Comparison of creatinine and inulin clearances in multiple trauma

Creatinine clearance (Ccr) is a good predictor of renal dysfunction. However, numerous analytical interferences have been observed with the classical measurement of creatinine by Jaffé's procedure. This prospective study was conducted to compare 4 methods for determining creatinine; and also endogenous creatinine clearance with inulin clearance (Cin) to estimate the glomerular filtration rate. The 4 different techniques for measuring creatinine were: 1) 2 techniques using Jaffé's colorimetric reaction: one with rapid and the other with slow kinetics: 2) 2 more selective methods: enzymatic procedure and high performance liquid chromatography (HPLC). Measurements were performed in 13 multiple trauma patients after stabilization and in 5 comatose patients (control group) over a 3-day period, with strict 24-h urine collection. On the second day, inulin clearance and para-aminohippuric acid clearance (Cpah) were measured. Measurement of creatinine by Jaffé's procedure yields significantly higher levels than those obtained by the other methods. Higher levels of both plasma and urinary creatinine were observed in the multiple trauma patients with all the methods used. There were no significant differences in Ccr, Cin, Cpah between the multiple trauma patients and the control patients. The best correlations between inulin clearance and creatinine clearance were observed for Jaffé's rapid kinetics (r = 0.90) in the control group and for the enzymatic procedure in the multiple trauma group (r = 0.55). Plasma creatinine is not a useful indicator in multiple trauma. The correlation between creatinine clearance and inulin clearance is not very strong in multiple trauma, indicating that the relative evolution (not the absolute values) of creatinine clearance is of interest.     

Discrepancy between circadian rhythms of inulin and creatinine clearance.

To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm for inulin clearance with a maximum during daytime and a relative amplitude of 21% +/- 2%. For creatinine clearance a rhythm was either absent or reduced in relative amplitude (p less than 0.01). In all subjects the rate of tubular creatinine secretion was higher at minimum of inulin clearance (night) than at maximum (day). The fractional clearance (relative to inulin) of creatinine was also higher during the night: normal subjects, 1.28 +/- 0.02 versus 1.10 +/- 0.02; patients, 1.78 +/- 0.08 versus 1.45 +/- 0.05 (p less than 0.005). This demonstrates the inaccuracy of creatinine clearance as a measure of glomerular filtration rate (GFR). By subsequent blocking of the tubular secretion of creatinine with cimetidine in four normal subjects, creatinine clearance became similar to inulin clearance during day and night. This confirms that high tubular secretion of creatinine during the night counteracts the normal rhythmicity of glomerular filtration of creatinine. As a result, plasma creatinine concentration is nearly constant during a 24-hour period. In conclusion, tubular creatinine secretion has a circadian rhythm with a phase opposite to the rhythm of GFR, thus blunting or causing absence of a circadian rhythm for creatinine clearance.     

Inulin single injection clearance. Microsample technique useful in children for determination of glomerular filtration rate

Summary. The agreement between single injection inulin (polyfructosan) clearance and two reference methods for glomerular filtration rate (GFR) determination, namely standard inulin constant infusion clearance and 51-Cr-EDTA single injection clearance, was investigated. Studies were also made to see whether different results were obtained when capillary and venous blood samples were used in the single injection clearance method. The investigation was made in children from one year of age, adult patients and volunteers. For the single injection technique with inulin or 51-Cr-EDTA, five to seven blood samples were taken in a period of up to 180 min after injection. A bi-exponential plasma disappearance curve was used for calculations of single injection clearances. Good agreement was obtained between venous inulin single injection clearance on the one hand, and standard inulin clearance (correlation coefficient r= 0·86) and 51-Cr-EDTA single injection clearance on the other (r = 0·85). With use of capillary blood samples in inulin single injection clearance, similar good agreement was obtained both with venous 51-Cr-EDTA and with venous inulin single injection clearance (r = 0·85 and r= 0·89 respectively). From these results we conclude that inulin single injection clearance is a reliable method for GFR determinations. This method is recommended, especially in children, as capillary blood samples can be used.     

