acids to patients with chronic kidney disease. This reduces the amount of dietary protein the body needs to break down, thereby lowering the generation of nitrogen waste and blood urea nitrogen (BUN) levels.

Yes, controlling high blood pressure is vital for managing chronic kidney disease, a major cause of high urea. Medications like ACE inhibitors and ARBs help protect the kidneys from further damage, preserving their ability to filter waste.

If medications and dietary changes are insufficient, particularly in cases of severe kidney failure, dialysis is typically initiated. Dialysis is a procedure that mechanically filters urea and other waste products from the blood.

Dietary protein restriction is a key part of managing high urea, as it reduces the nitrogen load. However, medications may still be necessary, especially for genetic urea cycle disorders or advanced chronic kidney disease, to manage the underlying condition and prevent complications.