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Preface:
Continuing the discussion on indicators reflecting kidney function, today we will talk about the two most familiar indicators — Urea / Creatinine (UREA/CREA), and see if there is anything new.
PART01 : What are UREA and CREA?
★Urea (UREA/BUN): It is the main end product of protein metabolism in the human body. Amino acids undergo deamination producing NH3 and CO2, which are synthesized into urea in the liver. Each gram of protein metabolized produces 0.3g of urea. The nitrogen content in urea is 28/60, almost half. Usually, the kidney is the main organ for excreting urea. After being filtered by the glomerulus, urea can be reabsorbed in various segments of the tubules, but the faster the urine flow in the renal tubules, the less absorption occurs, reaching a maximum clearance rate. Like blood creatinine, in the early stage of kidney impairment, blood urea nitrogen (BUN) can remain within the normal range. When the glomerular filtration rate decreases to less than 50% of normal, the concentration of blood urea nitrogen rises rapidly.
★Creatinine (CREA): It is a product of muscle metabolism in the body, where every 20g of muscle metabolized produces 1mg of creatinine. Creatinine is mainly excreted through glomerular filtration by the kidneys. Blood creatinine comes from both exogenous and endogenous sources, where exogenous creatinine arises from the metabolism of meat in the diet; endogenous creatinine comes from muscle tissue metabolism. When meat intake is stable and muscle metabolism has no major changes, creatinine production remains relatively constant.
★Clinical reference values for UREA: 3.0/7.1/14.2; for CREA: 40/141/530.
PART02 : Clinical applications of UREA/CREA — Physiological variations?
★UREA: It is a product of protein metabolism. In cases of low protein intake, patients who eat predominantly vegetarian diets or less meat will show low UREA. Those who are lean or pregnant may also show reduced urea levels.
★CREA: Creatinine is a muscle metabolism product. For people with developed muscles, intense exercise can lead to significant muscle breakdown, causing transient increases in blood creatinine. However, urine protein quantification, routine urine tests, and other indicators remain normal. This type of blood creatinine elevation is physiological and usually subsides naturally. In addition, consuming large amounts of meat or protein within a short time can also cause a small rise in creatinine, peaking around 2-4 hours, which is also a physiological increase.
★Special populations to note: For example, children who grow rapidly and are very active have relatively higher CREA, while elderly people with reduced muscle mass show lower CREA. During pregnancy, creatinine tends to be lower than in normal individuals because although creatinine production remains unchanged, plasma volume increases and dilutes the blood. Patients with malnutrition often have lower muscle mass, leading to decreased CREA.
PART03: Clinical applications of UREA — Elevated levels
★Prerenal disease: The most important cause is dehydration, which leads to blood concentration, reduced renal blood flow, decreased glomerular filtration rate, and urea retention in the blood. Common in severe vomiting, pyloric obstruction, intestinal obstruction, and chronic diarrhea.
★Renal disease: Acute glomerulonephritis, late-stage nephropathy, renal failure, chronic pyelonephritis, and toxic nephritis can cause elevated urea levels in the blood.
★Postrenal disease: Conditions such as prostate enlargement, urinary tract stones, urethral stricture, and bladder tumors can compress the urinary tract causing obstruction and increasing blood urea levels.
▼Note: Only in renal diseases does creatinine concurrently increase in a proportionate manner. In prerenal and postrenal diseases, urea elevation is more pronounced, whereas creatinine increase is less obvious and disproportionately low.
PART04: Clinical applications of UREA — Decreased levels
UREA is a protein metabolism product. When intake is insufficient or there is excessive loss, UREA levels decrease.
★Renal dysfunction: Low blood urea nitrogen may be related to low protein intake, pregnancy, or liver failure.
★Liver failure: The liver is a vital metabolic organ. Liver failure leads to poor nutrient absorption. Another reason is inadequate protein intake by the patient, combined with large consumption due to abnormal liver function.
PART05: Clinical applications of CREA — Elevated levels
Generally, increased CREA indicates abnormal kidney function. When glomerular filtration function declines to a certain extent, CREA rises.
★Acute and chronic glomerulonephritis and other diseases causing decreased glomerular filtration: Blood creatinine can increase. Note that creatinine only changes noticeably when GFR drops near 50%. Therefore, for early kidney damage, other indicators (e.g., urine microalbumin, Cystatin C, β2-microglobulin, retinol, urine protein electrophoresis, etc.) need to be jointly analyzed.
