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Creatinine clearance estimation from serum creatinine values: evaluation and comparison of five prediction formulae in Nigerian patients.

Predictability of creatinine clearance (CrCl) from serum creatinine would reduce the cost of renal care and obviate the need for 24-hours urine collection. Correlations have been established between serum creatinine (Scr) and 24-hour urinary creatinine clearance with derivation of various formulae. We have tested the applicability of these formulae in 34 Nigerian patients (22 males, 12 females) aged 18 to 58 years, (mean age 34.97 +/- 11.20 years) with established chronic renal failure (CRF) mean Scr level 742.26 +/- 388.15 mol/L. 32 age and sex matched healthy adults with serum creatinine values below 120 umol/l., served as controls. Serum creatinine and 24 hour CrCl levels were determined on two consecutive occasions. Creatinine clearance values were also derived from Scr using each of the established prediction formulae: Cockcrof and Gault [1] Gates [2] Hull et al [3]; Jelliffe [4]; and Mawer et al [5]. A relationship was sought between measured CrCl and the predicted values (derived) using the stated formulae. Regression equation were generated and correlation coefficient r, coefficient of determination r2, F-ration, prediction error, all defining the nature and strength of relationship were determined. We observed that good and statistically significant correlations exist between measured CrCl values and those predicated from the formulae (r ranging from 0.908 to 0.968 and r20.82 to 0.93 P = 0.000) and that a linear relationship exists in all cases. Cockcroft and Gault formula gave the highest coefficient of determination r2 = 0.94. It is concluded that the existing formulae are adequate for determining CrCl from Scr and should be frequently used in the long term follow-up of patients with Chronic Renal Failure (CRF) in our setting.

Adolescent↗

Serum creatinine and prediction formulae for creatinine clearance.

Three formulae which could predict creatinine clearance from serum creatinine values were derived from the data which were obtained from the study of 169 patients and healthy control subjects. Values for creatinine clearance which were obtained by using these three formulae and four other previous formulae were compared with the observed values. Most of the predicted and observed values differed by more than 20% of the observed values. When a formula which was derived by using the data from forty-five healthy control subjects was used to predict the creatinine clearance values of this group and the patients, there was a close agreement between the observed and the predicted values for only the healthy control subjects but not the patients. Because of the various factors which affect creatinine excretion in health and disease, a predictive formula which includes serum creatinine alone and not urinary creatinine might give unreliable values.

Adult↗

[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↗

Levels of serum creatinine and estimated creatinine clearance over the age of 75: a study of an elderly Swedish population.

Serum creatinine was measured and creatinine clearance estimated using the Cockcroft-Gault (C-G) formula, in elderly people participating in a population study of the elderly, the Kungsholmen Project. This is an ongoing longitudinal study which was begun in 1987 and comprised all people in a district of Stockholm, born in 1912 or earlier. Out of 2368 people 1810 participated. In 1362 cases, serum creatinine and an estimation of the creatinine clearance could be obtained. The mean age of these elderly people was 81 years, and 92% were living in their own homes. A linear regression model showed that the weight of the elderly decreased by age, indicating a decrease in muscle mass. However, this was not accompanied by a decrease in serum creatinine levels. When creatinine clearance was estimated using the C-G formula, a significant decline with age was seen at an average rate of 1.2 ml/min per year. It declined from 52 ml/min at age 75 to 27 ml/min at age 95. The mean for the whole study group was 44.6 ml/min. Our data suggest that the glomerular filtration rate may be very low in the oldest old and that there is a continuing decline with increasing age, even in a population where a high number of the elderly are still living in their own homes. Furthermore, the lack of major changes in serum creatinine levels with age supports the idea that this parameter is not a reliable measure of renal function in the elderly.

Journal Article↗

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↗

Amperometric flow-injection analysis of creatinine based on immobilized creatinine deiminase, leucine dehydrogenase and L-amino acid oxidase.

Leucine dehydrogenase/L-amino acid oxidase was proposed as an enzymatic conversion system for ammonia and its application to amperometric assay of creatinine was investigated. Ammonia formed by creatinine deiminase catalyzed hydrolysis of creatinine was converted to L-leucine by leucine dehydrogenase, and the oxidation of L-leucine by L-amino acid oxidase was detected with an oxygen electrode. Two approaches were proposed to overcome the problem of endogenous ammonia and L-amino acids. The first was using glutamate dehydrogenase prereactor to remove endogenous ammonia; endogenous L-amino acids were corrected by a separate run. In the second approach, endogenous ammonia and L-amino acids were simultaneously compensated with a two-channel system. It resulted in double peak recording that the flow was split and rejoined between the two ends of creatinine deiminase reactor and a delay coil and a reference column were properly set at one of the two-channels. One gave the sum response of all responsible compounds, the other that of endogenous interferences except creatinine. Both approaches were applied to creatinine assay in urine and the results showed a good agreement with those obtained from the Jaffe method.

