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A longitudinal study of urinary creatinine and creatinine clearance in normal subjects. Race, sex, and age differences.

The purpose of this study was to examine the variability of 24-hour urinary and serum creatinine levels and creatinine clearance in normal subjects and to develop nomograms for assessing the adequacy of 24-hour urine collections. The data were from a longitudinal research program examining biochemical, hormonal, and hemodynamic parameters in normal subjects. Bloods and 24-hour urine specimens were collected at yearly intervals from 144 people over 9 years, and from an additional 110 over 4 years. The subjects were originally distributed equally by sex, race (black, white), blood pressure (three groups within the normal range), and age (three groups). Men had 33% higher urine creatinines per weight than females (P less than 0.001). Because they only had 8% higher creatinine clearance per weight they also exhibited 21% higher serum creatinine. Blacks had 5% higher urine creatinine per weight than whites, perhaps reflecting greater muscle mass, but their serum creatinines were not different from those of whites, reflecting a 5% higher creatinine clearance by weight than whites (P less than 0.01). Interestingly, older black men (age greater than 60 years) had 12% lower urine creatinine/weight than younger black men (P less than 0.001). They also had 13% lower creatinine clearance by weight, resulting in no net difference in serum creatinine. The intraindividual variability in urine creatinine excretion averaged 15% and did not differ between blacks and whites and men and women. The within individual variability in serum creatinine and creatinine clearance averaged 14 and 20%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Biological variation of serum and urine creatinine and creatinine clearance: ramifications for interpretation of results and patient care.

Analytical and intra- and inter-individual components of variation were assessed over a 40-week period in 15 apparently healthy subjects, seven men and eight women, for serum creatinine, urine creatinine expressed in both concentration and output terms, and creatinine clearance, both uncorrected and corrected to standard surface area of 1.73 m2. Serum creatinine, even when considered separately for men and women, has marked individuality, and conventional population-based reference ranges are consequently of limited value. In contrast, urinary creatinine and creatinine clearance have less individuality, and reference ranges are more useful. Desirable analytical standards are not attained for serum creatinine assays, but are achieved for urine creatinine and clearance determinations. Creatinine clearance is, therefore, the favoured first-line test for initial assessment of patients. However, the small critical difference required for two serum creatinine results to be significantly different, and the comparatively large critical difference for clearance, make serial serum creatinine assays more useful for monitoring individuals.

Adult

Assessment of renal function by serum creatinine and creatinine clearance: glomerular filtration rate estimated by four procedures.

We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.

Adolescent

Estimation of renal creatinine clearance in patients with unstable serum creatinine concentrations: comparison of multiple methods.

The accuracy of different methods of calculating 24-hour creatinine clearance in patients with unstable renal function was compared using simulated data (based on a one-compartment pharmacokinetic model), as well as data from postrenal transplant patients. When creatinine clearance was calculated from the urinary creatinine excretion and a serum creatinine concentration, the use of the midpoint serum creatinine concentration produced the lowest degree of error. Therefore, this method is recommended for routine clinical determination of creatinine clearance in such patients. When the urinary creatinine excretion was unknown, an iteration method produced the lowest degree of error among four methods, and therefore is recommended to estimate creatinine clearance in such patients.

Adult

Specific creatinine determination in laboratory animals using the new enzymatic test kit "Creatinine-PAP".

The new Creatinine-PAP test kit from Boehringer Mannheim GmbH was evaluated for the determination of creatinine in dogs, rabbits, guinea pigs, rats, and mice. In comparison with methods based on the reaction with alkaline picrate, the enzymatic method gave the lowest serum creatinine values. The differences are caused by serum substances (non-creatinine chromogens) reacting with picric acid. Noticeable differences between the standard inulin clearance and creatinine clearance (e. g., in rats) arise because the non-creatinine chromogens interfere differently in the picric acid methods, and serum and urine contain different concentrations of interfering substances. The concentrations of non-creatinine chromogens are different in the various laboratory animals. Since these substances cannot be entirely removed (e. g., in rats, dogs) by the adsorption procedure with Fuller's earth, we recommend the peroxidase-coupled enzymatic test as a practical and specific method for routine measurements of creatinine in laboratory animals.

Animals

Creatinine clearance: enzymatic vs Jaffé determinations of creatinine in plasma and urine.

