Normalized to creatinine

Under field exposure conditions, it is recommended to measure PA herbicides in 24-hr urine samples collected starting at the end of the work-shift. Spot samples collected at the end of exposure or the following morning can be used when a 24-hr urine collection is impractical. In this case, the concentration of the compounds should be normalized to creatinine concentration or adjusted for specific gravity. 

Either 24 hour urine collection or timed urine samples collected at the same time each day is recommended, with the activity expressed per unit of time (Price 1982, Plummer et al. 1986). If the assessment is to be repeated with time, the samples should be collected over the same time period on each day because there is pronounced diurnal variation in excretion rate of some enzymes (Maruhn et al. 1977, Price 1982, Gossett et al. 1987). For spot urine samples or those where accurate timed collection is not possible, normalization of activity per unit of creatinine can be done and this has been shown to be reasonably well correlated to 24 hour enzyme activity (Vanderlinde 1981, Grauer et al. 1995). Diet and age-matched controls must be included if enzyme activity is to be normalized to creatinine, to control for the effects of these variables on creatinine excretion (Plummer et al. 1986, Casadevall et al. 1995). 

The inherent limitations of the Jaffe method for determination of creatinine have been discussed in section Assessment of Renal Injury by Serum Chemistry . Factors which result in reduced excretion of creatinine without acute tubular injury (e.g., chronic renal disease in aged animals with pronounced loss of nephron mass, prerenal reduction of GFR) will also result in reduced urine creatinine and falsely elevated enzyme activity when normalized to creatinine (Price 1982, Plummer et al. 1986, Casadevall et al. 1995). 

In the comprehensive study of the uranium and thorium levels in urine of 500 US residents, a magnetic sector ICPMS with a microconcentric nebulizer was used (Ting et al. 1999). The sample handling was carried out in a clean laboratory and all reagents were of high purity in order to avoid cross contamination. The samples were spiked with iridium that served as an internal standard and the creatinine concentration was also determined in order to normalize the results. The distribution of the uranium concentration, normalized to creatinine is shown in the top frame of Figure 4.12 while the bottom frame shows the frequency distribution of uranium in 350 urine samples in Israel (Karpas et al. 1996). 

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. 

For a drug that is to be developed for a disease that occurs mainly in the elderly, it is often advisable to evaluate tolerability and pharmacokinetics in healthy elderly volunteers before clinical trials in the patient population. Dosage may need to be reduced and particular care taken when the kidney is the major organ of elimination, which should be established in the healthy young before administration to the elderly. It should be remembered that the GFR in the healthy elderly with normal plasma creatinine and urea is generally much lower than that in the young. One reason why healthy elderl/ studies have... 

Renal function impairment- In patients receiving pamidronate for bone metastases who show evidence of deterioration in renal function, withhold treatment until renal function returns to baseline. In a clinical study, renal deterioration was defined as follows for patients with normal baseline creatinine, an increase of 0.5 mg/dL for patients with abnormal baseline creatinine, an increase of 1 mg/dL. In this clinical study, pamidronate treatment was resumed only when the creatinine returned to within 10% of the baseline value. In other indications, clinical judgment should determine whether the potential benefit outweighs the potential risk in such patients. 

In fact elderly people have a reduced creatinine clearance, often balanced by the decline in creatinine input with a resulting normal serum creatinine. This is clinically important because drugs which are cleared through the kidneys need to be given in scaled down amounts to prevent cumulation and possible toxicity - e.g., gentamicin and other parenteral aminoglycosides, digoxin. 

Digoxin is not extensively metabolized in humans almost two thirds is excreted unchanged by the kidneys. Its renal clearance is proportional to creatinine clearance and the half-life is 36-40 hours in patients with normal renal function. Equations and nomograms are available for adjusting digoxin dosage in patients with renal impairment. 

However, creatinine is sometimes a poor predictor of renal function. For example, it must be related to muscular mass and the normal serum creatinine may be too high in a person of 50 kg and little muscle. It is therefore better to use creatinine clearance below 60 ml/min as a criterion. 

This non-invasive method allows to follow an experiment longitudinally, and relates to more than one skeletal tissue. Care has to be taken however to not only normalize the values in respect to creatinine levels, in order to compensate for individual differences in urine concentration, but also to either collect the samples over a longer period than 24 h, as proposed by Smith et al. (2004), or to collect each time at the same hour to exclude the known circadian variation in excretion (Stone et al. 1998). In addition, when using female animals, the measurements should be recorded regularly over a longer period to correct for considerable peak variation during the estrous cycle (Blanque etal. 2001). 

