From the Guidelines
Elevated urea levels in the blood primarily result from decreased kidney function, where the kidneys fail to adequately filter waste products, and can be caused by various factors including acute kidney injury, chronic kidney disease, and end-stage renal disease. The development of renal impairment is associated with risk factors including age, hypertension, dyslipidaemia, and the metabolic syndrome, which are also cardiovascular disease risk factors 1. Dehydration significantly contributes to urea elevation by reducing blood flow to the kidneys, concentrating waste products in the bloodstream. High-protein diets increase urea production as protein metabolism generates more nitrogenous waste. Certain medications, including NSAIDs (ibuprofen, naproxen), some antibiotics (aminoglycosides), and diuretics can impair kidney function or alter urea excretion 1. Gastrointestinal bleeding can raise urea levels as blood proteins are broken down in the gut. Other contributing factors include severe heart failure (reducing kidney perfusion), excessive tissue breakdown (as in burns or trauma), and certain metabolic disorders.
Causes of Urea Rise
- Acute kidney injury
- Chronic kidney disease
- End-stage renal disease
- Dehydration
- High-protein diets
- Certain medications (NSAIDs, some antibiotics, diuretics)
- Gastrointestinal bleeding
- Severe heart failure
- Excessive tissue breakdown
- Certain metabolic disorders
Management typically involves treating the underlying cause, ensuring adequate hydration, temporarily reducing protein intake, adjusting medications, and in severe cases, dialysis may be necessary to remove excess urea from the bloodstream. The estimation of total body water by any formulae has not been validated in children with renal failure, and the use of Kt/Vurea as an indication for the initiation of dialysis is recommended considering this caveat 1. It is essential to monitor progression of kidney failure by following total weekly renal urea nitrogen clearance (Kt urea) normalized to urea volume of distribution (V), and to initiate dialysis when the weekly renal Kt/Vurea falls below 2.0.
From the Research
Causes of Urea Rise
- 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, which can lead to an increase in urea levels 2.
- Certain medications, such as renin-angiotensin-aldosterone-system (RAAS) inhibitors, diuretics, or non-steroidal-anti-inflammatory drugs (NSAIDs), can also contribute to an increase in urea levels, especially in patients with chronic kidney disease (CKD) or heart failure 3.
- Urea itself can be toxic at high concentrations, leading to molecular changes related to insulin resistance, free radical production, apoptosis, and disruption of the protective intestinal barrier 4.
- Dehydration, vomiting, diarrhea, fever, chills, or gastrointestinal infection can also cause a rise in urea levels due to decreased fluid volume and renal function 3.
Related Conditions
- Chronic kidney disease (CKD) is a condition where the kidneys are damaged and cannot filter waste products, such as urea, effectively, leading to a buildup of toxins in the body 4.
- Heart failure can also lead to increased urea levels due to decreased renal function and fluid overload 5, 6.
- Age, particularly being 70 years or older, is also a risk factor for increased urea levels due to decreased renal function and other comorbidities 3, 5.