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Serum creatinine concentration, urinary creatinine excretion and creatinine clearance during the first 9 weeks in preterm infants with a birth weight below 1500 g.

UNLABELLED: Little is known about serum creatinine concentration, urinary creatinine excretion and creatinine clearance in preterm infants. The aim of the present study was to establish age related reference values for the first weeks of life in preterm infants with a birth weight < 1500 g. In addition, the possible influence of therapy with dexamethasone, spironolactone and catecholamines was investigated. In 34 patients, serum creatinine, urinary creatinine excretion and creatinine clearance were measured at weeks 1, 2, 3,-4, 5-6 and 7-9 of life. Median birth weight was 1225 g (range 730-1495), mean gestational age 29 (range 26-34) weeks. Concentration of creatinine in serum and urine, urinary creatinine excretion per kilogram body weight and creatinine clearance showed a significant correlation with postnatal age. Thus age related reference values as proposed given in the present study are desirable. Median serum creatinine concentration decreased continuously within the first weeks of life: 97 (10-90th percentile: 69-141) in the 1st week, 70 (45-99) in the 2nd week, 57 (39-71) at week 3-4, 51 (42-62) at week 5-6 and 44 (39-48) mumol/l at week 7-9. Median creatinine output in mumol/kg body weight was 100 (10-90th percentile: 62-160) in the 1st week, 92 (65-120) in the 2nd week, 79 (52-122) at week 3-4, 89 (68-106) at week 5-6 and 86 54-109) mumol/kg/d at week 7-9. Creatinine clearance increased significantly within the first weeks of life. Values were 12.5 (10-90 the percentile: 7-22) in the 1st week, 16 (10-28) in the 2nd week, 20 (11-34) at weeks 3-4, 23 (15-36) at weeks 5-6 and 29 (17-36) ml/min per 1.73 m2 at weeks 7-9. Therapy with dexamethasone, spironolactone or catecholamines showed no influence on creatinine excretion. Creatinine clearance did not only depend on postnatal age but also on gestational age and on the necessity of mechanical ventilation. These findings indicate a reduced glomerular filtration rate in very mature and severely ill preterm infants. CONCLUSION: It might be necessary to lower dosage of renal excreted drugs in very immature and mechanically ventilated infants according to the creatinine clearance.

Age Factors↗

Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffé method.

OBJECTIVES: The aim of this study was to determine the reference intervals for serum creatinine, the renal creatinine output and the creatinine clearance (CrCl) with two new methods for accurate creatinine determination. METHODS: The reference population consisted of 252 healthy subjects (127 males and 125 females) at the age between 18 and 74 years, median 27. Urine was collected for exactly 24 h. Creatinine in serum and urine was measured with an enzymatic assay ("Creatinine Plus") and a modification of the kinetic Jaffé reaction, named "Jaffé compensated". RESULTS: Reference values for serum creatinine were almost identical to previously published ones obtained with the same methods: 0.73-1.18 and 0.55-1.02 mg/dl for males and females, respectively, with the enzymatic, 0.72-1.16 and 0.55-0.96 mg/dl with the compensated Jaffé method (Jcomp). CrCl values were normally distributed and showed no gender difference in contrast to some previous studies. The reference interval for the entire group was found to be 66-143 ml/min with the enzymatic assay and 71-151 ml/min with the chemical one.

Adolescent↗

Serum creatinine and estimated creatinine clearance do not predict perioperatively measured creatinine clearance in neonates undergoing congenital heart surgery.

