Creatinine clearance estimation

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. 

Luke DR, Halstenson CE, Opsahl JA, et al. Validity of creatinine clearance estimates in the assessment of renal function. Clin Pharmacol Ther... 

Davis GA, Chandler MHH. Comparison of creatinine clearance estimation metiiods in patients with trauma. Am J Healtii Syst Pharm 1996 53 1028-1032. 

Avoid or use cautiously if patient s estimated creatinine clearance is <20 mL/min... 

Obtain a baseline serum creatinine measurement. Calculate the estimated creatinine clearance and adjust the dose of H2RAs and sucralfate according to package insert recommendations. 

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. 

FIGURE 56-2. Treatment algorithm for gout and hyperuricemia. Renal insufficiency is defined as an estimated creatinine clearance (CrCI) of less than 30 mL/minute. IA, Intraarticular NSAID, nonsteroidal anti-inflammatory drug. 

Formulas for Estimating Creatinine Clearance in Patients with Stable Renal Function... 

Formula for Estimating Creatinine Clearance from a Measured Urine Collection... 

Traub SI, Johnson CE. Comparison of methods of estimating creatinine clearance in children. Am J Hosp Pharm 1980 37 195-201. 

Creatinine clearance The rate at which creatinine is filtered across the glomerulus an estimate of glomerular filtration rate. 

Renal function can be grossly assessed by hourly measurements of urine output, but estimation of creatinine clearance based on isolated serum creatinine values in critically ill patients may yield erroneous results. Decreased renal perfusion and aldosterone release result in sodium retention and, thus, low urinary sodium (<30 mEq/L). 

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

Serum creatinine is not a good measure of renal function in elderly because muscle mass is reduced and the production of creatinine is thus reduced. Estimation of GFR based on serum creatinine is therefore not accurate enough in the elderly (Baracskay et al. 1997). Creatinine clearance should be used instead. Another possibility is measurement of cystatin C in plasma. The rate of production of cystatin C is relatively constant so it seems to be a more reliable estimation of GFR also in older adults. 

From a scientific point of view, glomerular filtration rate (inulin or creatinine clearance) is the best global estimate of renal function. Other parameters of interest include, but are not limited to ... 

The isotope tracer method for estimating the total muscle mass of an organism by determining the amount of creatinine clearance. The method relies on the fact that muscle creatine phosphate is converted to creatine, and the latter is metabolized into creatinine. 

The patient s renal function, preferably evaluated on the basis of estimated creatinine clearance (Ccr). 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

It is well known that both glomerular and tubular renal functions decline with age in at least one third of individuals. As a result there is greater variation in renal function in older subjects. Glomerular filtration rate can be predicted by creatinine clearance, which can be estimated based on measured serum creatinine (Sercr) concentration. One such formula is the Cochrane and Gault formula in which... 

The effect of age on the renal elimination of some drugs is shown in Table 2. In general, the dose can be guided by the estimated or measured creatinine clearance. This should be performed in particular... 

Drusano GL, Munice HL Jr, Hoopes JM, et al Commonly used methods of estimating creatinine clearance are inadequate for elderly debilitated nursing home patients. I Am Geriatr Soc 1988 36 437-441. 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

Drugs cleared by the renal route often require adjustment of clearance in proportion to renal function. This can be conveniently estimated from the creatinine clearance, calculated from a single serum creatinine measurement and the predicted creatinine production rate. 

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. 

Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dosage must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the rate-corrected QT interval (QTC) and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 bpm and hypokalemia are relative contraindications to its use. 

For women, the result should be multiplied by 0.85 (because of reduced muscle mass). It must be emphasized that this estimate is, at best, a population estimate and may not apply to a particular patient. If the patient has normal renal function (up to one third of elderly patients), a dose corrected on the basis of this estimate will be too low—but a low dose is initially desirable if one is uncertain of the renal function in any patient. If a precise measure is needed, a standard 12- or 24-hour creatinine clearance determination should be obtained. As indicated above, nutritional changes alter pharmacokinetic parameters. A patient who is severely dehydrated (not uncommon in patients with stroke or other motor impairment) may have an additional marked reduction in renal drug clearance that is completely reversible by rehydration. 

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