Creatinine Clearance

Aka: Creatinine Clearance, Glomerular Filtration Rate, GFR, CrCl, Cockcroft-Gault, Modification of Diet in Renal Disease, MDRD, Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI

1. See Also
   1. Serum Creatinine
   2. Serum Cystatin C
   3. Chronic Kidney Disease
2. Indications
   1. Creatinine Clearance estimates Glomerular Filtration Rate (GFR)
3. Interpretation: Normal Creatinine Clearance
   1. Men
      1. Average: 120 ml/min/1.73 m2 (+/-25) or 175 Liters/day
      2. Range: 97-137 ml/min/1.73 m2 (0.93-1.32 ml/sec/m2 IU)
   2. Women
      1. Average: 95 ml/min/1.73 m2 (+/-20) or 135 Liters/day
      2. Range: 88-128 ml/min/1.73 m2 (0.85-1.23 ml/sec/m2 IU)
4. Calculation: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
   1. Calculation
      1. Males: 141 * min (sCr/0.9 or 1) ^ -0.411 * max(sCr/0.9 or 1)^ - 1.209 * 0.993 ^ ageY
      2. Females: 141 * min (sCr/0.7 or 1) ^ -0.329 * max(sCr/0.7 or 1)^ - 1.209 * 0.993 ^ ageY * 1.018
      3. Black: Multiply above equation (based on gender) by 1.159
   2. Annotation
      1. Where sCr is Serum Creatinine
      2. Min is the minimum value (either that calculated or 1)
      3. Max is the maximum value (either that calculated or 1)
      4. Where ^ represents to the power of...
   3. Efficacy
      1. More accurate than either CKD or MDRD
   4. Alternatives
      1. GFR may also be estimated from Serum Cystatin C instead of Serum Creatinine
         1. Consider if abnormal GFR based on Creatinine Clearance suspected to be False Positive
   5. Resources
      1. National Kidney Foundation
         1. https://www.kidney.org/professionals/kdoqi/gfr_calculator
   6. References
      1. Levey (2009) Ann Intern Med 150(9): 604-12 [PubMed]
5. Calculation: Cockcroft-Gault formula for GFR estimate
   1. Indications: Stable Kidney Function
      1. As of 2017, primarily used only for medication Renal Dosing (other calculations are preferred)
      2. Older patients
      3. General screening
   2. Male GFR = (140 - age) x (weight) / (sCr x 72)
   3. Female GFR = (140 - age) x (weight) x 0.85 / (sCr x 72)
   4. Annotation
      1. Where GFR is Glomerular Filtration Rate in ml/min
      2. Where age is in years
      3. Where weight is Lean Body Mass in kilograms
      4. Where sCr is Serum Creatinine in mg/dl
   5. Efficacy
      1. As accurate as 24 hour urine in most cases
      2. Exceptions: See 24 hour CrCl indications below
   6. Resources: GFR Calculator
      1. http://www.kidney.org/kls/professionals/
6. Calculation: Abbreviated MDRD Study Equation
   1. Indications: Chronic Kidney Disease, stable function
      1. Middle aged patients
      2. Black patients
      3. Diabetic Nephropathy
      4. Status-post Kidney transplant
   2. Efficacy
      1. More accurate than Cockroft-Gault in CRF
         1. Levey (1999) Ann Intern Med 130:461-70 [PubMed]
      2. Overestimates Chronic Kidney Disease when used as a general screening tool
         1. Underestimates GFR in the absence of Kidney disease
         2. Rule (2004) Ann Intern Med 141:929-37 [PubMed]
   3. Formula: GFR = 186 x (sCr)^-1.154 x (age)^-0.203
      1. Where sCr is raised by power of -1.154
      2. Where age is raised by power of -0.203
   4. Modifiers
      1. Female: Multiply GFR by 0.742
      2. Black: Multiply GFR by 1.210
   5. Annotation
      1. Where GFR=Glomerular Filtration Rate ml/min/1.73 m2
      2. Where sCr is Serum Creatinine in mg/dl
7. Calculation: 24 hour Creatinine Clearance
   1. Previously considered gold standard GFR evaluation
      1. Now thought to be less accurate than calculations (see above) due to flawed collection
   2. Indications
      1. Pregnancy
      2. Severely underweight or Overweight
      3. Very young and very old
      4. Malnutrition
      5. Skeletal Muscle disorders, Paraplegia, Quadriplegia
   3. Formula
      1. CrCl = (uCr x uV) / (sCr x 1440)
   4. Annotation
      1. Where CrCl is Creatinine Clearance in ml/min
      2. Where uCr is Urine Creatinine in mg/dl
      3. Where sCr is Serum Creatinine in mg/dl
      4. Where uV is 24 hour Urine Volume in ml
      5. Where 1440 represents number of minutes in 24 hours
   5. Indications (where calculation above is inaccurate)
      1. Altered Protein intake
         1. Vegetarian diet
         2. Creatine Supplementation
      2. Altered Muscle mass
         1. Malnutrition or Muscle wasting
         2. Amputation
8. Interpretation: Increased GFR
   1. Pregnancy
   2. Exercise
9. Interpretation: Decreased GFR
   1. Chronic Kidney Disease or Renal Insufficiency
   2. Advanced age
      1. Normal GFR is 125 ml/min/1.73 m2 at age 30 years
      2. GFR decreases by 1 ml/min/year over age 30 years
   3. Inadequate urine specimen collection
      1. See Urine Creatinine for judging adequacy
   4. Medications (Decrease tubular secretion of Creatinine)
      1. Cimetidine
      2. Procainamide
      3. Antibiotics
      4. Quinidine
10. Precautions: Pitfalls
    1. Creatinine Clearance (CrCl) and estimated Glomerular Filtration Rate (eGFR) are NOT interchangeable
       1. Older dosing guidelines and precautions were given in CrCl, but newer guidelines refer to eGFR
          1. CrCl units are ml/min
          2. eGFR units are ml/min/1.73m^2
       2. Drug dosing guidelines are specific for their cutoff ranges
          1. Using eGFR when CrCl is indicated will miss dose adjustments in up to 50% of cases
          2. Highest risk for miscalculation is in the elderly and in moderate to severe Chronic Kidney Disease
    2. Calculating GFR in specific cohorts
       1. As of 2020, guidelines recommend calculating eGFR without regard to race
       2. Overweight (bodyweight >20-30% over Ideal Weight)
          1. Calculate based on adjusted body weight
          2. Adjusted body weight = wtKgIdeal + 0.4 * (wtKgActual - wtKgIdeal)
       3. Underweight
          1. Use actual weight
          2. Do not round up when calculating CrCl (significantly underestimates GFR)
       4. Alternative calculation for patients well above or below their Ideal Body Weight
          1. Corrected eGFR = eGFR * BSA/1.73 m2
       5. Elderly
          1. Do not round up when calculating CrCl (significantly underestimates GFR)
       6. Limb Amputation or Quadriplegic
          1. Measure 24 hour Creatinine Clearance
       7. Abnormal Creatinine Clearance suspected to be False Positive
          1. Serum Cystatin C may be used as alternative to Serum Creatinine
    3. Creatinine Clearance (by 24 hour urine) is overestimated at decreased GFR
       1. As GFR decreases, secreted Creatinine makes up larger percentage of total Urine Creatinine
       2. Consider pre-medicating the 24 hour Urine Collection
          1. Give Cimetidine or Trimethoprim for 2 days prior to 24 hour Urine Collection
          2. Overcomes the over-estimatation of GFR