What is urea?

Urea: Definition, Functions, and Clinical Significance

Urea is the primary nitrogenous end product of protein metabolism in humans, produced in the liver through the urea cycle and excreted primarily by the kidneys. It serves multiple physiological functions and has significant clinical applications in medicine and dermatology.

Biochemical Nature and Production

Urea (CO(NH₂)₂) is generated by the urea cycle enzymes, which are predominantly expressed in the liver but also present at lower levels in other tissues 1. It represents the final metabolic pathway for eliminating nitrogen from amino acid catabolism:

• Produced in the liver as the degradation product of nitrogenous or protein materials
• Serum amino acids and proteins in both serum and skeletal muscle serve as nitrogen sources 2
• Enters the bloodstream after production and is primarily eliminated through urine

Physiological Functions

Urea serves several important physiological roles:

• Fluid Balance Marker: Helps maintain proper fluid balance in the body 2
• Nitrogen Elimination: Primary mechanism for excreting excess nitrogen from protein metabolism
• Skin Hydration: Component of the natural moisturizing factor (NMF) in the epidermis, essential for adequate hydration and integrity of the stratum corneum 3
• Keratinocyte Regulation: Plays a fundamental role in regulating keratinocyte proliferation and differentiation 3

Clinical Significance

Renal Function Assessment

Blood Urea Nitrogen (BUN) has been utilized to evaluate renal function for decades 1:

• In heart failure, BUN is a marker of both congestion and cardiac/renal dysfunction 2
• Unlike creatinine (which primarily reflects GFR), urea is both filtered and reabsorbed in the kidneys
• Approximately 40-50% of filtered urea is reabsorbed, predominantly in the proximal tubule 2
• BUN has been found to be a better predictor of outcome than creatinine or estimated GFR in acute heart failure 2

Fractional Excretion of Urea (FEUrea)

• FEUrea <28.16% may indicate pre-renal etiology with a sensitivity of 75% and specificity of 83% in patients with cirrhosis and AKI 4
• More useful than FENa in patients receiving diuretics, with higher specificity (82% vs 44%) 4
• Formula: [(Urine urea × Serum creatinine) / (Serum urea × Urine creatinine)] × 100 4

Dialysis Applications

• Residual kidney function can be assessed through urea clearance in dialysis patients 4
• Urea reduction ratio (URR) ≥0.67 provides a simplified means of assessing adequacy of intermittent hemodialysis 4
• In dialysis patients, achieving URR >25% is associated with better outcomes 4

Dermatological Applications

Urea has multiple beneficial properties for skin health 3, 5:

• Emollient: Provides moisturizing effects for dry skin conditions
• Keratolytic: At higher concentrations (>10%), breaks down keratin, useful for thick, scaly skin
• Skin Barrier Enhancement: Improves skin barrier function and antimicrobial defense
• Penetration Enhancer: Increases skin penetration of other topical medications
• Antimicrobial Properties: Exhibits some antibacterial activity

Effective for treating:

• Ichthyosis, xerosis, atopic dermatitis
• Psoriasis and seborrheic dermatitis
• Onychomycosis and dystrophic nails
• Keratosis and pruritus

Potential Adverse Effects

• In high concentrations, urea may contribute to cardiovascular disease in chronic kidney disease patients 6
• Topical applications are generally well-tolerated with mild irritation being the most common side effect 7, 5
• At very high concentrations, urea can cause uncoiling of DNA in vitro, though this doesn't translate to in vivo genotoxicity 7

Monitoring Considerations

• In athletes, urea has been historically considered as a marker reflecting acute and chronic workloads, particularly in high-volume, high-intensity endurance sports 2
• However, recent research indicates limited utility of blood urea measurement alone for monitoring training load in athletes 2
• In patients with heart failure, monitoring BUN can help assess congestion and guide diuretic therapy 2

Understanding urea's multifaceted role in human physiology provides valuable insights for clinical assessment and therapeutic applications across multiple medical specialties.