Creatinine Clearance

The definition and staging of chronic kidney disease depends on the assessment of glomerular filtration rate (GFR). The most widely used measures of GFR in clinical practice are the serum creatinine concentration and the 24-hour creatinine clearance (CCr) calculation.  

The diagnostic usefulness of serum creatinine as an indicator of glomerular filtration rate (GFR) is based upon its constant production from muscle creatine and its relatively constant renal excretion rate. About 1 to 2% of the creatine in muscle is converted to creatinine daily. The amount of creatinine formed is proportional to muscle mass, resulting in differences in serum creatinine concentration related to age, gender, and race. Serum creatinine is decreased in individuals with small stature, cachexia, amputations, muscle disease or vegetarian diets.  Advanced liver disease causes low serum creatinine because of decreased hepatic conversion of creatine to creatinine. 

Serum creatinine is a relatively insensitive indicator of renal disease. A change in serum creatinine from 0.6 -1.2 mg/dL reflects a 50% decline in GFR, even though creatinine is still within the normal range.  If a previous baseline creatinine is not available for comparison, a serum creatinine level of 1.2 mg/dL might be considered clinically insignificant.  

Calculating the clearance of endogenous creatinine is the most practical test of renal function. Urine is collected for 24 hours and a blood sample is collected during this collection interval. Serum and urine creatinine levels are measured and the creatinine clearance calculated using the following formula: 

Urine creatinine x urine volume = mL 

Serum creatinine x min of duration = min 

This value is then corrected for body surface area: 

Creatinine  Clearance = mL/min  x 1.73 m²/ Patient's surface area (m²)

The accuracy of the creatinine clearance calculation depends on the accuracy of the urine collection. Twenty four-hour urine collections are considered optimal because they account for diurnal variation in creatinine clearance. Some laboratories include “grams of creatinine per 24 hours” to the creatinine clearance report. This calculation is valuable in determining if a 24-hour urine collection is complete. Creatinine values <1g/24 hours for men or <0.9g/24 hours for women nearly always mean that the urine collection was incomplete. Normal urine volume is 0.6 to 2.0 liters per day, but most people produce between 1.0 and 1.5 liters per day.  

Creatinine excretion is lower among women, increases with muscle mass, and decreases with age. Nomograms are available to determine a patients age adjusted creatinine clearance percentile rank. Men usually excrete 19 to 26 mg of creatinine per kg of body weight daily and women usually excrete 14 to 21 mg/kg body weight.  The normal range is 1–2 g per 24 hours for men and 0.6–1.5 g per 24 hours for women.  Avoidance of exercise and adequate hydration are important factors in ensuring accurate results.

Renal failure causes reduced creatinine clearance. Creatinine clearance values of 30 to 40 mL/min/1.73 M² suggest moderate renal impairment, while values <28 suggest severe impairment.  

Creatinine clearance may not be accurate in the following medical conditions.

Reference range is 60-180 mL/min/1.73M²

Specimen requirement is a twentyfour hour urine collection in a container without preservative. Instruct the patient to void in the morning and discard the specimen.  All urine is then collected for the next 24 hours, including the next first morning void.  The container should be refrigerated during and after the collection. Patient's height and weight are needed for calculating the clearance. One SST tube of blood is also required for measurement of serum creatinine.

Reference

Acute Kidney Injury Work Group. Kidney disease: improving global outcome: KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2(1):1-138.