Relationship between serum creatinine, endogenous creatinine clearance and urinary creatinine.
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Biochemical Phenomena↗
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Plasma creatinine and creatinine clearance in nutritional osteomalacia.
To confirm recent observations that some vitamin D deficient osteomalacic patients had low plasma creatinine concentrations, low urinary creatinine excretion, and a paradoxically low creatinine clearance, and whether these changes were due to vitamin D deficiency per se, these measurements were made in patients before and after vitamin D supplementation. The pretreatment levels were also compared with those in healthy controls and in non-osteomalacic patients without renal disease. The above changes were confirmed. After treatment with vitamin D, plasma creatinine concentrations rose, but urinary creatinine excretion and creatinine clearance did not alter. These data indicate the limitation of creatinine clearance as an index of renal function in vegetarian osteomalacic patients. Furthermore, they demonstrate the effect of vitamin D deficiency and its reversal on plasma creatinine concentrations.
Bone and Bones↗
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↗
Effects of diet and antihypertensive therapy on creatinine clearance and serum creatinine concentration in the Modification of Diet in Renal Disease Study.
Factors other than the glomerular filtration rate (GFR) can affect creatinine clearance (Ccr) and serum creatinine concentration (Pcr). The effect of dietary protein and antihypertensive therapy on Ccr the reciprocal of the Pcr (1/Pcr). and their determinants (GFR, creatinine clearance from tubular secretion (CTScr), and creatinine excretion (UcrV) values) was assessed in patients participating in the Modification of Diet in Renal Disease (MDRD) Study. This study compared the effects of assignment to a low versus usual-protein diet and to a low versus usual-blood pressure goal on the decline in these measurements over 3 yr in 585 patients with baseline GFR of 25 to 55 mL/min per 1.73 m2 (Study A). This study also assessed correlations and associations of these measurements with each other and with protein intake, blood pressure, class of antihypertensive agents, and renal diagnosis in 840 patients with baseline GFR of 13 to 55 mL/min per 1.73 m2 (Studies A and B). In Study A, the estimated mean decline in GFR at 3 yr did not differ significantly between the low and usual-protein diet groups (-10.9 versus -12.1 mL/min). In contrast, CTScr declined more in the low-protein diet group (-7.8 versus -3.6 mL/min, P < .05). Consequently, the low-protein diet group had a greater decline in Ccr (-17.6 versus -14.4 mL/min, P < .05). The low-protein diet group also had a greater decline in UcrV (-306 versus -92 mg/day, P < .05). The decline in UcrV was proportionately greater than the decline in CTScr hence the decline in 1/Pcr was less in the low-protein diet group (-0.091 versus -0.122 dl/mg, P < .05). Similarly, in Study A, there was no significant difference in the decline in GFR at 3 yr between the low and usual-blood pressure groups (-10.7 versus -12.3 mL/ min). However, there was a lesser decline in CTScr in the low blood pressure group (-4.7 versus -6.7 mL/ min, P < .05). Consequently, the decline in Ccr was less in the low blood pressure group (-14.2 versus -17.8 mL/min, P < .05). There was no significant difference in UcrV between the blood pressure groups (-192 versus -205 mg/day). Hence, the decline in 1/Pcr paralleled the decline in Ccr; it was less in the low blood pressure group (-0.091 versus -0.122 dL/mg, P < .05). In Studies A and B, correlations of rates of decline in Ccr and GFR were 0.64 and 0.79, respectively (P < 0.001). Correlations of rates of decline in 1/Pcr and GFR were 0.79 and 0.85, respectively (P < 0.001). In Studies A and B combined, baseline GFR, CTScr and UcrV correlated significantly with protein intake (r = 0.45, 0.47, and 0.36, respectively; P < 0.001), but not with blood pressure. Baseline CTScr was significantly lower in patients with polycystic kidney disease and tubulointerstitial diseases or urinary tract diseases, compared with glomerular and other diseases (P < 0.05). It was also lower in patients who were taking calcium channel blockers, compared with patients not taking these agents, and in patients not taking diuretics, compared with patients taking diuretics (P < 0.05). These results show that creatinine secretion and excretion are affected by protein intake. Creatinine secretion is also affected by antihypertensive therapy and renal diagnosis. In the MDRD Study, the low-protein diet reduced creatinine secretion and excretion, and the low blood pressure goal slowed the decline in creatinine secretion. These effects caused differences between the diet groups and between the blood pressure groups in Ccr and 1/Pcr that were not the result of differences in GFR. Studies assessing the effects of these interventions on the progression of renal disease should measure GFR in addition to Ccr and Pcr.
