Creatinine clearance rates

The study of the mechanism of urinary excretion of amylase and the amylase clearance has been the subject of many studies in recent years. Levitt et. al (79) studied the renal clearance of amylase in renal insufficiency, acute pancreatitis and macro-amylasemia. In acute pancreatitis, the kidney cleared amylase at a markedly increased rate. The ratio of the amylase clearance rate to the creatinine clearance rate (Cgm/Ccr) averaged 3 times normal early in the course of acute pancreatitis, and this elevation could persist after the serum amylase returned to normal. Comparison of an lase clearance to creatinine clearance was to minimize irrelevant changes due to variation in renal function. The increased clearance of amylase makes the urinary amylase a more sensitive indicator of pancreatitis. 

CBP Cromolyn-binding protein CCK Cholecystokinin CCR Creatinine clearance rate CD Cluster of differentiation (a system of nomenclature for sur ce molecules on cells of the immune system) cluster determinant CDl Cluster of differentiation 1 also known as MHC class I-like surfitce glycoprotein... 

Example. Kanamycin is a member of the aminoglycoside class of antibiotics, all of which are eliminated exclusively by glomerular filtration. Creatinine is a natural body substance that is cleared almost exclusively by glomerular filtration, and creatinine clearance rate is frequently used as a diagnostic tool to determine glomerular filtration rate. The relationship... 

Fig. 8 Plot of kanamycin clearance rate versus creatinine clearance rate.

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... 

Renal function is an indication of the physiological state of the kidney glomerular filtration rate (GFR) describes the flow rate of Altered fluid through the kidney, while creatinine clearance rate (Ccr) is the volume of blood plasma that is cleared of creatinine per unit time, and is a useful measure for approximating the GFR. Most clinical tests use the plasma concentrations of the waste substances of creatinine and urea, as well as electrolytes, to determine renal function. The nephron is the functional unit of the kidney (Figure 10.1) it consists of two parts ... 

A small but clinically important amount of creatinine is excreted in the urine daily, and the creatinine clearance rate is often used as an indicator of kidney function. 

Because LMWHs are eliminated renally and patients with renal insufficiency generally have been exclnded from clinical trials, some practice protocols recommend UFH for patients with creatinine clearance rates of less than 30 mL/min. (Creatinine clearance is calculated based on total patient body weight.) However, recent recommendations for dosing adjnstment of enoxaparin in patients with creatinine clearances between 10 and 30 mL/min are now listed in the product manufacturer s label (see Table 16 ). Administration of LMWHs should be avoided in dialysis patients. UFH is monitored and the dose adjusted to a target aPTT, whereas LMWHs are administered by a fixed, weight-based dose. Other dosing information and contraindications are described in Table 16. ... 

The kidneys receive about 20% of the cardiac output (blood flow) and filters approximately 125 ml of plasma per minute. As the patient loses kidney function, the quantity of plasma filtered per minute decreases with an accompanying decrease in clearance. The most useful estimation of creatinine clearance rate (CCr) is obtained using the following empirical formula based on the patient s age and serum creatinine level. 

Alternatively, in toxicology studies, GFR can be estimated by measuring creatinine clearance rate, which is the volume of blood plasma that is cleared of creatinine per unit time (Hart 2005). Creatinine is produced naturally by muscle, and concentrations in blood remain broadly at steady state. It is freely filtered by the glomerulus, but because of additional active secretion by the peritubular capillaries, creatinine clearance slightly overestimates actual GFR. 

Lead nephropathy as a toxicological topic has presented various interpretive clinical and empirical dilemmas. Some appear to have resolved to some extent. Some are mainly confined to nephropathic responses per se. Some are shared with other lead-associated toxic endpoints. A classical endpoint in Pb-induced nephropathy is a reduced estimated or measured glomerular filtration rate (GFR), typically employing creatinine clearance rates, in tandem with measurements of blood urea nitrogen (BUN) and serum creatinine levels. Such declines in GFR are proportional to the level of PbB in chronic injury, subsequent to any transitory hyperfiltration. 

Three of the NAS assessments entailed cross-sectional epidemiological analytical designs. Payton et al. (1994) reported that In-transformed PbB was negatively associated with In calculated creatinine clearance for 744 men evaluated between 1988 and 1991. Kim et al. (1996), in the cross-sectional portion of their NAS analyses, found a significant positive association of In-transformed PbB with concurrent serum Pb. Wu et al. (2003) evaluated a subset of the cohort (total N = 709 670 given full assessment) with respect to PbB, tibial Pb, and patellar Pb as exposure markers and both serum creatinine and estimated creatinine clearance rate as endpoints. They noted a... 

Yamasaku et al. (1980) studied the pharmacokinetics of cefmetazole in four adult volunteers (Table VIII). The dose response in serum concentrations after a 2-hr infusion of 0.5, 1.0, and 2.0 g was excellent. The serum concentration achieved immediately after 1.0 g administered by intravenous infusion was 50 xg/ml. Mean urinary recovery after 24 hr was 83%. The renal clearance rate (116 ml/min) was approximately the same as the creatinine clearance rate (115 ml/min). 

Luthy et al. (1979) studied the pharmacokinetics of cefotaxime in healthy human volunteers. Doses of 0.5, 1, and 2 g of cefotaxime were administered by intravenous infusion over 15 min. Concentrations of cefotaxime in the serum measured just after the end of the infusion were 41, 93, and 160 p.g/ml, respectively. With increasing doses, serum concentrations rose in a nonlinear fashion as the result of a decrease in total body clearance. Renal clearance of cefotaxime modestly exceeded the creatinine clearance rate, which suggests some tubular secretion. This was confirmed in studies using probenecid (Bax et al., 1980). The mean plasma half-life was 1.25 hr. Sixty percent of the administered dose was excreted in the urine. Protein binding was 30% (Neu et al., 1979a). 

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