Amino Acid Oxidoreductases↗

The measurement of creatinine: a comparison between the Beckman Creatinine Analyzer II and the Selective Analyzer GSA IID.

The measurement of creatinine by two Jaffé-based procedures is described. In comparing the Beckman Creatinine Analyzer II and the Greiner Selective Analyzer GSA IID, better between-day precision was observed with the former. Percentage recovery of creatinine added to serum was quantitative for the Beckman Creatinine Analyzer II and 92-95% for the Greiner Selective Analyzer. The Greiner Selective Analyzer employs a serum blank and for this reason interference produced by pseudo-Jaffé chromogens in the measurement of creatinine was far less significant than the corresponding interferences observed with the Beckman Creatinine Analyzer II. Comparison of results obtained on 100 sera and 40 urine samples provided correlation coefficients of 0.998 and 0.997 respectively.

Chemical Phenomena↗

Ketone interference in estimation of urinary creatinine; effect on creatinine clearance in diabetic ketoacidosis.

Acetoacetate is known to spuriously raise serum creatinine concentration in patients with diabetic ketoacidosis. Its effect on urinary creatinine has not been studied. Since the renal threshold for ketoacids is low, large amounts of acetoacetate may be present in the urine of uncontrolled diabetics. We investigated this interference using three different automated analysers. We found that +3 or +4 reactions with Ketostix, equivalent to greater than 10 - 15 mmol/L of acetoacetate caused significant interference with the Abbott VP and Beckman Astra instruments. This could cause errors in the calculation of creatinine clearance especially when serum creatinine is close to a normal level. We recommend that measurement of creatinine clearance be delayed until better diabetic control is achieved or the creatinine be measured by a method which is free from ketone interference, e.g., by the Dupont aca.

Acetoacetates↗

Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia.

BACKGROUND: The capacity to increase the tubular secretion of creatinine (TS(cr)) after an intravenous creatinine load (stimulated TS(cr)) has been found to be impaired in subclinical reduction of renal mass. We decided to investigate if this response was impaired in sickle cell anaemia (SCA) patients before there was evidence of deterioration of renal function. METHODS: Studies were done in 16 patients with homozygous SCA who had normal or supranormal glomerular filtration rate (GFR) and in 20 normal controls of similar median age (23 years). The tubular stress test (TST) consisted of 30-min clearance periods ([(125)I]iothalamate and creatinine) done before (baseline) and after (three successive post-stimulation periods) the intravenous infusion of 88.4 micromol (10 mg) of creatinine per kg of body weight. RESULTS: Baseline studies showed that the SCA patients had higher GFR and lower serum creatinine concentration. After stimulation there were no changes in GFR. In contrast, creatinine clearance increased 2.3 times in normal but not in SCA patients (P<0.001) and the TS(cr) in the first post-stimulation period was 161+/-83 nmol/kg/min in SCA patients vs 286+/-93.2 in normal controls (P<0.001). The mean TS(cr) post-stimulation was also reduced in patients with SCA (123+/-52 nmol/kg/min vs 179+/-50 in normal controls, P<0.001). Since SCA patients had lower P(cr) values, separate analysis was made of post-load clearance periods in which P(cr) was comparable in patients and in normal controls (range 177-265 micromol/l or 2-3 mg/dl) and the reduction in TS(cr) was also present in SCA patients in these study periods. CONCLUSION: Patients with SCA have impaired response to the TST before there are reductions in glomerular filtration. Therefore, a reduction in the tubular secretory reserve capacity represents an early event in the nephropathy of this condition.

Adolescent↗

Conventional measurement of renal function utilizing serum creatinine, creatinine clearance, inulin and para-aminohippuric acid clearance.

Inulin and para-aminohippuric acid clearances, determined by the conventional method of continuous intravenous infusion with blood and urine sample collections, are the gold standards for estimating glomerular filtration rate and renal plasma flow, respectively. Creatinine clearance provides a reasonably good estimate of glomerular filtration rate but is still subject to errors in accuracy and precision. However, novel methods employing cimetidine to block renal tubular creatinine secretion hold promise for improving the accuracy of estimates. More importantly, a large (and growing) number of studies have consistently demonstrated that estimating glomerular filtration rate by creatinine clearance calculated from the Cockcroft-Gault formula is better than measuring creatinine clearance with a 24-h urine collection. Until newer, more simple methods are developed, calculating creatinine clearance using fasting serum creatinine level, body weight, age and sex provides a reasonable and clinically useful bedside measure of glomerular filtration rate for the practising clinician.