OBJECTIVE: To describe changes in creatinine clearance (CrCl) in a small group of neonates who underwent surgery for repair of transposition of the great arteries or palliation of hypoplastic left heart syndrome. To determine whether serum creatinine, urine output, or the Schwartz formula accurately predict measured CrCl in these patients. DESIGN: Prospective, randomized controlled trial with subsequent extraction of information regarding renal function from the database. SETTING: A 14-bed pediatric intensive care unit in a children's hospital. PATIENTS: A total of 14 neonates (hypoplastic left heart syndrome, 6; transposition of the great arteries, 8). MEASUREMENTS: Demographic information, urine output, serum creatinine, and 24-hr CrCl preoperatively and postoperatively on days 1 and 2. MAIN RESULTS: Weight, age, and body surface area were 3.3 +/- 0.6 kg, 8.2 +/- 6.9 days, and 0.2 +/- 0.02 m2, respectively. Urine output increased from 1.8 +/- 0.5 mL x kg(-1) x hr(-1) preoperatively to 2.4 +/- 0.8 mL x kg(-1) x hr(-1) on postoperative day 1 (p = .02) and 2.8 +/- 1.1 mL x kg(-1) x hr(-1) on postoperative day 2 (p = .007). Serum creatinine changed from 0.64 +/- 0.15 mg/dL preoperatively to 0.72 +/- 0.40 mg/dL on postoperative day 1 (p = .4, not significant) to 0.78 +/- 0.41 mg/dL on postoperative day 2 (p = .17, not significant). Measured CrCl changed from 22.8 +/- 9.4 mL x min(-1) x 1.73 m(-2) preoperatively to 25.1 +/- 31 mL x min(-1) x 1.73 m(-2) on postoperative day 1 (p = .77, not significant) and 24.9 +/- 19.9 on postoperative day 2 (p = .69, not significant). No difference in measured CrCl was noted based on hypoplastic left heart syndrome vs. transposition of the great arteries. Median overestimation of CrCl by the Schwartz equation was 58% preoperatively, 78% on postoperative day 1, and 53% on postoperative day 2. Clinically significant correlations were not noted between measured CrCl and serum creatinine or urine production preoperatively, on postoperative day 1, or on postoperative day 2. Bland-Altman plot demonstrated that the Schwartz equation was a biased and imprecise estimate of CrCl at all three time points. CONCLUSIONS: Perioperative CrCl is unpredictable in neonates with transposition of the great arteries and hypoplastic left heart syndrome. Serum creatinine, urine output, and the Schwartz formula do not accurately predict CrCl. Reliance on estimates of CrCl could result in toxic concentrations of drugs eliminated by the kidneys.

Cardiopulmonary Bypass↗

Correlation between serum creatinine, creatinine clearance, the calculated creatinine clearance and the glomerular filtration rate in heart transplant patients.

Assessment of glomerular filtration rate (GFR) in heart transplant (HTx) patients is based on serum creatinine (sCr), the endogenous creatinine clearance (C(Cr)) and radionuclide GFR (rGFR); however, the latter is expensive and time consuming. We reviewed the data of 32 adult HTx patients to determine the correlation between sCr, C(Cr), the calculated C(Cr) (Calc.C(Cr); based on gender, age, weight and sCr) and rGFR in long-term (>1 year) HTx patients receiving calcineurin inhibitors. The Calc.C(Cr) was found to have the best correlation with rGFR (r(2) = 0.65), followed by C(Cr) (r(2) = 0.53) and sCr (r(2) = 0.38). The use of Calc.C(Cr) to estimate GFR may be cost-effective in assessing renal function after HTx.

Aged↗

Modification of creatinine clearance by estimation of residual urinary creatinine and urea clearance in CAPD patients.

The use of creatinine clearance for adequacy of continuous ambulatory peritoneal dialysis (CAPD) requires consideration of the fact that a significant fraction of residual renal creatinine clearance is contributed by tubular secretion. We analyzed 123 peritoneal dialysis (PD) patients and corrected the residual renal creatinine clearance by averaging renal creatinine and urea clearance to estimate the glomerular filtration rate (GFR). Modified total creatinine clearance (peritoneal plus estimated renal GFR) was compared with total creatinine clearance (peritoneal plus total renal creatinine clearance). Modified and total creatinine clearances were not significantly different in patients with a total creatinine clearance less than 60 L/week/1.73 m2 body surface area (BSA), but a significantly lower modified total creatinine clearance was seen with patients having greater than 60 L/week/1.73 m2 BSA of total creatinine clearance. The correlation was better between KT/V and modified total creatinine clearance (r = 0.74) as compared to KT/V and total creatinine clearance (r = 0.67). We suggest that if creatinine clearance is used for peritoneal dialysis (PD) adequacy, the contribution of residual renal function should be calculated as the average of renal creatinine and urea clearance, thus estimating creatinine clearance only by the GFR. Further long-term studies are needed to confirm that modification of total creatinine clearance will better predict clinical outcome.

Creatinine↗

Assay of creatinine using the peroxidase activity of copper-creatinine complexes.