Antihypertensive Agents↗
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↗
[Estimation of creatinine clearance by the height/plasma creatinine formula in critically-ill children].
INTRODUCTION: Critically-ill children frequently show impaired renal function, necessitating adjustment of drug dosages. Our objectives were to study estimated creatinine clearance through the correlation between the height/plasma creatinine formula (CrClest) and measured creatinine clearance (CrClms) and to examine whether CrClest over- or underestimates CrClms by analyzing the influence of diagnosis, severity, and the practical consequences. PATIENTS AND METHODS: Seventy-seven patients admitted to the pediatric intensive care unit were included. CrClms was calculated using serum creatinine and creatinine in urine collected over 24 hours. CrClest was estimated using serum creatinine, height, and a constant. The difference between CrClms and CrClest was expressed as a percentage: (CrClms CrClest) x 100/CrClms. Differences of greater than 15 % were considered poor estimates. ResultsThe mean percentage difference was 29.2 (standard error: 39.9). There were no differences among diagnoses in the distribution of significant bias, although the frequency of metabolic diagnoses was high. Incorrect evaluation of CrClest would result in a therapeutic error in 11.69 % of the cases, with overdosage in 10.39 %. The Pediatric Risk of Mortality (PRISM) score was higher (p < 0.05) in patients at risk for overdosage. CONCLUSIONS: CrClest estimation using the height/plasma creatinine formula was not an accurate method in critically ill children. In 10.39 % of patients with more severe illness, the dosage of renally excreted drugs would be too high. The highest risk was found in patients with metabolic and neurological diagnoses.
Adolescent↗
Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay.
BACKGROUND: Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to compare cimetidine-aided GFR estimations using various creatinine assays. METHODS: In 30 outpatients with NIDDM GFR was measured as the urinary clearance of continuously infused [125I]iothalamate. Plasma creatinine concentration was analysed after oral cimetidine with an alkaline picrate (AP) method, with an enzymatic (PAP) assay and with HPLC. GFR estimations were calculated with the Cockcroft Gault formula (CG). RESULTS: AP creatinine concentrations were significantly higher than PAP or HPLC values. GFR estimations by AP (CG(AP) 66 +/- 19 ml/min/1.73 m2, mean SD) were significantly lower than GFR (89 +/- 30), whereas CG(PAP) (85 +/- 30) and CG(HPLC) (84 +/- 34 ml/min/1.73 m2) were not. Bland and Altman analysis showed a difference between CG(AP) and GFR of -22.4 +/- 17.7 ml/min/1.73 m2; this difference becomes larger when the GFR increases. The difference between CG and GFR was only -3.8 +/- 14.8 ml/min/1.73 m2 for PAP and -4.4 +/- 17.5 ml/min/1.73 m2 for HPLC, without any systematic difference. CONCLUSION: A good assessment of the GFR from plasma creatinine after cimetidine administration is possible when creatinine is measured with an enzymatic assay or with the less convenient HPLC method. The more widespread and cheaper alkaline picrate assay is not suitable for GFR-estimation.
Adult↗
Decreased rate of creatinine production in patients with hepatic disease: implications for estimation of creatinine clearance.
Serum creatinine concentration is commonly used in conjunction with individual patient characteristics (e.g., age, sex, and body weight) in order to estimate creatinine clearance. Such estimates of creatinine clearance are widely used as a parameter for individualization of dosages of drugs excreted primarily via the kidneys in patients with diminished renal function. However, estimation of creatinine clearance in patients with concurrent hepatic disease tends to result in substantial overprediction of observed creatinine clearance in this patient population. This report suggests that a diminished rate of creatinine production in patients with hepatic disease is a likely explanation for this anomaly. This postulated mechanism is based on a presentation of the biology of creatinine formation.
