What should creatinine (Cr) clearance be?

From the Guidelines

Creatinine clearance (CrCl) should typically be greater than 60 mL/min in adults with normal kidney function. For healthy young adults, normal values range from 90-140 mL/min for men and 80-125 mL/min for women. Creatinine clearance naturally decreases with age, with an expected decline of approximately 1 mL/min per year after age 40. When CrCl falls below 60 mL/min, it indicates moderate kidney dysfunction, while values below 30 mL/min represent severe impairment. These values are important because many medications require dosage adjustments when CrCl drops below certain thresholds, typically at 60, 30, and 15 mL/min.

Key Points to Consider

• Creatinine clearance reflects how efficiently the kidneys filter waste products from the blood, making it a valuable indicator of kidney function.
• It's calculated using serum creatinine levels, age, weight, and gender, with the Cockcroft-Gault equation being commonly used for this purpose, as seen in the study by Launay-Vacher et al. 1.
• Regular monitoring of creatinine clearance is essential for patients with chronic kidney disease, diabetes, hypertension, or those taking potentially nephrotoxic medications.
• The Cockcroft-Gault equation is a widely used method for estimating CrCl, but it has its limitations, particularly in patients with severe renal impairment or decreased muscle mass, as noted in the study by Launay-Vacher et al. 1.
• Other studies, such as those published in the Journal for ImmunoTherapy of Cancer 2 and the European Heart Journal 3, also emphasize the importance of monitoring CrCl in patients with various medical conditions.
• The most recent and highest quality study, published in the Journal for ImmunoTherapy of Cancer 2, recommends that creatinine clearance should be greater than 60 mL/min for patients to tolerate certain medications, further supporting the importance of monitoring CrCl.

From the FDA Drug Label

TABLE 4 DOSAGE ADJUSTMENT GUIDE FOR PATIENTS WITH RENAL IMPAIRMENT (Dosage at Eight-Hour Intervals After the Usual Initial Dose) Serum Creatinine (mg %) Approximate Creatinine Clearance Rate (mL/min/1.73m 2) Percent of Usual Doses Shown Above ≤1 > 100 100 1.1 to 1.3 70 to 100 80 1.4 to 1.6 55 to 70 65 1.7 to 1.9 45 to 55 55 2 to 2.2 40 to 45 50 2.3 to 2.5 35 to 40 40 2.6 to 3 30 to 35 35 3.1 to 3. 5 25 to 30 30 3.6 to 4 20 to 25 25 4.1 to 5.1 15 to 20 20 5.2 to 6.6 10 to 15 15

6. 7 to 8 < 10 10

Creatinine Clearance Rates for gentamicin dosage adjustment are as follows:

• > 100 mL/min/1.73m^2: no adjustment needed
• 70 to 100 mL/min/1.73m^2: 80% of usual dose
• 55 to 70 mL/min/1.73m^2: 65% of usual dose
• 45 to 55 mL/min/1.73m^2: 55% of usual dose
• 40 to 45 mL/min/1.73m^2: 50% of usual dose
• 35 to 40 mL/min/1.73m^2: 40% of usual dose
• 30 to 35 mL/min/1.73m^2: 35% of usual dose
• 25 to 30 mL/min/1.73m^2: 30% of usual dose
• 20 to 25 mL/min/1.73m^2: 25% of usual dose
• 15 to 20 mL/min/1.73m^2: 20% of usual dose
• 10 to 15 mL/min/1.73m^2: 15% of usual dose
• < 10 mL/min/1.73m^2: 10% of usual dose 4 5

From the Research

Creatinine Clearance Values

• The normal creatinine clearance (CrCl) value can vary depending on age and gender, with a decrease in CrCl of approximately 10 mL/min per decade in men and 11 mL/min per decade in women 6.
• In a study of ambulatory adults, the 2.5th centiles for CrCl values ranged from 105 mL/min in men aged 18-30 years to 53 mL/min in men aged 71-80 years, and from 85 mL/min in women aged 18-30 years to 42 mL/min in women aged 71-80 years 6.
• Augmented renal clearance (ARC), defined as a CrCl of ≥ 130 mL/min, has been observed in 14%-80% of critically ill patients and is associated with therapy failures for renally cleared drugs 7.
• In trauma patients, ARC was found to occur in more than half of all high-risk patients and was underestimated by standard clinical equations, with a median CrCl of 154 mL/min 7.

Factors Affecting Creatinine Clearance

• Age and gender are significant factors affecting CrCl, with CrCl decreasing with age and being lower in women than in men 6.
• Male gender, younger age, and lack of comorbidities such as hypertension and diabetes are associated with higher CrCl values 7.
• Packed red blood cells transfusion is associated with lower CrCl values 7.

Clinical Implications

• ARC is not associated with increased incidence of venous thromboembolism or infection, but rather is associated with younger, healthier males and reduced mortality 7.
• The use of estimated glomerular filtration rate (eGFR) equations, such as the Cockcroft-Gault equation, may not accurately predict CrCl in critically ill patients, particularly those with ARC 8, 9, 10.
• Measured CrCl using urinary collection is recommended in patients suspected of displaying ARC, as estimated renal clearances may show poor agreement with measured CrCl values 8.