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Predicted gentamicin elimination rate constants (kelS) using creatinine clearance (Clcr) estimates from seven equations were compared with kelS calculated from steady-state serum gentamicin concentrations in 186 hospitalized patients. In predicting kel, the equations varied significantly in precision (mean absolute percentage error), and were particularly imprecise among patients with serum creatinine values of 71 mumol/L or less. Significant differences in bias (mean prediction error) were also observed. All equations using serum creatinine as an element showed improved precision, and most showed reduced bias when a minimum value of 71 mumol/L was used. The Cockcroft-Gault normalized to 72 kg and the Hull equations are among the simplest to calculate and, when using a minimum serum creatinine of 71 mumol/L, had significantly greater precision and less bias than several of the equations. We recommend one of these two methods for predicting gentamicin kel in patients with low serum creatinine values.
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.
The predictive accuracy of the Cockroft and Gault equation in the assessment of creatinine clearance was evaluated in 30 Nigerian patients with hypertension, congestive heart failure, chronic renal failure and varying degrees of renal impairment. There was a high correlation between the measured and predicted creatinine clearance as shown by the regression equation: measured creatinine clearance = 0.84 predicted creatinine clearance +4.5 ml.min-1 (r2 = 0.74). The prediction error, reflecting the disparity between measured and calculated clearance was low at 2.0 (15.4) ml.min-1. Neither sex nor disease state or level of creatinine concentration had an important effect on the predictive value of the equation in Nigerians.
OBJECTIVES: To examine the relation of estimated creatinine clearance (eCrCl) and plasma total homocysteine (tHcy) in hypertensive patients with a normal serum creatinine level. DESIGN AND METHODS: A total of 137 hypertensive patients (mean age 66.6 years, 69 men) with serum creatinine level </=1.5 mg/dL gave 10-h fasting blood samples for measurement of tHcy, serum folic acid, and serum vitamin B(12). RESULTS: 95 patients fell into a chronic renal insufficiency (CRI) group (eCrCl< or =60 mL/min/1.73 m(2)) and 42 into a normal renal function (NRF) group (eCrCl>60 mL/min/1.73 m(2)). The CRI group was older (p<0.001), had higher tHcy (p<0.001), higher serum urea nitrogen (p<0.001), higher serum creatinine (p<0.001), lower eCrCl (p<0.001), and lower diastolic blood pressure (p=0.001). In univariate analysis, eCrCl had the strongest correlation with tHcy (r=-0.453, p<0.001). Significant correlations, ranging in decreasing order from r=-0.418, p<0.001 to r=-0.170, p=0.047, were also noted between tHcy and twelve other variables. In multivariate analysis, only eCrCl (p<0.001), usage of fibrate (p<0.001), serum level of vitamin B(12) (p=0.002), serum level of folic acid (p=0.009), and smoking (p=0.027) were independent predictors of tHcy. CONCLUSION: eCrCl is a strong independent predictor of tHcy in hypertensive patients with normal serum creatinine.
Creatine, which is increasingly being used as an oral supplement, is naturally present in the body. Studies on the fate of a particular dose of creatine require that the creatine be labeled, and for studies in humans the use of a stable isotopic label is desirable. The concentrations of total creatine and total creatinine were determined using HPLC. Creatine and creatinine were then separated using cation exchange chromatography and each fraction was derivatized with trifluoroacetic anhydride and the ratio of the deuterated:undeuterated species determined using GC-MS. Ratios of creatine:creatine-d(3), and creatinine:creatinine-d(3), and the concentrations of each of these species, were able to be determined in urine, plasma and red blood cells. Thus, the uptake of labeled creatine into plasma and red blood cells and its excretion in urine could be followed for a subject who ingested creatine-d(3). Creatine-d(3) was found in the plasma and red blood cells 10 min after ingestion, while creatine-d(3) and creatinine-d(3) were found in the urine collected after the first hour.
Seven methods using patient's age, weight, gender, and serum creatinine concentration were evaluated for mathematical and clinical predictive performance in estimating the creatinine clearance of Japanese patients. We compared the measured and estimated creatinine clearance in 179 hospitalized heart failure patients. The Gates equation was the most biased (mean prediction error, 17.9 mL/min), and the Yukawa equation was the most precise (mean absolute prediction error, 10.4 mL/min), followed by the Jelliffe, Bjornsson, Cockcroft and Gault, and Mawer equations. For all methods, precision was less when serum creatinine concentrations of <0.6 mg/dL were rounded than when serum creatinine concentrations of >/=0.6 mg/dL were rounded. We conclude that in clinical practice where the renal function can vary widely, any of the published formulas can give satisfactory results. The Yukawa formula is concise and gives better results in Japanese patients.
