What is the significance of elevated Urea (Blood Urea Nitrogen) levels?

From the Guidelines

Urea is only a marker substance for the clinical condition known as uremia, and its levels should be interpreted in the context of their rates of change over time, rather than absolute levels. When considering urea in the context of renal failure, it's essential to understand that urea is produced in the liver as the end product of protein metabolism and is excreted by the kidneys. The exact identity and relative importance of all uremic toxics are unknown, and despite many decades of research, no single substance or group of substances have been directly related to adverse effects 1.

Key Points to Consider

• Urea levels are difficult to interpret as both high and low levels may indicate poor outcome, and the rates of change of urea levels may better reflect severity of renal failure 1.
• The use of blood solute concentrations to assess clearance must consider solute generation rates, and marker clearance should be used as the primary basis for CRRT dosing 1.
• Treatment dose affects outcome for stable patients with end-stage renal disease (ESRD), and recent evidence supports a similar relationship for patients with ARF, with a minimum Kt/V of 1.2 recommended to be delivered three times a week to patients with ARF 1.
• Higher doses of dialysis may be beneficial in critically ill patients with ARF based on studies in CRRT, with an intensity of continuous venovenous hemofiltration (CVVH) of 35 mL/kg/hour associated with improved survival compared to 20 mL/kg/hour in critically ill patients with ARF 1.

Clinical Implications

• In clinical practice, urea levels should be monitored and interpreted in the context of the patient's overall clinical condition, including symptoms, physical examination findings, and other laboratory results.
• The rates of change of urea levels, rather than absolute levels, should be used to assess the severity of renal failure and guide treatment decisions.
• Treatment doses for patients with ARF should be individualized based on the patient's clinical condition and response to treatment, with a minimum Kt/V of 1.2 recommended to be delivered three times a week.

From the Research

Urea Overview

• Urea is generated by the urea cycle enzymes, which are mainly in the liver but are also ubiquitously expressed at low levels in other tissues 2.
• The metabolic process is altered in several conditions such as by diets, hormones, and diseases 2.
• Urea is then eliminated through fluids, especially urine, and blood urea nitrogen (BUN) has been utilized to evaluate renal function for decades 2.

Clinical Applications of Urea

• Urea is a potent emollient and keratolytic agent, making it an effective monotherapy for conditions associated with dry and scaly skin 3.
• Effective treatment with urea has been reported for the following conditions: ichthyosis, xerosis, atopic dermatitis/eczema, contact dermatitis, radiation induced dermatitis, psoriasis/seborrheic dermatitis, onychomycosis, tinea pedis, keratosis, pruritus, and dystrophic nails 3.
• Urea has been used with other medications as a penetration enhancing agent, and it is a safe and tolerable topical drug without systemic toxicity 3.

Urea and Kidney Disease

• Urea is a marker of uraemic retention in chronic kidney disease (CKD) and of adequacy of intradialytic solute removal 4.
• Recent experimental data suggest that urea is toxic at concentrations representative for CKD, and it induces molecular changes related to insulin resistance, free radical production, apoptosis, and disruption of the protective intestinal barrier 4.
• Urea is at the origin of the generation of cyanate, ammonia, and carbamylated compounds, which have been linked to biological changes and are associated with cardiovascular and overall morbidity and mortality 4.

Urea at High Concentration on Skin and Annexes

• Clinical evidences of urea at high concentration indicate its important role in the presence of hyperkeratosis, and it has antiproliferative, keratolytic, moisturizing, and emollient properties 5.
• The keratolytic effect of urea is well-tolerated and virtually free from side effects, and compliance with topical therapy is directly related to the aesthetic and sensory acceptability of a topical agent 5.