Creatinine↗

Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance.

Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range. Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68-118 mumol/L, 58-120 ml/min/1.73 m2 and 0.51-0.98 mg/L, respectively. For women, the intervals were 68-98 mumol/L, 60-119 ml/min/1.73 m2 and 0.49-0.94 mg/L; for men, they were 78-123 mumol/L, 57-122 ml/min/1.73 m2 and 0.56-0.98 mg/L. This mean 95% reference interval for cystatin C in all donors under 50 years of age was 0.53-0.92 mg/L; for those over 50 years of age it was 0.58-1.02 mg/L. The small difference between make and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area. Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.

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↗

Enzymic assay of creatinine in serum and urine with creatinine iminohydrolase and glutamate dehydrogenase.

We describe an assay for creatinine in which it is converted by creatinine iminohydrolase (EC 3.5.4.21) into ammonia and N-methylhydantoin. The ammonia is subsequently assayed by use of alpha-ketoglutarate and glutamate dehydrogenase (EC 1.4.1.3). Use of NADPH as coenzyme eliminates all interferences from endogenous reactions. Endogenous ammonia in the sample is eliminated during a preincubation. The reaction reaches the endpoint in 15 min at working temperatures of 20-37 degrees C. No sample blank or reagent blank is needed. The standard curve is linear at least to 884 mumol (100 mg) of creatinine per liter. Average analytical recovery of creatinine in serum and urine is 99%. Within-run and between-run CVs are less than or equal to 2% and less than or equal to 6% for creatinine values of 335 mumol/L (38 mg/L) and 80 mumol/L (0 mg/L), respectively. Results by the described method (y) compare well with those by Jaffé's kinetic test (y = 1.01x -- 12.8), Berthelot/AutoAnalyzer method after treatment with immobilized creatinine iminohydrolase (y = 0.987x -- 13.2), Jaffé's test run on the SMA 12/60 (y = 1.011x -- 5.8), the Wahlefeld method (y = 1.014x -- 0.88), and Jaffé's test after deproteinization and absorption on fuller's earth (y = 0.985x -- 3.08). The method may be suitable for discrete, including centrifugal, automation.

Aminohydrolases↗

Creatinine X--potential nonrenal elimination of endogenous creatinine in humans and its clinical significance.

From an analysis of the data in the literature for creatinine renal clearance and steady-state serum level and published equations, we estimated a wide range (1.4-76.3 ml/min) of nonrenal clearances of endogenous creatinine. Nonrenal clearance might contribute 0-34% of the total body clearance in patients with normal renal function. This paper discusses the clinical significance of the potential overestimation of renal function by using published nomograms or equations (derived from a direct inverse relationship between the creatinine clearance and steady-state level or the assumption of nonexistence of nonrenal elimination of creatinine) for indirect estimation of creatinine clearances from serum creatinine levels.

Creatinine↗

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↗

Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis.

BACKGROUND: Several studies carried out in a limited number of patients demonstrated a wide range of overestimation of glomerular filtration rate (GFR) by serum creatinine level and creatinine clearance (Ccr) in liver disease. METHODS: We simultaneously evaluated Ccr, inulin clearance, and predicted GFR calculated from serum creatinine level in 56 cirrhotic patients. Inulin clearance was considered the gold standard for GFR evaluation. RESULTS: The sensitivity of serum creatinine level, predicted GFR, and Ccr in detecting renal failure was 18.5%, 51%, and 74%, respectively. On the basis of inulin clearance, patients were divided into two groups: those with normal GFR (mean, 106 +/- 34 mL/min per 1.73 m2) (group 1, 29 patients) and those with reduced GFR (mean, 56 +/- 19 mL/min per 1.73 m2) (group 2, 27 patients). Predicted GFR and Ccr were accurate markers of GFR in group 1 patients, while both overestimated GFR by about 50% in group 2 patients. An increased tubular secretion of creatinine accounted for the disparity between Ccr and inulin clearance in these patients. CONCLUSIONS: Our results indicate that renal failure is greatly underestimated on the basis of serum creatinine level and Ccr in cirrhotic patients. Clinical implications of this observation include excessive dosage of potentially nephrotoxic drugs and failure to recognize renal impairment induced by such medical treatments as diuretic therapy or paracentesis.

Adult↗