BACKGROUND: Dosing of allopurinol should be corrected depending on renal function, but corrections based on either plasma creatinine (Pcr) or creatinine clearance (CrCl) have been suggested to be minimal standards of care. METHODS: Data from a cohort database of 484 gouty patients were used to calculate estimated allopurinol doses using CrCl and estimation of the clearance of creatinine using the equation of Cockroft and Gault (CrCl-CG) if, as a hypothesis, a dosage of 300 mg/d would be prescribed in any patient with Pcr <2.0 mg/dL. Also, allopurinol-related toxicity previous to rheumatologic consultation, during previous allopurinol therapy, and the relationship between both and estimated allopurinol doses were reviewed. RESULTS: The cutoff point of plasma creatinine <2 showed 13% sensitivity and 100% specificity to detect CrCl <50 mL/min. Correlation and agreement between CrCl and CrCl-CG were good, as was the correlation between corrected doses using CrCl and CrCl-CG. One third of patients with Pcr 1.0-1.5 mg/dL and 90% of those with Pcr 1.5-2.0 mg/dL would receive estimated doses over 400 mg/dL/d CrCl. Also, 10% and 34% would receive estimated doses over 600 mg/dL/d CrCl, respectively. Allopurinol-related toxicity previous to consultation (11%) was associated with estimated doses over 400 mg/dL/d CrCl and severe toxicity with estimated doses over 600 mg/dL/d CrCl. When patients were given doses corrected on CrCl, few side effects were observed during follow up (6.7%), and the only severe one was associated with corrected dose over 600 mg/d. CONCLUSIONS: Dosage adjustment of allopurinol should be based on clearance of creatinine or estimation of glomerular filtration using the Cockcroft-Gault equation. Pcr is insensitive enough to detect renal function impairment so that patients may be placed at risk for overdosing side effects. Corrected doses over 600 mg/dL/d CrCl may be associated with increased risk of severe toxicity.
Thirteen newborn infants, 8 preterm and 5 term, with either mild or serious neonatal asphyxia were studied. From the first 24 hours of life to day 13, glomerular filtration rate (GFR) estimated by creatinine clearance was compared with the values obtained using Schwartz's formula: GFR (ml/min per 1.73 m2) = 0.55 x length (cm)/plasma creatinine (mg/100 ml). Both in term and preterm infants, values of formula-calculated creatinine clearance were slightly higher than values obtained by the classical method; nevertheless the data show significant correlations, respectively r = 0.867 and r = 0.795 (P less than 0.001). This formula provides an adequate estimation of neonatal creatinine clearance (a marker for GFR) directly from plasma creatinine provided that body length is taken into consideration. The necessity for urine collection and the associated problems are thus obviated. The simplicity of Schwartz's formula permits easy monitoring of renal function, especially in neonatal asphyxia in which the risk of developing renal failure is great.
We examined the plasma urea and creatinine concentrations and the ratio between them according to diagnosis in 100 unselected and 31 selected adult hospital patients with a plasma urea concentration greater than or equal to 10 mmol/l (60mg/100ml). We also examined plasma urea and creatinine concentrations in 350 unselected consecutive patients, but found no useful relation between the two values. Congestive heart failure was the most common identifiable cause of a raised plasma urea concentration in the 100 unselected patients (36%). Among these 100 patinets the plasma creatinine concentration was a more useful discriminant between prerenal uraemia and intrinsic renal failure than was the urea:creatinine ratio or the plasma urea concentration. A plasma creatinine concentration greater than 250 mumol/1 (2-8 mg/100ml) indicated intrinsic renal failure with a 90% probability.
Glomerular filtration rates (GFR) were measured with 51Cr-EDTA in 38 patients (aged 40-75 years) with homozygous sickle cell disease and compared with serum beta 2 microglobulin concentrations in 38 patients and with creatinine clearance in 21 patients. GFR estimated with 51Cr-EDTA was closely correlated with single serum creatinine measurements and the inverse of serum beta 2 microglobulin. Creatinine clearance was also found to be correlated, but values were, on average, 32% below those obtained by the 51Cr-EDTA method, and this difference was significant. It is concluded that measurements of beta 2 microglobulin, single serum creatinine, and creatinine clearance are valuable indicators of GFR in homozygous sickle cell disease. Measurement of beta 2 microglobulin was a useful and reliable method of estimating GFR from single plasma measurements and is therefore a useful means of screening the population.
The aim of this study was to evaluate the possibility of predicting creatinine clearance (CCr) from plasma creatinine (PCr) and body com-position analysis by means of electrical impedance, thereby avoiding urine collection. Fat-free mass (FFM) and body cell mass (BCM) were measured in 50 renal patients (M29, F21; aged 17-74 years; mean 52.6) with different degrees of renal function (PCr 0.8-9.0 mg/dL, mean 2.13) by using a tetrapolar impedance plethysmograph. The relationship between 24 h-urinary creatinine excretion (UCr) and FFM and BCM was evaluated in 20 of the above reported patients (MI I, F9; PCr 0.8-9.0 mg/dL, mean 2.27). The mean ratio of 24 h UCr/FFM was 25.6 mg/kg in males and 22.5 in females and that of 24 h UCr/BCM was 51.9 mg/kg in males and 48.1 in females. CCr was estimated in the remaining 30 patients (M18, F12; PCr 0.9-8.8 mg/dL, mean 2.04) from individual FFM and BCM values and PCr. In the same patients CCr was predicted also according to the Cockcroft and Gault formula and, for comparison, was measured with the conventional method by collecting 24 h urine, CCr predicted from the values of FFM and BCM gave a good estimate of 24 h CCr, more precise than that of Cockcroft and Gault CCR. Also, the repeatability of the predicted CCr was clearly better than that of 24 h CCr. In conclusion, creatinine clearance can be predicted, avoiding urine collection, from plasma creatinine and body composition analysis by means of electrical impedance.