We measured creatinine in plasma and urine samples from 17 normal subjects and 10 renally impaired subjects by four different methods: two enzymatic--Ektachem iminohydrolase and Boehringer Mannheim amidohydrolase--and two Jaffé reaction based--Beckman Astra 8 and Technicon AutoAnalyzer I. Creatinine clearances, standardized for body surface area, were also calculated. In both groups of subjects plasma creatinine values were significantly (p less than 0.05) lower, by 3 to 4 mg/L, when measured enzymatically than when measured by the Jaffé reaction. Additionally, creatinine clearances were significantly (p less than 0.05) greater by at least 30 mL/min when calculated from enzymatically measured creatinine values vs Jaffé method values for creatinine. The benefits of lack of interference with enzymatically measured creatinine concentrations and clearances should be assessed in relation to the lack of agreement with long-established (Jaffé) methods for determining creatinine (and inulin) clearances.

Amidohydrolases

A method for determining the pharmacokinetics of endogenous creatinine without exogenous creatinine administration.

A method for determining the individual pharmacokinetics of endogenous creatinine is derived and applied in 10 post-renal transplant patients. All patients had rapidly decreasing serum creatinine concentrations (C), but relatively constant creatinine clearance (Clcr) during the study period. Based on the multiple consecutive Clcr and the corresponding C, the elimination rate constant (K), volume of distribution (V), and daily creatinine production rate (R) for each patient were derived. The creatinine 'normal' t1/2 (corresponding to a Clcr of 120 ml min-1) was also calculated. In the 10 patients studied, the observed Clcr ranged from 29.5 to 72.7 ml min-1. The corresponding calculated mean K was 0.076 +/- 0.028 h-1; R was 20.0 +/- 5.7 mg kg-1 day-1, and V was 0.60 +/- 0.1 1 kg-1. The 'normal' t1/2 was 4.0 +/- 0.93 h. These pharmacokinetic parameters are consistent with those derived from radiotracer studies and other methods reported in the literature. The present study shows that the individual endogenous creatinine pharmacokinetics can be determined by a relatively simple and noninvasive method in certain selected patients if the appropriate serum and urinary creatinine concentrations are obtained.

Creatinine

Factors influencing the production of creatinine: implications for the determination and interpretation of urinary creatinine and creatine in man.

The rates of creatine/creatinine inter-conversions and their equilibrium were studied under controlled conditions of temperature and pH that simulate urine storage conditions. The concentrations and ratios of creatine to creatinine in urine obtained from subjects with various pathophysiological conditions were determined, both before and after storage. The observed changes occurring during storage were compared with predicted changes based on observations of standard solutions. The initial reaction rate was found to increase with temperature, occurring maximally at about pH 3.7 for the conversion of creatine to creatinine, and at about pH 5.0 for the conversion of creatinine to creatine. At low pHs the equilibrium position was displaced towards creatinine. Above about pH 6.0 the equilibrium was associated with approximately equimolar quantities of creatine and creatinine. The creatine content of urine ranged from virtually nil to about double that of creatinine and changed predictably during storage. These findings have implications for the use of creatinine as an index of muscle mass and nutritional status, and as a marker for the completeness of urine collections.

Adult

Creatinine clearance estimation from serum creatinine values: an analysis of three mathematical models of glomerular function.

The logarithmic relationship of serum creatinine and creatinine clearance was analyzed in 100 adult patient studies using a geometric regression technique. Each sex was independently analyzed, and the subsequently derived regression formulae were age corrected resulting in mathematical models useful in estimating creatinine clearance from serum creatinine concentrations. These formulae were tested prospectively in another group of 100 patient studies in which creatinine clearance had been determined, and the results compared to values derived by use of two other published formulae. This newer method resulted in a closer distribution of data around a line of identity compared to other formulae and allowed for a good "bedside" estimation of creatinine clearance from serum creatinine concentration.

Adolescent

Creatinine clearance in the elderly: a comparison of direct measurement and calculation from serum creatinine.

