Creatinine clearance calculation

Calculate measured creatinine clearance Calculate fractional excretion of sodium Plans for renal replacement... 

Drugs cleared by the renal route often require adjustment of clearance in proportion to renal function. This can be conveniently estimated from the creatinine clearance, calculated from a single serum creatinine measurement and the predicted creatinine production rate. 

The decrease of renal function with age is independent of the decrease in creatinine production. Because of the difficulty of obtaining complete urine collections, creatinine clearance calculated in this way is at least as reliable as estimates based on urine collections. Fat-free mass (equation [14]) should be used for obese patients, and correction should be made for muscle wasting in severely ill patients. 

Obtain a baseline serum creatinine measurement. Calculate the estimated creatinine clearance and adjust the dose of H2RAs and sucralfate according to package insert recommendations. 

Several equations have been developed to assess unstable kidney function. The Jelliffe equation (Table 22-1) estimates creatinine clearance by considering the change in serum creatinine over a specified time period.11 While it is more mathematically difficult to calculate, it better estimates creatinine clearance in patients with rapidly changing kidney function compared to an equation that only includes a single creatinine concentration. 

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. 

Step 2 Estimate creatinine clearance Use CockcrofKiault equation to estimate creatinine clearance or calculate creatinine dearance from timed urine collection... 

The creatinine clearance, CW, is calculated by using the following formulae ... 

To minimize the risk of induced arrhythmia, patients initiated or reinitiated on Betapace or Betapace AF should be placed for a minimum of 3 days (on their maintenance dose) in a facility that can provide cardiac resuscitation, continuous electrocardiographic monitoring, and calculations of creatinine clearance. For detailed instructions regarding dose selection and special cautions for people with renal impairment, see Administration and Dosage. 

Maintain normal sinus rhythm after conversion from atrial fibrillation or flutter PO Individualized using a seven-step dosing algorithm dependent upon calculated creatinine clearance and QT interval measurements. 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

The risk interpretation of biomonitoring results will tend to have additional uncertainties. That is because, in addition to the standard uncertainties encountered in risk assessment, there is the uncertainty of extrapolating from a blood or urinary concentration to an external dose. There will be variability both in the timing between sample draw and most recent exposure and in the relationship between blood concentration and dose. Those kinds of variability are compounded by uncertainty in the ability of a PK calculation or model to convert biomarker to dose accurately. For example, reliance on urinary biomarker results expressed per gram of urinary creatinine leads to an uncertain calculation of total chemical excretion per day because of the considerable variability in creatinine clearance per day. That complicates an otherwise simple approach to estimating dose. Furthermore, the conversion requires knowledge of fractional excretion via various pathways, which may not be present for a large sample of humans. The uncertainties created by these factors can be bounded via sensitivity and Monte... 

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. 

Endogenous creatinine clearance may also be used to estimate GFR. A single timed urine collection and matched plasma sample are used. Clearance is calculated as noted above. 

The volume of urine collected over 24 h and the concentration of creatinine were determined to allow the subjects creatinine clearance to be calculated. 

A 24 h urine sampling was performed during the IV dosing period of the study that started on Day 1 and ended on Day 2. The volume of urine collected and the concentration of creatinine were determined to allow the creatinine clearance to be calculated. 

Fig. 1. Individual concentration time courses. CONC creatinine clearance, PRED model predictions for the population with r = 0, IPRE model predictions for the individual subject with random q j, CLcr creatinine clearance in L/h is calculated as left hand scale 10/4...

Fig. 2. Mean concentrations at steady state after twice daily 500 mg levofloxacin. The circles and crosses correspondent to the individual CL estimates in male and female patients, respectively. Three filled circles correspond to patients which PK is shown in Figure 1. The lines are calculated using the fit parameters given in Table 1 and Equation 2 for the 2.5%, 50% and 97.5% quantiles. All except two individuals are within these limits. The vertical solid lines mark patients with creatinine clearances of 30 ml/min and 70 ml/min, curves stop at 150 ml/min.

A commonly used surrogate marker for actual creatinine clearance is the Cockcroft-Gault formula, which employs creatinine measurements and a patient s age and weight to predict the clearance. It is named after the scientists who first published the formula. The equation is popular because it is easy to calculate. 

It is difficult to obtain an accurate measure of renal function in patients with cirrhosis. A number of studies have shown that they tend to have low serum creatinine levels. This has been explained by a reduced muscle mass in cirrhotic patients and a reduced conversion of creatine to creatinine [10]. The calculation of creatinine clearance using the Cockcroft and Gault formula is also inaccurate in predicting GFR in these patients because it uses the serum creatinine level (which may be falsely low) and body weight in the calculation, which is likely to be inflated due to the presence of ascites [12]. The measured creatinine clearance, based on urinary excretion of creatinine, should theoretically be more accurate, even in patients with reduced muscle mass or impaired creatinine synthesis. However, it has been shown that this also overestimates the GFR because of an increased fractional tubular secretion of creatinine in cirrhotic patients, particularly those with reduced GFR [10]. 

The safety and efficacy of amphotericin colloidal dispersion have been evaluated in 148 immunocompromised patients with candidemia (20). ABCD was given intravenously in a median daily dose of 3.9 (range 0.1-9.1) mg/kg for a median of 12 (range 1-72) days. In the safety analysis (n = 148 patients), nephrotoxicity occurred in 16% of the patients, with either doubling of the baseline serum creatinine concentration or an increase of 88 pmol/l (1.0 mg/dl) or a 50% fall in calculated creatinine clearance. Severe adverse events were believed to be probably or possibly related to ABCD in 36 patients (24%), including chills and fever (9.5%), hypotension and abnormal kidney function (4%), tachycardia, asthma, hypotension (3%), and dyspnea (2%). ABCD was withdrawn in 12%... 

The safety and efficacy of ABCD have been stndied in 220 bone marrow transplant recipients enrolled in the same five phase I or phase II stndies (23). The median dose in this population was 4 (range 0.4—8.0) mg/kg, and the median duration of treatment was 16 (range 1-409) days. Overall, 37 (19%) of the patients had nephrotoxicity, defined as a doubling of serum creatinine from baseline, an increase of 88 pmol/l from baseline, or at least a 50% fall in calculated creatinine clearance. There were no significant changes in hepatic transaminases, alkaline phosphatase, or total bilirubin. Fever and chills were reported by 12 and 11% of patients respectively. Other acute, severe, infusion-related adverse events were hypoxia (4.1%), hypertension (2.7%), and hypotension (2.7%). 

Continuous infusion of amphotericin has been assessed in an open study in six lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections who were treated for 40 (17-73) days by 24-hour continuous infusions of amphotericin 1 mg/kg (113). They received at least 1000 ml/day of 0.9% saline intravenously. Apart from ciclosporin, five patients received aminoglycosides for at least 2 weeks, and four received ganciclovir. Calculated creatinine clearance fell from 57 (43-73) ml/minute to a nadir of 35 (28-39) and recovered to 52 (33-60) after the end of therapy. One patient needed temporary hemofiltration for 7 days. Besides three episodes of mild hypokalemia there were no adverse effects attributable to amphotericin. Asymptomatic colonization with Candida persisted for 10 months in one case, but the other five patients were cured. 

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