Creatinine clearance equation

Digoxin is not extensively metabolized in humans almost two thirds is excreted unchanged by the kidneys. Its renal clearance is proportional to creatinine clearance. Equations and nomograms are available for adjusting digoxin dosage in patients with renal impairment. 

In Chapter 1/ we pointed out that the creatinine clearance equation... 

Equation to adjust measured phenytoin levels in the setting of creatinine clearance <10 mL/min +/- hypoalbuminemia... 

O Equations to estimate creatinine clearance that incorporate a single creatinine concentration (e.g., Cockcroft-Gault) may underestimate or overestimate kidney function depending on whether acute renal failure is worsening or resolving. 

TABLE 22-1. Equations for Estimation of Creatinine Clearance (CrCI)... 

Several equations have been developed to assess unstable kidney function. The Jelliffe equation (Table 22-1) estimates creatinine clearance by considering the change in serum creatinine over a specified time period.11 While it is more mathematically difficult to calculate, it better estimates creatinine clearance in patients with rapidly changing kidney function compared to an equation that only includes a single creatinine concentration. 

Dosing adjustment based on Calvert equation Proportional to lower creatinine clearance, where normal equal to 70 mL/minute (0.67 mL/s x m2)... 

Although determination of creatinine clearance rate is a standard clinical procedure, it is difficult to carry out mainly because accurate collection of total urine output over a 24-hour period is required. It can never be certain that this requirement has been met. Since creatinine is produced continuously in muscle and is cleared by the kidney, renal failure is characterized by elevated serum creatinine levels. The degree of elevation is directly related to the degree of renal failure—if it is assumed that the production of creatinine in the muscle mass is constant and that renal function is stable. When these assumptions are valid, there is a direct relationship between serum creatinine level and kanamycin half-life, as shown in Fig. 9. The equation of the line in Fig. 9 is... 

Step 2 Estimate creatinine clearance Use CockcrofKiault equation to estimate creatinine clearance or calculate creatinine dearance from timed urine collection... 

The decrease of renal function with age is independent of the decrease in creatinine production. Because of the difficulty of obtaining complete urine collections, creatinine clearance calculated in this way is at least as reliable as estimates based on urine collections. Fat-free mass (equation [14]) should be used for obese patients, and correction should be made for muscle wasting in severely ill patients. 

In this equation CLCRj is the actual creatinine clearance of subject i. The fixed effect parameters are now 0 cl corresponding to the clearance of a person with a CLCr of 4 L/h the and 0 clCr as an exponent describing the increase of CLj with CLcr. 

Fig. 2. Mean concentrations at steady state after twice daily 500 mg levofloxacin. The circles and crosses correspondent to the individual CL estimates in male and female patients, respectively. Three filled circles correspond to patients which PK is shown in Figure 1. The lines are calculated using the fit parameters given in Table 1 and Equation 2 for the 2.5%, 50% and 97.5% quantiles. All except two individuals are within these limits. The vertical solid lines mark patients with creatinine clearances of 30 ml/min and 70 ml/min, curves stop at 150 ml/min.

These equations make a number of assumptions and may be used to estimate Mrs RP s renal function this is necessary as toxicity from capecitabine can be increased in individuals with renal impairment (creatinine clearance <50 mL/min). 

The most commonly used equation for estimating creatinine clearance is the Cockcroft-Gault equation. This equation requires knowledge of the patient s gender, age, weight and serum creatinine. The equation is ... 

A commonly used surrogate marker for actual creatinine clearance is the Cockcroft-Gault formula, which employs creatinine measurements and a patient s age and weight to predict the clearance. It is named after the scientists who first published the formula. The equation is popular because it is easy to calculate. 

In routine clinical practice it is not practical to collect the urine samples that are needed to measure creatinine clearance directly. However creatinine clearance in adult patients can be estimated either from a standard nomogram or from equations such as that proposed by Cockcroft and Gault (23). For meiy creatinine clearance can be estimated from this equation as follows ... 

