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Chemistry

Clearances

Clearance tests assess the rate at which substances are removed from the body, usually by the kidneys. They are essential for evaluating kidney function

  • Key Concepts: Glomerular Filtration, Tubular Reabsorption, Tubular Secretion

  • Calculations: Clearance is calculated using the following formula:

    • C = (U x V) / P

      • C = Clearance (mL/min)
      • U = Urine concentration of the substance (mg/dL)
      • V = Urine flow rate (mL/min)
      • P = Plasma concentration of the substance (mg/dL)

Creatinine Clearance

  • Principle: Measures the rate at which creatinine is removed from the blood by the kidneys. Creatinine is a waste product of muscle metabolism that is freely filtered by the glomeruli and is neither reabsorbed nor significantly secreted by the tubules
  • Procedure
    1. 24-Hour Urine Collection: The patient collects all urine for a 24-hour period, starting and ending at the same time of day. The total volume of urine is measured, and a small aliquot is sent to the laboratory
    2. Blood Sample Collection: A blood sample is collected during the 24-hour urine collection period
    3. Creatinine Measurement: Creatinine is measured in both the urine and serum samples using the Jaffe reaction or an enzymatic method
    4. Calculation: Creatinine clearance is calculated using the formula:
      • C = (U x V) / P
  • Corrections: Corrected for Body Surface Area (BSA)
  • Reportable Range: 25 - 250 mL/min
  • Sources of Error * Incomplete Urine Collection: A major source of error. Ensure the patient understands the importance of collecting all urine during the 24-hour period * Improper Timing: Starting and ending the collection at the wrong time * Medications: Some medications can affect creatinine clearance * Muscle Mass: Creatinine production is related to muscle mass. Individuals with very high or low muscle mass may have inaccurate creatinine clearance estimates
  • Alternate Estimates (eGFR)
    • Equations
      • Cockcroft-Gault Equation: Estimates creatinine clearance based on serum creatinine, age, weight, and sex. Overestimates GFR in obese patients
      • MDRD (Modification of Diet in Renal Disease) Equation: Estimates GFR based on serum creatinine, age, sex, and ethnicity
      • CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equation: More accurate than MDRD, particularly at higher GFR levels
  • Clinical Significance
    • Creatinine clearance is a measure of glomerular filtration rate (GFR) and is used to assess kidney function
    • Decreased creatinine clearance indicates impaired kidney function
    • Creatinine clearance is used to stage chronic kidney disease (CKD) and to adjust medication dosages
  • CKD Stages * Stage 1: Kidney damage with normal or increased GFR (≥ 90 mL/min/1.73 m2) * Stage 2: Kidney damage with mild decrease in GFR (60-89 mL/min/1.73 m2) * Stage 3a: Moderate decrease in GFR (45-59 mL/min/1.73 m2) * Stage 3b: Moderate decrease in GFR (30-44 mL/min/1.73 m2) * Stage 4: Severe decrease in GFR (15-29 mL/min/1.73 m2) * Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m2 or dialysis)

Urea Clearance

  • Principle: Measures the rate at which urea is removed from the blood by the kidneys. Urea is freely filtered by the glomeruli and is partially reabsorbed by the tubules
  • Procedure
    1. Timed Urine Collection: The patient collects urine for a timed period (e.g., 1 hour, 2 hours). The total volume of urine is measured, and a small aliquot is sent to the laboratory
    2. Blood Sample Collection: A blood sample is collected during the urine collection period
    3. Urea Measurement: Urea is measured in both the urine and serum samples using the urease method
    4. Calculation: Urea clearance is calculated using the formula:
      • C = (U x V) / P
  • Clinical Significance
    • Urea clearance is a measure of kidney function and can be used to assess GFR
    • Urea clearance is less accurate than creatinine clearance because urea reabsorption varies with urine flow rate and hydration status
    • Urea clearance is primarily of historical interest and is not commonly used in clinical practice

Key Terms

  • Clearance: The rate at which a substance is removed from the blood by the kidneys
  • Glomerular Filtration Rate (GFR): The rate at which blood is filtered by the glomeruli
  • Tubular Reabsorption: The process by which substances are reabsorbed from the renal tubules back into the bloodstream
  • Tubular Secretion: The process by which substances are secreted from the bloodstream into the renal tubules
  • Creatinine: A waste product of muscle metabolism
  • Urea: A waste product of protein metabolism
  • 24-Hour Urine Collection: A collection of all urine produced over a 24-hour period
  • Timed Urine Collection: A collection of urine produced over a specified period of time
  • Jaffe Reaction: A chemical reaction used to measure creatinine
  • Urease Method: An enzymatic method used to measure urea
  • Estimated Glomerular Filtration Rate (eGFR): An estimate of GFR based on serum creatinine, age, sex, and ethnicity
  • Body Surface Area (BSA): The measured or calculated surface of a human body
  • CKD Stages: Stages of chronic kidney disease based on GFR