In 53 patients, aged over 70 years and admitted as urgent cases, creatinine clearance was determined biochemically in 24-hour urine and serum. The adjusted creatinine clearance value was compared with the values obtained by the formulas of Cockcroft and Gault [Nephron 16: 31-41, 1976], Kampmann et al. [Acta med. scand. 196: 517-520, 1974] and Hallynck et al. [Clin. Pharmacol. Ther. 30: 414-421, 1981] where creatinine clearance can be estimated from the serum creatinine concentration. A significant connection was found between the adjusted creatinine clearance and the values by the formula of Cockcroft and Gault (r = +0.46), compared with the formula of Kampmann et al. (r = +0.53), although only a small correlation was seen in comparison with the formula of Hallynck et al. (r = +0.30). A very high correlation of the obtained values was found by the formulas of Cockcroft and Gault and Kampmann et al. (r = +0.99) and also a significant correlation with the formula of Hallynck et al., (r = +0.56). By comparing the values according to formulas of Kampmann et al. and Hallynck et al. a significant connection was obtained (r = +0.59). The method of Cockcroft and Gault could be used as a fast analysis of creatinine clearance in older patients with great individual variation, as could the formula of Kampmann et al., but the determination of creatinine clearance by a biochemical method is a reliable reference.

Aged

Reference values of serum and urine creatinine, and of creatinine clearance by a new enzymatic method.

A new, totally enzymatic procedure for the determination of creatinine in serum and urine, using creatinine amidohydrolase, creatine amidinohydrolase, sarcosine oxidase and formaldehyde dehydrogenase is described. The assay was adapted to a discontinuous analyser with each analysis requiring only 20 microL of serum or 3 microL of urine. Analytical recovery of creatinine in serum and urine averaged 100.6%. Within-run and between-run precision studies gave coefficients of variation of 1.1% and 1.8%, respectively, for a serum with mean values of 83 mumol/L (9.4 mg/L) creatinine. Creatinine concentrations in serum and urine were measured by this procedure, in Japanese children and adults. The reference intervals for serum creatinine concentrations in adults were 55-96 mumol/L (6.2-10.9 mg/L) in men and 40-66 mumol/L (4.5-7.5 mg/L) in women, and for urine, 9.46-19.01 mmol/day (1070-2150 mg/day) in men and 6.75-10.61 mmol/day (764-1200 mg/day) in women. The reference intervals of creatinine clearance were 88.0-176.4 mL/min in men and 75.7-173.0 mL/min in women.

Adult

Influence of endogenous and exogenous Jaffé-reaction-positive pseudo-creatinine chromogens in determination of creatinine in blood of normal and cephaloridine-administered rats.

To investigate a magnitude of analytic errors brought by certain interfering substances to the chemical method using Jaffé-reaction for determination of creatinine, two sorts of values determined by the chemical method and by the HPLC method were compared between each other, in blood samples obtained from control and cephaloridine (CER)-administered rats. The rats that received an intravenous injection of CER in dose of 1,000 mg/kg body weight, showed two peaks at the 1-hour and on the 3-day. Since the color development of CER determined in the chemical method showed that 1 g of CER corresponded to 0.0208 g of creatinine, the results of plasma CER determination proved that the first peak was ascribable to the color development of CER. As to the second peak, no significant difference was observed between the values of the two methods. This finding denoted that, when the creatinine levels were elevated, the two sorts of values due to the two methods approached to one another, and suggested that the ratio of "endogenous Jaffé-reaction-positive pseudo-creatinine chromogens" to "total Jaffé-reaction-positive chromogens" would be decreased according as the "true" creatinine was increased. In the control rats, the ratio to "total Jaffé-reaction-positive chromogens" was 60% in terms of "true" creatinine, and 40% in terms of "endogenous Jaffé-reaction-positive pseudo-creatinine chromogens."

Animals

[Plasma creatinine, and clearance and urinary excretion of creatinine in children].

The 24 hour clearance of endogenous creatinine was compared with that of inulin in 112 children aged between 15 months and 17 years. The children had a variety of kidney disorders with renal function than ranged from normal to terminal renal failure. When the inulin clearance was less than 10 ml/min/1.73 m2 it was on average 75% of the value of the creatinine clearance. Between 10 and 60 ml/min/1.73 m2 the relationship of the inulin clearance to that of creatinine was similar (77%) but above 60 ml/min/1.73 m2 the ratio of the inulin clearance to that of creatinine was 1.05 with a wide scatter. With increasing degrees of renal failure the plasma creatinine increased less in the children under 2 years old than in those over this age so it is poor index of glomerular function in infants. In renal failure the urinary excretion of creatinine in 24 hours was reduced. When the clearance was less than 10 ml/min/1.73 m2, the urinary creatinine excretion for children under the age of 2 was 58% of the normal for the age and for children over 2, it was 86% of the expected mean.

