Creatinine clearance test

Because creatinine is endogenously produced and released into body fluids at a constant rate, its clearance has been measured as an indicator of GFR. A protocol for the conduct of the creatinine clearance test may be found in the third edition of this textbook. 

Kidney function is tested by the creatinine clearance test. A decrease in GFR causes an increase in creatinine in semm and a decrease in creatinine in urine. The results of the creatinine clearance test vary with age and whenever there is decreased muscle mass. 

The picture is not totally clear but it seems possible that the previous use of cisplatin causes kidney damage that may not necessarily be detectable with the usual creatinine clearance tests, llie effect is to cause a marked reduction in the clearance of the methotrexate. The serum methotrexate levels of such patients should be closely monitored so that any delay in its clearance is detected early and folinic acid rescue therapy can be given. This appears to prevent serious toxicity. " ... 

This order suggests that the anionic complexes would be more toxic to the kidney than the cationic complexes and that trans-[Pt(NH3)2Cl2] would be more toxic than ci8-[Pt(NH3)2Cl2]. The trans/ois order of kidney retention (toxicity) is exactly the reverse of that found for whole animal toxicity. It would be interesting to see if kidney toxicity, as measured by BUN (blood urea nitrogen) and creatinine clearance tests, would Indeed parallel this predicted order based on gross organ uptake. 

Creatine is an amino acid but is not a component of proteins. It is made from arginine and is metabolised to creatinine prior to excretion in the urine (Chapter 44). Blood levels of creatinine and the creatinine clearance test are used to evaluate glomerular filtration in renal disease. NB Do not be confused between creatine, creatinine and carnitine. 

Measurement of serum creatinine may not however be a sensitive indicator of early renal failure, since it may remain within normal limits even though the glomerular filtration rate is reduced by half. Also, when plasma levels are above normal, creatinine can be excreted through the tubules. The creatinine clearance test is a more useful test as it approximates to the glomerular filtration rate. This is a sensitive test for measuring renal impairment. 

Monitor for adequate perfusion of vital organs through assessment of mental status, creatinine clearance, liver function tests, and a stable HR between 50 and 100 beats per minute. Additionally, adequate skin and muscle blood perfusion and normal pH is desirable. 

Prior to initiating treatment with a LMWH, baseline laboratory tests should include PT (prothrombin time)/INR, aPTT, complete blood cell count (CBC), and serum creatinine. Monitor the CBC every 3 to 4 days during the first 2 weeks of therapy, and every 2 to 4 weeks with extended use.5 Use LMWHs cautiously in patients with renal impairment. Specific dosing recommendations for patients with a creatinine clearance (CrCl) less than 30 mL/minute are currently available for enoxaparin but lacking for other agents of the class (Table 7-3). Current guidelines recommend the use of UFH over LMWH in patients with severe renal dysfunction (CrCl less than 30 mL/minute).8... 

Assess kidney function by evaluating a patient s signs and symptoms, laboratory test results, and urinary indices. Calculate a patient s creatinine clearance to evaluate the severity of kidney disease. 

AUC, area under the time-concentration curve ARV, antiretroviral AV, atrioventricular Cmax, maximum concentration CrCI, creatinine clearance ESRD, end-stage renal disease Cl, gastrointestinal HD, hemodialysis LFT, liver function test NRTI, nucleoside reverse transcriptase inhibitor UCT, uridine diphosphate-glucuronsyltransferase. 

P743 was tested on a validated multiple-insult rat model [35] involving transient renal ischemia, dehydration, uninephrectomy and selective injection of a high dose (about 1.8 gl kg ) into the single remaining kidney and was found to have only minimal effects on GFR (evaluated by the endogenous creatinine clearance) and induced moderate enzymuria (NAG release into the final urine) or proteinuria. The effects observed were lower than those of the HOCA diatri-zoate [25]. 

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. 

None of the tested covariates was identified as having a clinically relevant impact on the PK of cetuximab. Thus, changes in dose or dosing regimen do not appear to be necessary in any of the subpopulations defined by these covariates. However, it should be noted that the majority of the studied patients had adequate hepatic and renal function. Overall, more than 90 % of the patients included in the PK database had normal hepatic function, more than 60% had normal renal function, and a further 32% had only mild impairment (creatinine clearance 50-80 mL/min). Hence, the effect of more severe renal or hepatic impairment on cetuximab PK remains to be elucidated. 

We selected one renal hypouricemia patient with a history of ALPE and one healthy adult (control) without a history of ALPE, and measured creatinine clearance, FEUA, and oxidative stress markers (urinary 8-isoprostane and NOx) after anaerobic and aerobic exercise load tests (a 400-m race, 16 min on a treadmill, Bruce method, 13.5metabolic equivalents (METs)) (Fig. 67). In the hypouricemia patient, (a) exercise reduced creatinine clearance (Fig. 68), (b) FEUA increased 5h after the exercise load test (Fig. 69), (c) the urinary 8-isoprostane level increased slightly 6-25h after the exercise load test, although there were no marked differences compared with the control values (Fig. 70), and (d) the urinary NOx level increased 2 and 5h after the exercise load test (Fig. 71). Thus, we found that exercise reduced creatinine clearance in the renal hypouricemia patient with a history of ALPE, but there was no marked influence of oxidative stress. 

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. 

The relationship between renal impairment and the absorption and disposition of HMR1964 (insulin glulisine) will be assessed by regressing pharmacokinetic parameters onto CLcr. Regression parameter estimates ( standard error) with confidence intervals and coefficients of correlation (Pearson) with p-values for test of difference from zero will be reported. Scatter plots of the concentration time profiles and pharmacokinetic parameters against creatinine clearance will be produced. 

Hepatic and renal function. Patients with advanced cancer may have impaired liver function due to the presence of liver metastases. In this case drug doses may need to be adjusted. In the case of the FOLFOX regimen, 5-fluorouracil dose may need to be reduced if the impairment is moderate or severe. Mrs KT s baseline liver function tests indicate a normal liver function, but these parameters should be monitored carefully throughout treatment. Reduced renal function may also necessitate a decrease in drug dosage. In the case of the FOLFOX regimen, oxaliplatin is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min). 

As renal function improves, the excretion of urea increases and the concentration of urea in blood declines. So a reduction in blood urea nitrogen (BUN) is also a useful sign of returning kidney function. More complex tests, such as creatinine clearance, would be needed to check whether the glomerular filtration rate (GFR) has returned to normal. 

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 ... 

BLEOMYCIN ANTICANCER AND IMMUNOMODULATING DRUGS-CISPLATIN t bleomycin levels, with risk of pulmonary toxicity Elimination of bleomycin is delayed by cisplatin due to 1 glomerular filtration. This is most likely with accumulated doses of cisplatin in excess of 300 mg/m2 Monitor renal function and adjust dose of bleomycin as per creatinine clearance. Monitor clinically, radiologically and with lung function tests for pulmonaiy toxicity... 

IFOSFAMIDE CISPLATIN t risk of neurotoxicity, haematotoxicity and tubular nephrotoxicity of ifosfamide due to t plasma concentrations of ifosfamide Cisplatin tends to cause renal damage, which results in impaired clearance of ifosfamide Do renal function tests before initiating therapy and during concurrent therapy, and adjust dosage based on creatinine clearance values. Advise patients to drink plenty of water -vigorous hydration - and consider mesna therapy for renal protection... 

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. 

Creatinine has no useful function and is eliminated by renal glomerular filtration and to a small extent by renal tubular secretion. Creatinine clearance approximately parallels the glomerular filtration rate (GFR) and is used as a kidney function test. It is calculated as follows ... 

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