Assessing Glomerular Filtration in Small Animals Using [<Superscript>68</Superscript>Ga]DTPA and [<Superscript>68</Superscript>Ga]EDTA with PET Imaging

Purpose

Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals.

Procedures

Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals.

Results

Both tracers did not bind to blood cells. [⁶⁸Ga]DPTA but not [⁶⁸Ga]EDTA showed strong binding to plasma proteins. For this reason, [⁶⁸Ga]DPTA stayed much longer in the blood and only 30 % of the injected dose was eliminated by the kidney within 60 min whereas the excretion of [⁶⁸Ga]EDTA was 89 ± 1 %. The calculated GFR using [⁶⁸Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [⁶⁸Ga]-DPTA, the measurements led to values which were 80 % below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR.

Conclusions

[⁶⁸Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [⁶⁸Ga]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.

     

Assessing glomerular filtration rate in renal transplant recipients by estimates derived from serum measurements of creatinine and cystatin C

BACKGROUND: Assessing glomerular filtration rate (GFR) is of importance in the surveillance of renal transplant recipients. As serum markers alone are inaccurate for estimating GFR, several equations have been developed with the aim of translating a serum value into a corresponding and more accurate GFR. The present study investigated the diagnostic characteristics of GFR estimates obtained by the simplified MDRD formula and the cystatin C based estimate described by Larsson et al. METHODS: Prospective study in 29 stable renal transplant recipients. GFR was assessed with (125)I-Iothalamate clearance, creatinine was measured with a modified Jaffe method on Dimension RxL (Dade-Behring, Dudingen, Switzerland), cystatin C was determined by particle enhanced turbidimetric immunassay (PETIA; Dako, Glostrup, Denmark). Bias, precision and diagnostic accuracy of the two GFR estimates were assessed with Bland-Altman method and receiver-operating characteristics (ROC) analysis. The latter was performed at a GFR cut-off of 60 ml/min/1.73 m2. RESULTS: The cystatin C based GFR estimate normalized to a body surface area of 1.73 m2 exhibited a bias of -4.7 ml/min/1.73 m2, the 95% limits of agreement were -25.5-16 ml/min/1.73 m2 with an AUC of 0.87. The MDRD estimates obtained from the original creatinine revealed biased results. Thus, non-constant recalibration of creatinine was done. Recalibrated creatinine gave an MDRD GFR estimate with a bias of 1.7 ml/min/1.73 m2. The limits of agreement were -23.1-26.4 ml/min/1.73 m2. ROC analysis revealed an AUC 0.8 and was not significantly different from the cystatin C based GFR estimate. CONCLUSIONS: In renal transplant recipients, the cystatin C based GFR estimate exhibits similar diagnostic characteristics like the simplified MDRD formula. In contrast to cystatin C measurement, recalibration of creatinine might be necessary before implementing the simplified MDRD formula into clinical routine.     

Plasma clearance of iodine contrast media as a measure of glomerular filtration rate in critically ill patients

