Creatinine urine test

Creatinine and Creatine Metabolism

Creatinine is a waste product generated from the normal breakdown of muscle tissue. It is produced from creatine, a compound primarily found in muscle where its phosphorylated form, phosphocreatine, serves as a readily available energy reserve for muscle contraction.

Creatinine is produced at a relatively constant rate, proportional to the individual's muscle mass. It enters the bloodstream and is then filtered out by the kidneys to be excreted in the urine.

What is a Creatinine Urine Test?

A Creatinine Urine Test measures the amount of creatinine present in a urine sample. This can be done on a random urine sample or, more commonly, on a timed collection, usually over 24 hours.

Measuring urine creatinine is often done in conjunction with measuring creatinine levels in the blood (serum creatinine) to assess kidney function.

Why is Urine Creatinine Measured?

Measuring creatinine in urine serves several important clinical purposes:

• Assessing Kidney Filtration Function: Calculating Creatinine Clearance using both urine and serum creatinine levels provides an estimate of the Glomerular Filtration Rate (GFR), a key indicator of overall kidney function.
• Checking Adequacy of Timed Urine Collections: Measuring the total creatinine excreted in a 24-hour urine sample helps determine if the collection was complete, as daily creatinine excretion is relatively constant for an individual based on muscle mass.
• Normalizing Urine Analyte Concentrations: Measuring creatinine in a random urine sample allows for the calculation of ratios, such as the Albumin-to-Creatinine Ratio (ACR) or Protein-to-Creatinine Ratio (PCR). These ratios help correct for variations in urine concentration (hydration status) and provide a more accurate assessment of protein or albumin excretion, which are markers of kidney damage.
• Assessing Urine Concentrating Ability: The ratio of urine creatinine to serum creatinine (Concentration Index) can provide information about the kidney's ability to concentrate urine.

Creatinine Handling by the Kidneys

Creatinine is primarily removed from the body by the kidneys through two main processes:

• Glomerular Filtration: Creatinine is freely filtered from the blood into the primary urine by the glomeruli (the kidney's filtering units).
• Tubular Secretion: A smaller amount of creatinine is actively secreted directly into the urine by the renal tubules.

Unlike many other substances filtered by the glomeruli, creatinine is generally not significantly reabsorbed back into the bloodstream by the tubules (although minimal reabsorption might occur at very low urine flow rates).

Because it is filtered and minimally secreted/reabsorbed, the rate at which creatinine is cleared from the blood by the kidneys approximates the Glomerular Filtration Rate (GFR).

However, it's important to note that as kidney function declines (renal failure) and serum creatinine levels rise, the relative contribution of tubular secretion increases. This means that creatinine clearance can slightly overestimate the true GFR, especially in advanced kidney disease.

Creatinine Clearance and GFR

Creatinine Clearance (CrCl) measures the volume of blood plasma that is cleared of creatinine per unit time (usually mL/min). It is calculated using the concentration of creatinine in a timed urine sample (usually 24 hours), the volume of urine produced during that time, and the concentration of creatinine in the blood (serum).

The formula is generally: CrCl (mL/min) = [Urine Creatinine (mg/dL) * Urine Volume (mL)] / [Serum Creatinine (mg/dL) * Time (min)]

Creatinine clearance is used to estimate the Glomerular Filtration Rate (GFR), which reflects the total filtration capacity of the kidneys and is a primary measure of kidney health. In healthy individuals, GFR typically ranges from about 90 to 120 mL/min/1.73m², varying with age, sex, and body size. Values below 60 mL/min/1.73m² for three months or more indicate chronic kidney disease.

Measuring creatinine clearance using a 24-hour urine collection was historically common but is cumbersome and prone to collection errors. Today, GFR is more often estimated (eGFR) using formulas (like CKD-EPI or MDRD) that incorporate serum creatinine, age, sex, and sometimes race, without requiring a urine collection.

Urine Concentration Index (CI)

The ratio of the concentration of creatinine in urine to its concentration in blood plasma is known as the Concentration Index (CI). It reflects the kidney's ability to concentrate urine by reabsorbing water.

The formula is:

CI = U / P, where
U = Urine Creatinine concentration
P = Plasma (Serum) Creatinine concentration

In healthy individuals with normal concentrating ability, the CI value is typically greater than 60.

Tubular Reabsorption Calculation

The percentage of the glomerular filtrate that is reabsorbed by the tubules can be estimated using GFR (approximated by CrCl) and the urine flow rate (minute diuresis).

The formula is:

R% = [(F - V) / F] * 100, where
F = Glomerular Filtration Rate (mL/min) (e.g., estimated by CrCl)
V = Minute Urine Volume (mL/min)

Normally, the kidneys reabsorb a very large percentage of the filtered fluid, typically greater than 97%.

