From the Guidelines
Urea levels should not be used in isolation to diagnose or manage uremia, as they do not directly correlate with adverse effects, and instead, the rates of change of urea levels over time should be considered to reflect the severity of renal failure. When interpreting urea levels, it is essential to consider the clinical context and the rates of change over time, as both high and low levels can indicate poor outcomes 1. The use of urea as a marker substance for uremia is limited, and other factors such as solute generation rates and clearance should be taken into account 1.
Key Considerations
- Urea is only a marker substance for the clinical condition known as uremia, and its levels should not be used in isolation to diagnose or manage the condition 1.
- The rates of change of urea levels over time are a better indicator of the severity of renal failure than absolute levels 1.
- Clearance of various marker substances, including urea, is a more accurate measure of therapy dose than blood solute concentrations alone 1.
- The use of standardized Kt/V or equivalent renal clearance is recommended to compare disparate therapies and different frequencies of treatment 1.
Clinical Implications
- In patients with acute renal failure (ARF), a minimum Kt/V of 1.2 should be delivered three times a week, and higher doses of dialysis may be beneficial in critically ill patients 1.
- The intensity of continuous venovenous hemofiltration (CVVH) of 35 mL/kg/hour is associated with improved survival compared to 20 mL/kg/hour in critically ill patients with ARF 1.
- A dose-response relationship exists for dialysis in ARF, and the traditional, ESRD-based, dose recommendation may be too low 1.
From the Research
Urena Research
- Urea has been traditionally considered biologically inert, but recent studies suggest it may be toxic at concentrations representative of chronic kidney disease (CKD) 2.
- Urea can induce molecular changes related to insulin resistance, free radical production, apoptosis, and disruption of the protective intestinal barrier 2.
- Urea is also 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 2.
Urea Cycle Disorders
- Urea cycle disorders (UCDs) are a group of genetic disorders that can cause hyperammonemia, leading to intellectual disability or death 3.
- Effective therapies for UCDs exist, but under-recognition and delayed diagnosis are still widespread 3.
- Revised guidelines for the diagnosis and management of UCDs have been published, providing a trans-European consensus based on robust evidence and involving professionals from nine countries 3.
Key Findings
- The kinetics of urea may not be representative of the kinetics of other uraemic retention solutes, and urea may not be responsible for all complex metabolic and clinical changes in CKD 2.
- Future efforts to improve outcomes for patients with CKD may focus on improving removal of solutes implied in the uraemic syndrome, including urea, and taking into account the impact of the intestine and residual renal function on solute concentration 2.