OBJECTIVES: It was our goal to develop a urine dipstick that could measure creatinine with a peroxidase reaction. The simultaneous measurement of albumin and creatinine permits the estimation of the 24-h albumin excretion, an important value in judging existing or likely development of renal failure. A highly sensitive dye-binding dipstick method for albumin exists, and a suitable dipstick for the assay for urine creatinine is described here. METHODS: Copper-creatinine and iron-creatinine complexes have peroxidase activity. With 3,3',5,5'-tetramethylbenzidine (TMB), and diisopropyl benzene dihydroperoxide (DBDH); the peroxidase activity of copper-creatinine and iron-creatinine complexes can be demonstrated. This reaction was used in the assay of urine creatinine either in solution or by a suitably impregnated urine dipstick. RESULTS: Our method based on the peroxidase activity of the copper-creatinine complex has an analytical range for creatinine of 100 mg/L (0.884 mmol/L) to 3000 mg/L (26.52 mmol/L). The creatinine assay is free from most interfering compounds that may be present in urine. Hemoglobin is an interferent, and its effects can be reduced but not eliminated by the addition of 4-hydroxy-2-methyl quinoline. We do not recommend using the dipsticks when visible blood is present or if the dipstick blood test is positive. The copper-creatinine complex oxidizes ascorbic acid; however, we were able to modify the reaction conditions so that ascorbic acid at < 4.4 g/L does not interfere. We found good agreement on fresh urines between the creatinine dipstick results and those by a standard rate-Jaffe cuvet method for creatinine. DISCUSSION: With the simultaneous measurement of creatinine and albumin in urine, the albumin/creatinine ratio can be determined effectively reducing or eliminating the occasional false-negative and false-positive result in those with dilute or concentrated urines, respectively. The dipstick test for these analytes permits the simple identification of individuals with possible albuminuria and could serve well in a point-of-care setting.

Amino Acids↗

Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine.

AIMS: To assess whether cystatin C, a new serum marker of renal function, is a better index of creatinine or digoxin clearance than serum creatinine in older people. METHODS: Twenty-two volunteers over the age of 65 years (mean 73 +/- 5) were recruited from a healthy elderly volunteer database. None of the volunteers was taking digoxin or other medication known to interfere with digoxin kinetics or assay. Digoxin was infused at a dose of 7-10 microg kg(-1) and blood samples were taken over the following 48 h and assayed for serum digoxin. Serum cystatin C, creatinine and creatinine clearance were measured and a calculated creatinine clearance was estimated using the Cockcroft Gault formula. Digoxin clearance was calculated using a pharmacokinetic software package. All values were log transformed to normalize their distribution. RESULTS: Of the 22 volunteers enrolled into the study, 18 completed the study. Serum cystatin C ranged between 0.72 and 1.89 mg l(-1) and serum creatinine ranged from 69.6 to 153.9 micromol l(-1). Measured creatinine clearance ranged from 38 to 123 ml min(-1) and calculated creatinine clearance from 29.5 to 88.0 ml min(-1). Digoxin clearance ranged from 51.0 to 103.5 ml min(-1). Cystatin C correlated extremely well with creatinine (r=0.93, P<0.001, 95% CI 0.82, 0.97) and with creatinine clearance (r=0.67, P=0.002, 95% CI 0.3, 0.87). Neither serum cystatin C nor serum creatinine correlated with digoxin clearance (r=0.25, P=0.31, 95% CI -0.25, 0.64 and r=0.44, P=0.068, 95% CI -0.03, 0.75, respectively). Measured creatinine clearance, however, did correlate well with digoxin clearance (r=0.55, P=0.018, 95% CI 0.11, 0.81). CONCLUSIONS: Serum cystatin C and serum creatinine show very similar correlations with creatinine and digoxin clearances. Serum cystatin C does not offer any advantages in this respect. It remains to be seen whether cystatin C offers any advantage over creatinine in elderly people in other respects.

Aged↗

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↗

Creatinine clearance but not serum creatinine alone predicts long-term postoperative survival after lower extremity revascularization.

