Creatinine clearance direct measurement

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 ... 

Direct measurement of creatinine clearance (CrCl) requires collection of urine over an extended time interval (usually 24 hours) with measurement of urine volume, urine creatinine concentration, and serum creatinine concentration (Table 22-1). Because kidney function can fluctuate significantly during ARF, this method may underestimate or overestimate kidney function depending on whether ARF is worsening or resolving. 

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. 

O Donnel P, Burne M, Nemoto T, Keane WF, RabbFI Direct measurement of renal function in mice with ischemia-reperfusion injury comparison of inulin clearance with serum creatinine, (abstract) J Am Soc Nephrol 11 606A, 2001... 

The measurement of the GFR is of current interest in view of the fact that recent studies have questioned the accuracy of creatinine clearance and serum creatinine level for assessing kidney function and the rate of progression of renal disease (58). To recapitulate the value of the GFR as an index of the severity of renal disease, it should be pointed out that the GFR provides, in a sense, a direct measure of renal function and is reduced relatively early in the course of renal disease. 

In summary, monitoring changes in the creatinine clearance or directly measuring the GFR using markers that are not acted upon by the tubule are the best tools to detect early drug-induced renal toxicity in patients with a normal baseline creatinine concentration. Serial monitoring of the serum creatinine concentration is usually adequate in those chronic failure patients whose creatinine is already increased. The role of other endogenous compounds such as cystatin C as a way to monitor renal function is not yet known. 

C. The measurement of the phosphate excretion index (Nil). Since the phosphate/creatinine clearance ratio is normally directly related in a known manner to plasma phosphate concentration (MIO), the observed Cp/Ccr in any given case can be compared with the normal mean value at the same plasma concentration. The difference is called the Phosphate Excretion Index (PEI) and its normal range is —0.09 to +0.09. The values in hyperparathyroid cases usually lie above the upper normal limit and in hypoparathyroid cases below the lower limit (Nil) (Fig. 10). 

Although direct methods provide a more accurate measurement of GFR for a particular patient, these methods are time-consuming and require analytical methods that are not always readily available. As a result, GFR is routinely estimated based on the endogenous marker, creatinine clearance. Creatinine clearance is most commonly measured indirectly using any number of equations that have been developed based on a patient s measured serum creatinine (5C). These equations are based on patient characteristics such as age, gender, body weight, and height... 

The directly measured creatinine clearance is then calculated by Eq. 4.28 ... 

The direct measurement of clearances normalized to body surface area and body water volume, expressed on a weekly basis, is crucial in the assessment of treatment adequacy. Creatinine and urea clearance are the most widely used adequacy indices in PD and APD. In a steady state, the calculation of clearance, that is, the ratio between dialytic (and renal) solute removal and blood solute concentration, requires quantitation of solute removed by total collection of drained dialysate. Blood and dialysate solute concentrations are measured by standard assays. The ratio of dialysate to blood solute concentration multiplied by the dialysate volume equals the clearance (Van Stone 1989). In APD, the intermittency or variable intensity of the therapy causes a modest compartmental disequilibrium with fluctuation of plasma concentrations between the predialytic (evening) and postdialytic (morning) values (Newman 1995, Calconi 1998). This difference is more marked for urea than for creatinine (Newman 1995). 

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