We have measured FSH in unextracted urine on an AxSYM random-access immunoassay analyzer (Abbott laboratories, Abbott Park, IL) with a MEIA (microparticle enzyme immuno assay) reagent kit. In order to correct for dilution, creatinine was measured, and the urinary FSH was normalized for creatinine concentration. Urine and serum samples were obtained from 40 women between 32 and 55 years of age. All women were healthy, except for a benign gynecological illness for which they were admitted to our hospital. All women had normal renal function. On the day of operation, we took six serum samples from each patient, each at least an hour apart, in order to calculate the mean serum FSH concentration. During the same day, we collected an early-morning urine sample, 24-h urine sample, and a random void urine sample. 

Increased levels of pseudouridine have been reported to be present in the urine of patients with various types of cancer (Al, M20, Wl, W2). Since pseudouridine is only found in RNA, Kuo et al. (K38) developed a sensitive RPLC method for the rapid determination of urine pseudouridine levels. In a study of 10 colon cancer patients, they reported that 9 exhibited higher than normal pseudouridine-to-creatinine ratios. Davis et al. (D2) have also investigated urine ribonucleoside distribution patterns in patients with advanced colon cancer and report increased levels of I-methylinosine, 1-methylguanosine, 2-methyIguanosine, adenosine, and N. N -dimethylguanosine when compared to normal urine controls. Figure 17 illustrates the advanced colon cancer and normal urine chromatographic profiles. 

A 72-year-old man was treated with ceftriaxone (2 g bd) and gentamicin (80 mg tds) for a severe urinary tract infection (75). On day 5 his serum potassium concentration was 3 mmol/1 with a normal serum creatinine and urine examination. Despite treatment with oral potassium chloride plus a high potassium diet, his serum potassium fell to 2.3 mmol/1 4 days later, accompanied by inappropriate kaliuresis, hypouricemia with inappropriate uri-cosuria, and hypophosphatemia with inappropriate phosphaturia. There was no bicarbonate wasting, but there was proteinuria 1.2 g/day, with a predominance of low molecular weight proteins in contrast, serum creatinine was normal and creatinine clearance was 78 ml/minute. The aminoglycoside was withdrawn with subsequent progressive improvement in renal proximal tubular function, which normalized 9 days later. 

Ventricular dysrhythmias have been reported after rapid infusion of large doses of DAMB (70) in patients with hyperkalemia and renal insufficiency, but not in patients with normal serum creatinine and potassium concentrations, even if they have received the drug over a period of 1 hour. Slower infusion rates and infusion during hemodialysis have been advocated in patients with terminal kidney insufficiency, in order to avoid hyperkalemia. 

Radiocontrast-induced renal ischemia may have contributed to the pathogenesis of the dextran-induced renal insufficiency, as has been shown in animal studies. The mechanism of dextran-induced acute renal insufficiency may be multifactorial, with elements of hyperoncotic acute renal insufficiency, tubular obstruction, and direct tubular toxicity. Radiocontrast-induced acute renal insufficiency is unusual in patients with normal baseline creatinine concentrations. The ischemic effect of radiocontrast seemed to be important in this case. Renal function should be carefully monitored if the simultaneous administration of dextran and radiocontrast is necessary. If renal function deteriorates and oliguria or anuria occurs, plasmapheresis may be an appropriate and effective approach for clearing dextran. 

The use of contrast media in patients taking metformin should be carried out cautiously. Contrast-induced nephropathy can lead to retention of metformin and lactic acidosis. However, there is no conclusive evidence that intravascular contrast agents precipitate metformin-induced lactic acidosis in patients with normal serum creatinine concentrations (under 130 pmol/1). This complication was almost always observed in non-insulin dependent diabetic patients with abnormal renal function before injection of contrast media (4,316). 

Isepamicin is given intravenously or intramuscularly in a dosage of 15 mg/kg/day or 7.5 mg/kg bd. It is not bound to plasma proteins, it distributes in extracellular fluids, and it enters some cells (outer hair cells, kidney cortex) by an active transport mechanism (1) the transference of isepamicin to the bone marrow is excellent (3). Isepamicin is not metabolized and is renally excreted with a half-life of 2-3 hours in adults with normal renal function. Its clearance is reduced in neonates, and a dose of 7.5 mg/kg/day is recommended in children younger than 16 days. Its clearance is also reduced in elderly people, but no dosage adjustment is required. In patients with chronic renal impairment, isepamicin clearance is proportional to creatinine clearance. 

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