BACKGROUND: Renal insufficiency is a well-described risk factor for perioperative morbidity and shortened survival after major vascular procedures. Due to the potential inaccuracy of serum creatinine levels alone in measuring kidney function, our aim was to determine whether estimated creatinine clearance more consistently predicted long-term survival. METHODS: A retrospective review of one institution's vascular registry was performed. Logistic regression analysis was conducted to determine independent predictors of 1-, 2- and 3-year postoperative mortality. Creatinine clearance was estimated as [140 - age (years)] x weight (kg)/72 x serum creatinine (mg/dl), multiplied by 0.85 for women. RESULTS: A total of 252 consecutive patients underwent infrainguinal bypass procedures between August 1999 and May 2000. Demographics included average age 68 years, 65% male, 74% diabetic, 12% dialysis-dependent, 23% history of congestive heart failure, 12% history of stroke and 20% serum creatinine >2 mg/dl. One-year mortality was 16% (n = 40), 2-year mortality was 25% (n = 64), and 3-year mortality was 35% (n = 88). There was no difference in serum creatinine values between survivors and non-survivors at 1 year (1.8 vs. 1.9, p = 0.80), 2 years (1.8 vs. 2.0, p = 0.62) or 3 years (1.8 vs. 2.0, p = 0.24), and creatinine >2 mg/dl did not predict long-term adverse outcomes. In contrast, reduced creatinine clearance (< or =60 ml/min) was an independent predictor of mortality regardless of dialysis status (1 year: OR = 2.53, p = 0.014; 2 years: OR = 2.46, p = 0.004; 3 years: OR = 2.45, p = 0.001), and creatinine clearance was higher for survivors versus non-survivors at all 3 time points (1 year: 70.2 vs. 49.5, p = 0.003; 2 years: 72.3 vs. 51.2, p < 0.0001; 3 years: 74.7 vs. 52.6, p < 0.0001). Other independent predictors of mortality included a history of stroke (1 year: OR = 3.28, p = 0.008; 2 years: OR = 2.55, p = 0.025; 3 years: OR = 2.35, p = 0.038) and congestive heart failure (1 year: OR = 2.86, p = 0.006; 2 years: OR = 2.54, p = 0.005; 3 years: OR = 2.13, p = 0.017). CONCLUSIONS: Independent of dialysis status, a decreased creatinine clearance, but not elevated serum creatinine alone, is an independent predictor of mortality after lower extremity arterial reconstruction. Determination of creatinine clearance should replace serum creatinine in the preoperative risk evaluations of patients undergoing major vascular surgical procedures.

Adult↗

Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery.

BACKGROUND: Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment. METHODS: In a group of 8138 patients out of a total of 11878 patients, who underwent cardiac surgery in our hospital between January 1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be determined and logistic regression analysis performed. In all patients scored, creatinine clearance was calculated according to Cockcroft and Gault. The relationship between the predicted and observed 30-days mortality was evaluated in systematically selected intervals of creatinine clearance and significance values computed by employing Monte Carlo methods. Afterwards, risk scoring was performed using a continuous or a categorical value of creatinine clearance instead of serum creatinine. The predictive ability of several risk score models and the individual contribution of their predictor variables were studied using ROC curve analysis. RESULTS: The comparison between the expected and observed 30-days mortalities, which were determined in different intervals of creatinine clearance, revealed the best threshold value of 55 ml/min. A significantly higher 30-days mortality was observed below this threshold and vice versa (both with p < 0.001). The local adaptation of the EuroSCORE is better than the standard EuroSCORE and was further improved by replacing serum creatinine (SC) by creatinine clearance (CC). Differential ROC analysis revealed that CC is superior to SC in providing predictive power within the logistic regression. Variable rank comparison identified CC as the best single variable predictor, even better than the variable age, former number 1, and SC, previously number 9 in the standard set of EuroSCORE variables. CONCLUSION: The renal function is an important determinant of mortality in heart surgery. This risk factor is not well captured in the standard EuroSCORE risk evaluation system. Our study shows that creatinine clearance, calculated according to the Cockcroft and Gault equation, should be applied to estimate the preoperative renal function instead of serum creatinine. This predictor variable replacement gains a significant improvement in the predictive accuracy of the scoring model.

Adult↗

Synthesis of creatinine-imprinted poly(beta-cyclodextrin) for the specific binding of creatinine.