The Cockcroft and Gault equation cannot be used to estimate creatinine clearance in pediatric patients because muscle mass has not reached the adult proportion of body weight. Therefore/ Schwartz and colleagues (25/ 26) developed the following equation to predict creatinine clearance in these patients ... 

For womeii/ this estimate should be reduced by 15%. While this equation estimates creatinine clearance... 

From the standpoint of clinical pharmacology/ the utility of using the Cockcroft and Gault equation/ or other methods/ to estimate creatinine clearance stems from the fact that these estimates can alert healthcare workers to the presence of impaired renal function in patients whose creatinine formation rate is reduced. As discussed in Chapter 5, creatinine clearance estimates also can be used to guide dose adjustment in these patients. 

The AUC measured after administration of a drug dose is related to the extent of drug absorption in the following way. Generalizing from the analysis of creatinine clearance that we presented in Chapter 1/ the first-order differential equation... 

Creatinine clearance The normal CrCI rate for an adult is approximately 1 00 ml/min. The most common equation for estimating renal function is ... 

Pigure 24-9 Relationship between GFR measured using l-iothalamate clearance and estimates of creatinine clearance (CrC ) obtained using the (A) Cockcroft and Gault equation and (B) measured creatinine clearance. (From Coresh JJoto RD, Kirk KA,Whelton PK, Massry S, Jones C, et at. Creatinine clearance os a measure of GFR in screenees for the African-American study of kidney disease and hypertension pilot study. Am J Kidney D/s 1998 32 32-42.)... 

They observed that the MDRD equation provided more accurate assessment of GFR than either the Cockcroft and Gault equation or measured creatinine clearance. The MDRD formula has several advantages (1) it was developed and validated in a large population, (2) it was developed with a population that included both European-Americans and African-Americans, (3) it does not require patient weight, (4) it was validated against an iothalamate clearance estimate... 

The impact of creatinine clearance (CLCr) as a predictor variable for pediatric PM parameters is often low even for renally eliminated drugs due to the inclusion of size (height) in the calculation of renal function and its normalization to adult size. Although the original pediatric renal studies by Schwartz (6) show excellent correlation between measured and estimated CLCr from serum creatinine, others have noted these equations as not predictive in some pediatric subpopulations. The poor precision for the clinical assay of serum creatinine partially accounts for this lack of predictability. However, many pediatric PM analyses have demonstrated the reciprocal of serum creatinine is a powerful covariate for predicting the clearance of renally eliminated drugs, even in infants. 

Initial doses of vancomycin can be computed for adult patients using estimated kinetic parameters derived from population pharmacokinetic data. Clearance is estimated using the patient s creatinine clearance in the following equation" Cl (in mL/min/kg) = 0.695(CrCl in mL/min/kg) -L 0.05. The volume of distribution is computed assuming the standard value of 0.7 L/kg = 0.7(Wt),... 

When estimating creatinine clearance in the elderly using the Cockcroft and Gault equation, some clinicians choose to round the value up to 1 if the patient s serum creatinine concentration is less than 1. Rounding the serum creatinine concentration may provide an underestimation of creatinine clearance and result in improper dose adjustment of renally eliminated medications. It is important to realize that the equation is merely an estimate, and attempts should be made to determine creatinine clearance accurately with certain medications (e.g., metformin). 

Equations to estimate creatinine clearance or GFR are commonly used in ambulatory and inpatient settings, and incorporate patient demographic variables such as serum creatinine, age, gender, weight, and ethnicity. 

Estimation of creatinine clearance in vegetarians is controversial. Some clinicians advocate use of the 24-hour creatinine clearance in these patients since this method is based on the renal clearance of creatinine. The six-variable Modification of Diet in Renal Disease (MDRD) study equation (see below), which incorporates nutritional parameters such as BUN and albumin, has been suggested as an alternative approach. 

TABLE 41—5. Equations for the Estimation of Creatinine Clearance in Adults with Stable Renal Function... 

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