Adult↗
Genomewide linkage analysis to serum creatinine, GFR, and creatinine clearance in a community-based population: the Framingham Heart Study.
Kidney disease is a risk factor for the development of cardiovascular disease, all-cause mortality, and ESRD. It is not known to what extent genetic factors play a role in the development of kidney disease in the general population. Multipoint variance components linkage analysis was performed using Genehunter on 330 families from the Framingham Heart Study offspring cohort, using a 10-cM genomewide scan for serum creatinine, GFR, and creatinine clearance (CRCL) measured from 1998 to 2001. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation, and CRCL was estimated using the Cockcroft-Gault equation. Covariates in the adjustment included age, gender, body mass index, diabetes, systolic BP, hypertension treatment, tobacco use, and HDL cholesterol. Overall, 1224 subjects (52% women), mean age 59, were available for analysis. Mean creatinine was 0.87 mg/dl, mean GFR was 87 ml/min per 1.73 m(2), and mean creatinine clearance was 100 ml/min. The multivariable-adjusted heritability estimates for creatinine, GFR, and CRCL were 0.29, 0.33, and 0.46, respectively. The peak log of the odds ratio (LOD) scores for serum creatinine, GFR, and CRCL were 2.28 at 176 cM on chromosome 4, 2.19 at 78 cM on chromosome 4, and 1.91 at 103 cM on chromosome 3, respectively. In a community-based sample, measures of serum creatinine, GFR, and CRCL are heritable, suggesting an underlying genetic component. These results also provide suggestive evidence for linkage to measures of kidney function. Further research is necessary to identify the genes involved in the development of kidney disease and to understand their roles in this complex process.
Adult↗
The influence of a cooked meat meal on creatinine plasma concentration and creatinine clearance.
1 The influence of a meal containing cooked meat (225 g) on creatinine plasma concentration, creatinine urinary excretion and creatinine clearance was determined in six healthy male subjects. 2 The meat meal produced an average 52% increase in creatinine plasma concentration within 1.5 to 3.5 h after ingestion. The 24 h area under the creatinine plasma concentration-time curve increased by about 19%. Urinary creatinine excretion during 24 h increased by an average of 13%. Creatinine clearance was not altered in response to the meal of cooked meat.
Adult↗
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↗
[Increase of tubular secretion of creatinine by L-arginine: mechanism of practical significance in the assessment of renal function based on creatinine clearance].
BACKGROUND: Tubular secretion of creatinine is increased by meat meals. This increment has been attributed to the formation of new creatinine from creatine contained in the cooked meals. However, no studies are available using amino acid infusions containing no creatine, which allow to further investigate the putative causes of increment in tubular creatinine secretion. METHODS: We performed a prospective, interventional study involving 34 individuals with normal renal function participating in a protocol on arterial hypertension. A continuous infusion of L-arginine (6%, i.v., in four 30 min periods at 50, 100, 200 and 300 ml/h) was administered. Creatinine (CCr) and inulin (CIn) clearances were determined at baseline and during L-arginine infusion. We analyzed the effects of L-arginine on tubular secretion by comparing CCr and CIn and calculated tubular secretion of creatinine (TSCr). RESULTS: L-arginine infusion induced a significant increase in both CCr and CIn. CCr and CIn were respectively 117.9 +/- 22.7 and 107.5 +/- 23, before and 170.3 +/- 23 and 144.2 +/- 47.8 after the infusion of L-arginine (both p < 0.01). This increase was simultaneous with an increment in TSCr from 1.12 +/- 0.4 to 1.43 +/- 0.6 (p < 0.01). CCr correlated significantly with CIn at baseline and at 60 min of infusion (r = 0.365, p = 0.031 and r = 0.368, p = 0.038, respectively), but not at 120 min (r = 0.130, p = 0.412), a time corresponding to the maximum increase in CIn and TSCr. CONCLUSIONS: L-arginine induces a substantial increase of CCr, which exceeds that expected from the increase in glomerular filtration rate measured by CIn and corresponds to an increment in TSCr. This phenomenon adds a new interpretation of the effect of amino acids on tubular handling of creatinine and has practical implications in the evaluation of renal function by means of creatinine clearance.
Adult↗