Serum urea and creatinine concentrations were determined in 150 healthy subjects. The formula of Cockcroft and Gault was used in order to calculate creatinine clearance. Such estimation of creatinine clearance is widely used as a parameter for individualization of dosage of drugs secreted primary via the kidneys. The effects of age and sex were then assessed on serum urea, serum creatinine and on creatinine clearance.
Concentrations of endogenous "true" creatinine in saliva and serum were measured in 6 normal subjects using a specific and sensitive high-performance liquid chromatographic method. There were marked intra- and intersubject variations in saliva levels during an 11-wk study. There were also large variations in the ratios of the saliva/serum creatinine level during the one-day study for all the subjects, the average highest intrasubject variation being 481% and the range being 128% to 816%. The average ratio of saliva/serum level was 0.0999 +/- 0.097 (CV = 97%); the highest saliva level was 1.5 mg%. Lower salivary levels were probably due to the extremely low lipid solubility of creatinine resulting in a relatively slower diffusion rate than of the transport of water into the saliva. Salivary monitoring of creatinine is concluded to be of little use in indicating its concentration in plasma or serum because, unlike many other substances it does not follow the pH-partition principle for saliva/plasma distribution.
Immobilized enzyme nylon-tube reactors incorporating creatinine iminohyrolase (CI) and glutamate dehydrogenase (GDH) were used to assay creatinine in serum and urine. Optimum substrate concentrations for the assay were determined. The reactors were incorporated into a continuous flow system for creatinine analysis. The method was evaluated with respect to linearity, sample interaction, precision, accuracy, and analytical recovery. Comparison studies were carried out with a standard Jaffé method and the effect of interfering substances was investigated. From the results obtained, it was concluded that the assay was suitable as a simple, reliable, and specific method for serum and urine creatinine determinations.
In a population of 141 very elderly subjects, there was a small but significant decline in BUN and creatinine at 3 years, which persisted at 6 years although partially attenuated. A similar pattern of falling BUN and creatinine was seen in the 31 subjects who began the study with mild azotemia. There was no significant change in the subjects' mean Body Mass Index during the 6-year period of observation. The azotemic subjects had a rate of death or dropout from the study similar to that of the entire cohort. Mean systolic blood pressure fell by 5.4 mm Hg (p < 0.05) and diastolic blood pressure by 2.1 mm Hg (p = NS) by 6 years. Users of diuretics or NSAID had a mean BUN and creatinine comparable to those not taking these medications. We conclude that BUN and serum creatinine do not necessarily increase with time in the old old, even in those with mild azotemia, hence, several determinations of these parameters may be needed to ensure accuracy. While renal function in the elderly probably does not improve with time, it may stabilize due to improvement in blood pressure. Use of diuretics and NSAID by functioning elderly individuals is not necessarily associated with worsening azotemia.
A case is presented with emphasis on creatinine clearance and burn wound closure. It suggests that the burn wound acts as an extrarenal site for creatinine loss. As a result, renal creatinine clearance may be falsely elevated while the burn wound is open, and closure of the burn wound may affect creatinine clearance.
To devise objective criteria for early diagnosis of delayed graft function (DGF), 59 adult living donor kidney transplants with immediate graft function (IGF) and 51 cadaveric kidney transplants were investigated for creatinine reduction ratio (CRR2) from posttransplant day 1 to day 2 and 24-h urine creatinine excretion (UC2) on day 2. The mean CRR2 in living donor transplants was 53% (SD +/- 11); the distribution of CRR2 was gaussian, and all of them had UC2 >1000 mg. Criteria for DGF were developed on the basis of living donor transplant: CRR2 < or =30% (2SD below 53%) +/- UC2 < or =1000 mg. Overall, 24 cadaver transplant recipients (47%) developed DGF (CRR2 < or =30%); 13 patients (25%) had mild DGF (UC2 >1000 mg), and the remaining 11 (22%) had severe DGF (UC2 < or =1000 mg). All the patients with severe DGF had a measured creatinine clearance <25 ml/min on day 7, and 8 of 11 were dialyzed within the first week of transplantation. Patients with IGF and mild DGF had a creatinine clearance of > or =25 ml/min on or before day 7, and none of them were dialyzed. Calcineurin inhibitors were avoided or delayed in five patients with mild DGF and all patients with severe DGF. In conclusion, diagnosing DGF within 48-h after transplantation is simple and may be valuable in the management of these patients.