An artificial receptor for creatinine was synthesized by the method of molecularly imprinted polymer (MIP). beta-Cyclodextrin was used as a monomer cross-linked with epichlorohydrin in the presence of creatinine, which was a template for the imprinting. Different molar ratios of monomer to template were used to synthesize the polymers so that better specific adsorption ability towards creatinine could be achieved. The results showed that to carry out the polymerization with a molar ratio of monomer to template of 3:2 and monomer to cross-linking agent of 1:10 was proper. N-hydroxysuccinimide and 2-pyrrolinidone were used as the analogues of creatinine in the adsorption experiments of multi-component solutions to reveal the specific recognition ability of the molecularly imprinted poly(beta-cyclodextrin) (poly(beta-CD)) for the template molecule, creatinine. One such detection interference of creatinine was creatine, which also co-exists in serum. Hence, adsorption experiments of creatinine/creatine binary mixture were also carried out to investigate and confirm the specific binding of the creatinine-imprinted poly(beta-cyclodextrin) towards creatinine. The hydroxyl groups of the imprinted poly(beta-CD) was further capped by chlorotrimethylsilane (CTMS) to investigate the interaction between creatinine and the imprinted poly(beta-CD). The adsorption resulting from the mixture solution by MIPs suggested that the creatinine-imprinted poly(beta-CD) demonstrated superior binding effect for the target molecule, creatinine, rather than creatine, N-hydroxysuccinimide and 2-pyrrolinidone.

Binding Sites↗

Plasma urea, creatinine, and urea: creatinine ratio in reindeer (Rangifer tarandus tarandus) and in Svalbard reindeer (Rangifer tarandus platyrhynchus) during defined feeding conditions and in the field.

Variation in plasma urea and creatinine concentration and plasma urea:creatinine ratio (U:C) were studied in semidomestic free-ranging reindeer (Rangifer tarandus tarandus) on the Norwegian mainland, in wild Svalbard reindeer (Rangifer tarandus platyrhynchus), and in captive reindeer maintained either on a lichen-based diet or a protein-rich concentrate to investigate whether these parameters could be used as indicators of the nutritional status of reindeer. In the mainland animals, plasma creatinine concentration was high in winter and early spring and decreased by two-thirds toward the summer. The overall range in mean plasma creatinine concentration (+/-SE) was from 90+/-1.26 to 280+/-2.88 micromol/L. Mean plasma urea concentration (+/-SE) varied from 2.46+/-0.10 in winter up to 17.44+/-0.29 mmol/L in summer and autumn. Month of sampling explained 65% and 90% of the variation in plasma urea and creatinine concentrations, respectively, indicating that seasonality in the diet had the greatest influence on these parameters. Reindeer given lichens as the only feed showed an increase in plasma creatinine and a decrease in plasma urea concentration. Food restriction caused a temporary elevation in urea level but had no significant effect on plasma creatinine concentration. The slight effect of energy intake on urea and creatinine levels was supported by the fact that severe undernutrition in the Svalbard reindeer population had only a small effect on plasma urea and creatinine levels. Protein-rich pellet feed increased plasma urea from around 3 mmol/L to above 10 mmol/L and reduced creatinine concentrations to less than 100 micromol/L, suggesting that the protein content of forage is an important determinant of these blood parameters. Mean U:C ratio (+/-SE) in plasma varied from 8.9+/-0.28 to 120.8+/-1.88. Ratios above 20 appeared when protein intake was low and energy intake was restricted or when protein intake was high. Low ratios occurred when protein intake was low but energy intake adequate. Plasma urea and creatinine concentrations and the U:C ratio showed complex dynamics that were affected by both season and the protein and feed intake. We conclude that they appear to be difficult to interpret as single measures of nutritional status of reindeer.

Animals↗

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↗

Interference of creatinine measurement in CAPD fluid is dependent on glucose and creatinine concentrations.

