Creatinine with Estimated Glomerular Filtration Rate (eGFR)

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Subject: Creatinine with Estimated Glomerular Filtration Rate (eGFR)

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Definition

  • Creatinine is formed by the hydrolysis of creatine and phosphocreatine in muscle and by ingestion of meat. It is freely filtered at the glomerulus and secreted at the proximal tubule; some is resorbed. GFR is equal to the total of the filtration rates of the functioning nephrons in the kidney.

  • Normal range:

    • Creatinine

      • 0–1 month: 0.00–1.00 mg/dL

      • 1 month–1 year: 0.10–0.80 mg/dL

      • 1–16 years: 0.20–1.00 mg/dL

      • >16 years, female: 0.50–1.20 mg/dL

      • >16 years, male: 0.60–1.30 mg/dL

    • eGFR

      • >16 years: >60 mL/minute/1.73 m2

      • Three equations are currently used for the calculation of GFR:

        • IDMS-Traceable MDRD Study Equation for the calculation of GFR:

          • GFR (mL/minute/1.73 m2) = 175 × (Scr)−1.154 × (age)−0.203 × (0.742 if female) × (1.212 if African American) (conventional units); where Scr is serum creatinine.

          • (The equation has not been validated in children and will only be reported for patients >16 years of age. The equation is normalized for an average adult body surface area of 1.73 m2; weight and height adjustment is not necessary.)

        • Cockcroft-Gault formula

          • CrCl = {((140 − age) × weight)/(72 SCr)} × 0.85 if female

          • Where CrCl is expressed in milliliters per minute, age in years, weight in kilograms, and serum creatinine (SCr) in milligrams per deciliter.

        • The chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation is based on the same four variables as the modification of diet in renal disease (MDRD) Study equation, but uses a two-slope spline to model the relationship between estimated GFR and serum creatinine, and a different relationship for age, sex, and race. The equation was reported to perform better and with less bias than the MDRD Study equation, especially in patients with higher GFR. This results in reduced misclassification of CKD.

          • GFR = 141 × min(Scr/κ,1)α × max(Scr/κ,1) − 1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black]

          • Where Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is −0.329 for females and −0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1.

Use

  • To diagnose renal insufficiency; more specific and sensitive indicator of renal disease than of BUN. Use of simultaneous BUN and creatinine determinations provides more information in conditions.

  • Adjusting dosage of renally excreted medications.

  • Monitoring renal transplant recipients.

  • Serum creatinine levels are a proxy for reduced skeletal muscle mass.

  • eGFR: Serum creatinine measurement is used in estimating GFR for people with CKD and those with risk factors for CKD (DM, hypertension, cardiovascular disease, and family history of kidney disease).

Interpretation

Increased In

  • Diet: ingestion of creatinine (roast meat).

  • Muscle disease: gigantism, acromegaly.

  • Pre- and postrenal azotemia.

  • Impaired kidney function; 50% loss of renal function is needed to increase serum creatinine from 1.0 to 2.0 mg/dL. Therefore, the test is not sensitive for mild to moderate renal injury.

  • An increase in serum creatinine occurs in 10–20% of patients taking aminoglycosides and ≤20% of patients taking penicillins (especially methicillin).

Decreased In

  • Pregnancy: Normal value is 0.4–0.6 mg/dL. A value >0.8 mg/dL is abnormal and should alert the clinician to further diagnostic evaluation.

  • Creatinine secretion is inhibited by certain drugs (e.g., cimetidine, trimethoprim).

  • Proxy for reduced skeletal muscle mass.

Limitations

  • Artifactual decrease by:

    • Marked increase of serum bilirubin

    • Enzymatic reaction (glucose >100 mg/dL)

  • Artifactual increase due to

    • Reduction of alkaline picrate (e.g., glucose, ascorbate, uric acid). Ketoacidosis may substantially increase serum creatinine results with alkaline picrate reaction.

    • Formation of colored complexes (e.g., acetoacetate, pyruvate, other ketoacids, certain cephalosporins).

    • Enzymatic reaction: 5-Fluorocytosine may increase serum creatinine ≤0.6 mg/dL.

    • Other methodologic interference (e.g., ascorbic acid, phenolsulfonphthalein, l-dopa).

    • Some medications inhibit tubular secretion of creatinine, thereby decreasing creatinine clearance and increasing serum creatinine without a change in GFR. These medications include the following:

    • The Cockcroft-Gault equation estimates creatinine clearance and is not adjusted for body surface area. The CKD-EPI and MDRD Study equations estimate GFR adjusted for body surface area. GFR estimates from the CKD-EPI and MDRD Study equations can therefore be applied to determine level of kidney function, regardless of a patient's size. In contrast, estimates based on the Cockcroft-Gault equation can be used for drug dosage recommendations, whereas GFR estimates based on the MDRD Study should be “unadjusted” for body surface area.

    • The Cockcroft-Gault equation appears to be less accurate than the MDRD Study equation, specifically in older and obese people.

    • Modifications of the CKD-EPI and MDRD Study equations have been developed for Japanese and Chinese people. They have not yet been validated for Japanese or Chinese people living in other countries, including the United States. Studies in other ethnic groups have not yet been performed.

 
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