★Acute kidney injury: A sudden decline in kidney function leading to retention of urea and other nitrogenous wastes, as well as extracellular fluid and electrolyte imbalances. Defined as an increase in CREA by ≥0.3 mg/dL (≥26.5 μmol/L) within 48 hours, or CREA rising to ≥1.5 times baseline within the previous 7 days, or urine output <0.5 ml/kg/hr lasting 6 hours.
★Fulminant myocarditis: Patients commonly suffer multi-organ failure, mainly affecting heart, kidneys, and liver. Studies show significant increases in CREA, ALT, and CK-MB in these patients. CREA elevation here is accumulated from kidney involvement and requires comprehensive assessment.
★Muscle injury: Can cause rhabdomyolysis, releasing large amounts of myoglobin. Myoglobin loosely binds plasma α2-globulin, is easily filtered by glomeruli, and appears in urine. It can cause renal vasoconstriction, tubular obstruction, and directly impair tubular transport, resulting in kidney injury and elevated blood creatinine.
★Anemia: A major complication of chronic kidney disease and a risk factor for cardiovascular events and poor quality of life. Studies show diabetic nephropathy patients with anemia have significantly higher blood creatinine than those without anemia.
▼Do not rely solely on CREA results, but consider other kidney-related indicators jointly, along with other tests (ultrasound, radiology, biopsy pathology, etc.) for comprehensive assessment. No single indicator alone has “absolute” diagnostic significance. Always remember to analyze comprehensively and diagnose collaboratively.
PART06: Clinical applications of CREA — Decreased levels
CREA is a muscle metabolism product. Most causes of decreased CREA are physiological. Generally, CREA decrease is found in progressive muscle atrophy, leukemia, anemia, liver dysfunction, and pregnancy. When CREA is low, it is necessary to distinguish true underlying disease (analyzing any biochemical indicator requires considering three steps: where does the substance come from? where does it go? how is it transformed? Understanding these clarifies the theoretical basis for changes, and then one deduces from there).
PART07: Clinical applications of UREA/CREA — Urea to Creatinine ratio
The ratio helps better identify causes of acute kidney injury, normally (10-20):1. When the ratio > 20, it is common in prerenal acute kidney injury, causing slowed urine production and increased tubular urea reabsorption, leading to elevated urea. Also, patients with azotemia or negative nitrogen balance show elevated BUN/creatinine ratio, and gastrointestinal bleeding can also raise blood urea nitrogen. A ratio <10 is often seen in patients with protein malnutrition; such patients should increase protein intake to restore the ratio.
▼Note: Previously, urea nitrogen and creatinine were reported in mg/dL units; now many labs use mmol/L or μmol/L, so multiply by ×250 when calculating this ratio.
PART08: Are Urea (UREA) and Blood Urea Nitrogen (BUN) the same test?
Theoretically, they are not the same test, but many labs have conflated them (mainly due to traditional practices), essentially treating them as equivalent. In fact, urea is directly measured, while BUN measures the nitrogen in urea. One urea molecule contains two nitrogen atoms, so the molar concentration of urea differs by a factor of two from BUN. The conversion formulas are: Urea (mg/dL) × 0.1665 = Urea (mmol/L); Urea (mg/dL) × 0.466 = BUN (mg/dL); BUN (mg/dL) × 2.144 = Urea (mg/dL) (Note: this BUN is true blood urea nitrogen, not the BUN in current report forms). Therefore, in practice, UREA and BUN basically mean the same thing.
PART09: Clinical applications of UREA/CREA — Non-laboratory influencing factors
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PART10: Clinical applications of UREA/CREA — Interpretations in package inserts
Carefully read the package insert. A good one is your best and easiest teacher to acquire knowledge. The following inserts come from Roche Diagnostics.
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Sinan says:
There is actually little to say about UREA/CREA because they are quite familiar. Just a reminder to make comprehensive judgments: never diagnose a disease from a single abnormal result, nor declare absence of disease with a normal result. Analyze comprehensively and judge jointly. As the old saying goes, “Test to seek truth, verify to uphold integrity!”
Note: Due to limited knowledge and experience, this article mainly compiles past data and practical experience, for communication, learning, and sharing only. It is not intended as clinical diagnostic or treatment advice. Please contact the author privately for corrections. Non-commercial use only, for professional reference and exchange. Please contact the author for deletion if copyright is infringed. Thank you!
Hayao Miyazaki:
There is always a period in life full of uncertainty, but besides facing it bravely, we have no other choice.