BACKGROUND: High glucose concentration in CAPD fluid is known to interfere with creatinine measurement, which is required for assessment of peritoneal membrane permeability and adequacy of dialysis. Correction formulae have been proposed but they may be method/analyser-dependent. We studied such interference in detail. METHODS: CAPD fluid was diluted to prepare six specimens with glucose concentrations ranging from 9.1 to 154.4 mmol/l. To each specimen, creatinine standard was added to give five different concentrations from 50 to 800 mumol/l. The 30 specimens were assayed for creatinine with six routine clinical chemistry analysers (Hitachi 911 and 747, Technicon RAXT and SMAC3, Beckman CX7, and Kodak Ektachem 700). Creatinine interference was calculated by subtracting the apparent creatinine concentration with corresponding baseline creatinine concentration (measured at glucose = 9.1 mmol/l) in the same series. RESULTS: At constant creatinine concentration, interference increased with increasing glucose concentration to varying extents (up to 200%) amongst the six analysers. At constant glucose concentration, interference decreased with increasing creatinine concentration in analysers using the alkaline picrate reaction but increased in the Kodak analyser using enzymatic assay. CONCLUSION: Interference of creatinine measurement in CAPD fluid is dependent on glucose and creatinine concentrations, and each centre should derive specific correction formulae for its analytical system.

Ascitic Fluid↗

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.

Administration, Oral↗

An analysis of the association between preoperative renal dysfunction and outcome in cardiac surgery: estimated creatinine clearance or plasma creatinine level as measures of renal function.

STUDY OBJECTIVES: Preoperative renal dysfunction is a risk factor for adverse events in cardiac surgery. This study compared creatinine clearance (ClCr), estimated from the Cockroft and Gault formula, and plasma creatinine level as predictors of outcome after cardiac surgery. DESIGN: Prospective, observational. SETTING: University hospital. PATIENTS: A total of 6,364 cardiac surgical patients. METHODS: The measured outcomes were postoperative renal failure requiring dialysis, and mortality and major morbidity. For each outcome, two multivariable risk models were developed, using either estimated ClCr as a measure of renal function, or plasma creatinine level. Risk-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each outcome. Discrimination was compared using receiver operating characteristic (ROC) curves. RESULTS: For each 10 mL/min/1.73 m(2) decrement of estimated ClCr, the ORs for renal failure requiring dialysis, mortality, and major morbidity in the whole population were 1.52 (95% CI, 1.35 to 1.67), 1.27 (95% CI, 1.19 to 1.35), and 1.18 (95% CI, 1.14 to 1.21), respectively; for each 0.2 mg/dL increment of plasma creatinine, ORs were 1.20 (95% CI, 1.15 to 1.26), 1.08 (95% CI, 1.04 to 1.13), and 1.12 (95% CI, 1.09 to 1.15), respectively. The areas under the ROC curves for prediction of renal failure requiring dialysis were 0.83 with both risk models. For prediction of mortality and major morbidity, areas under the ROC curves were 0.83 and 0.72, respectively, with the models using estimated ClCr, and 0.74 and 0.65, respectively, with the models using plasma creatinine level (p < 0.001 vs estimated ClCr for both outcomes). In patients with normal plasma creatinine levels (n = 4,603), estimated ClCr remained a significant predictor of each outcome with similar ORs, but plasma creatinine level was not a predictor of any outcome. CONCLUSION: The risk-adjusted association between preoperative renal dysfunction and adverse events after cardiac surgery is stronger with estimated ClCr than with plasma creatinine level, particularly in patients with normal plasma creatinine levels. The routine preoperative estimation of ClCr may improve the identification of higher-risk cardiac surgical patients.

Aged↗

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↗

Creatinine degradation I: the kinetics of creatinine removal in patients with chronic kidney disease.

The existence of an alternative route of excretion for creatinine in subjects with chronic renal failure has been demonstrated. The data presented in this study confirm the hypothesis that creatinine is converted into other metabolites, probably by action of the gut flora. Creatinine degradation was quantitated in a group of subjects that spanned a wide range of kidney functions from normal to no renal function. Five patients were analyzed who were on maintenance dialysis, five were predialysis and two subjects were normal with respect to kidney function. Creatinine degradation expressed as a percentage of production varied from 13.9 to 27.7% in the dialysis patients, 0 to 42.3% in the pre-dialysis patients and was 0% in the controls. Creatinine degradation was correlated with plasma creatinine degradation was correlated with plasma creatinine levels in predialysis (r = 0.73, p less than 0.01), but not in dialysis patients. No correlation was found between creatinine degradation and production in either group. It is concluded that significant amounts of creatinine are degraded in dialysis patients, and this removal mechanism must be accounted for in models of the patient-artificial kidney system.

Adult↗