Factors Affecting Creatinine Levels

• Muscle Mass: Higher muscle mass leads to higher creatinine production and excretion.
• Diet: High intake of cooked meat can temporarily increase creatinine levels.
• Kidney Function: Reduced GFR leads to increased serum creatinine and potentially decreased urine creatinine excretion over time. Tubular damage can increase urine creatinine excretion relative to filtration.
• Hydration Status: Affects urine concentration but generally not the total amount excreted over 24 hours. Affects random urine creatinine concentration significantly.
• Medications: Some drugs (e.g., cimetidine, trimethoprim) can interfere with tubular secretion, increasing serum creatinine without changing GFR. Others can be nephrotoxic.
• Age: GFR naturally declines with age.
• Intense Exercise: Can temporarily increase creatinine levels.
• Sodium/Potassium Intake: Dietary deficiencies might potentially influence clearance calculations.

Creatinuria (Creatine in Urine)

While creatinine is normally excreted, creatine itself is typically absent or present in very small amounts in adult urine because it is effectively utilized by muscles or converted to creatinine.

However, detectable creatine in the urine (creatinuria) can occur physiologically:

• Puberty: Especially during periods of rapid muscle growth (around 14-16 years), active creatine synthesis may exceed muscle uptake, leading to excretion.
• Pregnancy: Hormonal changes and increased demands can lead to creatinuria.
• Elderly: Muscle atrophy can lead to incomplete utilization of synthesized creatine.

Creatinuria can also occur pathologically:

• Muscle Diseases: Conditions involving muscle breakdown or atrophy (e.g., muscular dystrophies, myositis) release creatine.
• Starvation/Malnutrition: Particularly carbohydrate starvation, where muscle protein may be broken down.
• Hyperthyroidism: Increased metabolic rate can affect creatine metabolism.
• Certain Infections/Fever: Increased catabolism.
• Diabetes Mellitus: Especially if poorly controlled.

Creatine may also appear in the urine of healthy individuals after very strenuous physical exertion.

Disorders Affecting Creatine/Creatinine Metabolism

Conditions that disrupt the normal metabolism or handling of creatine and creatinine include:

• Kidney Disease: Affects filtration, secretion, and potentially reabsorption, altering both serum and urine creatinine levels and clearance.
• Liver Disease: Since creatine is synthesized partly in the liver, severe liver disease could potentially impact creatine production, although kidney function usually dominates creatinine level changes.
• Muscle Diseases: Myopathies, muscular dystrophies, rhabdomyolysis (acute muscle breakdown), and significant muscle atrophy affect creatine release and creatinine production.
• Endocrine Disorders: Such as diabetes mellitus and hyperthyroidism.
• Radiation Sickness: Can cause tissue damage, including muscle.
• Infections: Severe infections can increase muscle breakdown.

A decrease in urine creatinine excretion (compared to expected levels based on muscle mass) can occur in conditions where the conversion of creatine to creatinine is impaired or where kidney function is severely reduced.

The Urine Creatinine Test Procedure

• Sample Type: Can be a random ("spot") urine sample or a timed collection (most commonly 24 hours).
• Random Sample: Often used for calculating ratios (ACR, PCR). Requires a clean-catch midstream urine sample.
• 24-Hour Collection: Requires collecting *all* urine produced over a full 24-hour period in a special container provided by the lab (may contain a preservative). Precise timing and complete collection are essential for accurate creatinine clearance calculations. Specific instructions are provided by the healthcare provider or lab.
• Preparation: Generally no special preparation like fasting is needed, but vigorous exercise should be avoided before and during a 24-hour collection. Stay normally hydrated unless instructed otherwise. Inform your doctor about all medications.
• Analysis: The concentration of creatinine in the urine sample is measured in the laboratory.

References

1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (n.d.). Creatinine Test. NIH. Retrieved from https://www.niddk.nih.gov/health-information/diagnostic-tests/creatinine-test
2. Lab Tests Online. (n.d.). Creatinine. Retrieved from https://labtestsonline.org/tests/creatinine
3. Mayo Clinic Staff. (n.d.). Creatinine test. Mayo Clinic Patient Care & Health Information. Retrieved from https://www.mayoclinic.org/tests-procedures/creatinine-test/about/pac-20384646
4. Levey, A. S., Stevens, L. A., Schmid, C. H., Zhang, Y. L., Castro, A. F., Feldman, H. I., ... & CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). (2009). A new equation to estimate glomerular filtration rate. *Annals of Internal Medicine*, 150(9), 604–612. (Reference for eGFR calculation method)
5. Perrone, R. D., Madias, N. E., & Levey, A. S. (1992). Serum creatinine as an index of renal function: new insights into old concepts. *Clinical Chemistry*, 38(10), 1933–1953.