Adolescent

Creatinine deiminase (EC 3.5.4.21) from bacterium BN11: purification, properties and applicability in a serum/urine creatinine assay.

Creatinine deiminase (EC 3.5.4.21) from the anaerobic microorganism BN11 has been purified to homogeneity by ammonium sulfate fractionation, gel filtration on Sephacryl-S-300 superfine and chromatography on DEAE-Sepharose C1 6B. The final enzyme preparation had a specific activity of 78 units per mg protein. Analysis of creatinine deiminase by polyacrylamide gradient gel electrophoresis and fast-flow-liquid-chromatography gave a relative molecular mass of 285 kDa and 288 kDa, respectively. By treatment with sodium dodecylsulfate and 2-mercaptoethanol creatinine deiminase was dissociated yielding one polypeptide with a relative molecular mass of 47.5 kDa. The enzyme was entirely specific for creatinine and showed a Km value of 0.15 mM. Creatinine deiminase was used to determine the concentration of creatinine in serum and urine using a manual method and an automated system.

Aminohydrolases

Correlation between measured creatinine clearance and calculated creatinine clearance in ovarian cancer patients.

In 84 patients with advanced ovarian cancer, the measured 24-hr urinary creatinine clearance and a calculated creatinine clearance were compared prior to cis-platinum-based chemotherapy. The overall correlation between the two methods was excellent, using Pearson's coefficient of correlation test, r = 0.508 and P less than 0.000001. In a subset of 59 patients with adequate 24-hr urine collections, analysis showed a correlation of r = 0.526 and P = 0.000018. Furthermore, in this group of patients using a creatinine clearance of 45 ml/min as a threshold for dose adjustment, there was only a 3.3% error in accepting the calculated creatinine clearance for the measured creatinine clearance. In summary, in patients with advanced ovarian cancer, even in the postoperative state, an evaluation of renal function with a calculated creatinine clearance prior to chemotherapy is sufficient.

Adult

[Serum creatinine and endogenous creatinine clearance].

It is reported on the clinical evidence of the determination of creatinine and of the endogenic creatinine clearance. The determination of the serum creatinine gives a good parameter for the observation of the course in advanced renal insufficiency. The endogenic creatinine clearance which is often carried out in the clinical practice in the normal and moderately limited region allows in most cases sufficient measurement of the filtrate of the glomerulum. On 118 in-patients a method was tested which allows a nomographic estimation of the endogenic creatinine clearance on the basis of the actual serum creatinine level, taking into consideration age, sex, and bodyweight.

Age Factors

A study of urinary creatinine and creatinine coefficient in healthy young adults.

Daily urinary creatinine excretion and creatinine coefficient of eighty-four healthy medical students have been studied for three consecutive days. Daily creatinine excretion has been observed to be higher in the male subjects compared to the female counterparts. Creatinine excretion has been observed to be dependent on body weight of the subjects. The variability from subject to subject was higher than observed by most other workers. Day to day consistency within the same subject was rather low. Creatinine coefficient was computed per kg of body weight as well as per kg of lean body weight. In both the cases, it has been found to be higher in the males than in the females. Though an important factor, yet body weight of a subject alone could not explain satisfactorily wide variability of creatinine excretion in the present study. The possible influencing factors have been discussed along with clinical implications.

Adolescent

Protein: creatinine and trypsin inhibitor: creatinine ratios in the urine of marathon runners.

We measured changes in the protein: creatinine and trypsin inhibitor: creatinine ratios in the urine of six male marathon runners. Samples of urine were collected before the run, immediately after the run and in 6-h collections for 2 days. We found the greatest increase in the protein: creatinine ratio (2.6 times greater) in urine collected immediately after the run and the greatest increase in the trypsin inhibitor: creatinine ratio in urine samples collected 6-12 and 12-18 h after the run (2 and 3 times greater, respectively). This suggests the existence of different mechanisms for these two physiological processes. The later increase in the trypsin inhibitor: creatinine ratio was perhaps, due to a state of short-lived inflamation and shock after severe physical effort.

Adult