Renal function tests creatinine measurement

A concern with AUC-targeting based on renal function surrounds the measurement of creatinine clearance. The formulas of Calvert et al. were developed using EDTA clearance, measurement of which is not widely available. They have shown that neither standard measured creatinine clearance, nor the calculation of this index are as accurate or as reproducible. To circumvent this difficulty an alternative dosing strategy has been developed by Chatelut, Canal and co-workers [226], This dosing approach is being tested in clinical trials. 

In safety pharmacology, a number of renal functional tests, such as creatinine and electrolyte measurements, can be supported by most clinical chemistry laboratories (Kinter, Gossett, and Kerns 1994 Seuter 1996 ICH 2000). In some of the later chapters discussing assessments of hepatotoxicity and renal toxicity, a few functional tests are mentioned. Although it may be desirable to include function tests in repeated-dose toxicity studies, given the additional and sometimes invasive procedures, these tests may be better performed by incorporation into single-dose toxicity studies or separate additional studies (Matsuzawa et al. 1997). 

INEFFECTIVE TISSUE PERFUSION RENAL The patient taking an aminoglycoside is at risk for nephrotoxicity. The nurse measures and records the intake and output and notifies the primary health care provider if the output is less than 750 ml/day. It is important to keep a record of the fluid intake and output as well as a daily weight to assess hydration and renal function. The nurse encourages fluid intake to 2000 ml/day (if the patient s condition permits). Any changes in the intake and output ratio or in the appearance of the urine may indicate nephrotoxicity. The nurse reports these types of changes to the primary health care provider promptly. The primary health care provider may order daily laboratory tests (ie, serum creatinine and blood urea nitrogen [BUN]) to monitor renal function. The nurse reports any elevation in the creatinine or BUN level to tiie primary health care provider because an elevation may indicate renal dysfunction. 

RISK FOR INEFFECTIVE TISSUE PERFUSION RENAL When the patient is taking a drag tiiat is potentially toxic to die kidneys, die nurse must carefully monitor fluid intake and output. In some instances, die nurse may need to perform hourly measurements of die urinary output. Periodic laboratory tests are usually ordered to monitor the patient s response to therapy and to detect toxic drag reactions. Seram creatinine levels and BUN levels are checked frequentiy during the course of therapy to monitor kidney function. If the BUN exceeds 40 mg dL or if the serum creatinine level exceeds 3 mg cIL, the primary health care provider may discontinue the drug therapy or reduce the dosage until renal function improves. 

A measurement of renal function (creatinine and/or BUN) is an essential test for most clinical studies, as is the inclusion of an panel of liver function tests (SGOT, SGPT, LDH, CPK, GGT, and/or alkaline phosphatase). The specific tests chosen to be included in a study are somewhat dependent on both the investigator s and/or clinical scientist s experiences and the characteristics of the drug. Other important parameters to measure include serum electrolytes and at least some of the tests listed in Table 20.12. 

Ototoxicity Perform audiometric measurements and assessment of vestibular function prior to initiation of therapy and at regular intervals during treatment. Nephrotoxicity Perform regular tests of renal function throughout treatment, and reduce dose in patients with renal impairment. Renal injury with tubular necrosis, elevation of BUN or serum creatinine, and abnormal sediment have been noted. Reduce the dosage or withdraw the drug. 

While low serum cholesterol levels have been observed in malnourished patients, largely as a result of decreased synthesis of lipoproteins in the liver, hypocholesterolemia occurs later in the course of malnutrition and is therefore not useful as a screening test. PEM usually results in low serum urea nitrogen (BUN), urinary urea, and total nitrogen. Estimation of 24-h urine creatinine excretion is also a valuable biochemical index of muscle mass (when there is no impairment in renal function). The urinary CHI is correlated to lean body mass and anthropometric measurements. In edematous patients, for whom the extracellular fluids contribute to body weight and spuriously high body mass index values, the decreased CHI values are especially useful in diagnosing malnutrition. 

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 ... 

These include mesalazine, metformin, NSAIDs, tetracyclines (except doxycycline and minocycline), chloramphenicol, lithium, methotrexate, chloroquine, fibrates, chlorpropamide and glibenclamide, Clinically, it is useful to measure urine output per hour or per 24 hours as a fall in urine output in the presence of adequate fluid intake often indicates or warns of some impairment of renal function. Furthermore, it is neither expensive nor time-consuming to perform a quick test for albumin, casts and red cells in the urine, and to measure pH. Creatinine clearance values are often used to determine the safe doses for several drugs (e.g. NSAIDs, ciclosporin). 

Data on biological variability are used to assist in the selection of the most appropriate test in a given situation. For example, creatinine clearance and urine creatinme have less intraindividual variation than serum creatinine so that creatinine clearance is a better choice than serum creatinine for initial assessment of renal function in an individual but the lower RCV for serum creatinine make this test better for monitoring individuals. However, the need for a urine collection reduces the practicality of using clearance in the initial assessment of renal function. Studies to determine whether the GFR calculated from the serum creatinine concentration might enhance the utility of the serum measurement still have to be performed. 

Early kidney disease is difficult to detect. The urinalysis is normal in early lead nephropathy and the blood urea nitrogen and serum creatinine increase only when two-thirds of kidney function is lost. Measurement of creatinine clearance can often detect earlier disease as can other methods of measurement of glomerular filtration rate. An abnormal Ca-EDTA mobilization test has been used to differentiate between lead-induced and other nephropathies, but this procedure is not widely accepted. A form of Fanconi syndrome with aminoaciduria, glycosuria, and hyperphosphaturia indicating severe injury to the proximal renal tubules is occasionally seen in children. 

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