OBJECTIVE: The selection of the optimal method for assessing renal function relies on the accuracy of the technique. Plasma clearance of nonradioactive iodine contrast media (i.e., iohexol or iopromide) has been suggested as a reliable alternative to the renal clearance of inulin for estimating glomerular filtration rate (GFR). The accuracy of this method when used with critically ill patients displaying different levels of renal function in an intensive care unit (ICU) has not, until now, been examined. DESIGN: The accuracy of double- and multiple-point iohexol or iopromide plasma clearances was compared with that of already established techniques for measuring GFR (creatinine clearance, formula clearance by Cockcroft and Gault) and with that of inulin clearance, which is regarded as the gold standard for the measurement of GFR. PATIENTS: Values were obtained from 31 ICU patients who exhibited a wide range of renal function (serum creatinine: 0.6-6.7 mg/dL). MEASUREMENTS: Inulin clearance was performed using the constant-infusion technique. Creatinine clearance was determined from 24-hr urine samples. The clearance formula was calculated according to Cockcroft and Gault's formula. Iohexol or iopromide were applied as a single intravenous dose, and blood samples were taken up to 6 hrs after the injection. Iodine concentrations were determined by radiographic fluorescence. RESULTS: Plasma clearance of iohexol/iopromide measured after the single injection of contrast media and that of the conventional inulin clearance was almost identical (y = 0.971x + 7.65, r2 =.96; n = 31). Two-point clearance of iohexol/iopromide (double sampling technique) was as reliable as the three-point clearance (three-slope-intercept method, y = 0.995x + 0.62, r2 =.999; n = 18). With respect to inulin clearance, GFR measurements determined by creatinine clearance or according to the formula given by Cockcroft and Gault revealed errors that increased proportionally (y = 1.03x, r2 =.88; n = 27; and y = 0.93x, r2 =.62; n = 31, respectively). It could also be shown that the accuracy of GFR measurements involving plasma clearance of iohexol was not greatly affected by the degree of renal insufficiency or the route by which contrast media were applied. CONCLUSION: These findings indicate that the determination of plasma clearance of iohexol/iopromide is a simple, rapid, and accurate method that can indeed be used for estimating GFR in ICU patients with normal renal function or even different degrees of renal insufficiency.     

Practical approach for determining glomerular filtration rate by single-injection inulin clearance.

We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.     

Measurement of glomerular filtration rate in children with insulin-dependent diabetes mellitus

51Cr-EDTA, inulin and creatinine clearances were measured simultaneously in 11 diabetic children and 12 healthy young adults. The clearances in all individuals were 115 +/- 24 ml/min per 1.73 m2SA for 51Cr-EDTA, 118 +/- 25 ml/min per 1.73 m2SA for inulin and 157 +/- 35 ml/min per 1.73 m2SA for creatinine. Values were higher in the diabetic children but the differences were not significant. 51Cr-EDTA clearance significantly underestimated that of inulin by a mean of -7.4 +/- 2.5 (SEM) ml/min per 1.73 m2SA (p less than 0.01) and creatinine clearance significantly overestimated that of inulin by 37.6 +/- 3.3 (SEM) ml/min per 1.73 m2SA (p less than 0.0001). Similarly, the mean ratio of 51Cr-EDTA to inulin clearance was 0.94 (95% CI 0.90-0.98) and that of creatinine to inulin clearance was 1.32 (95% CI 1.27-1.37); the differences between diabetics and controls were not significant. Correlation coefficients were 0.93 between 51Cr-EDTA and inulin clearances, and 0.95 between inulin and creatinine clearances. The pooled coefficient of variation between clearances within an individual was higher with inulin, 10.3 +/- 6.5% (SD), than 51Cr-EDTA, 7.3 +/- 5.1% (p less than 0.001, t test). These results show that 51Cr-EDTA clearance underestimates that of inulin to a similar extent in both diabetic children and healthy controls and creatinine clearance overestimates inulin clearance to a greater but similar extent in both groups. The methodological variation in 51Cr-EDTA measurement is less than with the other 2 methods. Therefore, we recommend the use of the renal clearance of 51Cr-EDTA for the measurement of GFR in diabetic children.     

Evaluation of the IRMA TRUpoint and i-STAT creatinine assays

BACKGROUND: The i-STAT (Abbott Diagnostics, East Windsor, NJ) and IRMA TRUpoint (ITC, Edison, NJ) POCT analyzers were evaluated in an oncology center. METHODS: Precision and agreement with our core laboratory creatinine was judged by comparison of 50 consecutive chemotherapy patient results against the Roche rate-blanked Jaffe and enzymatic creatinine methods. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault (CG) calculation and Modification of Diet in Renal Disease Study (MDRD) equation. RESULTS: Precision varied from 1% (enzymatic)-6.1% (TRUpoint). Correlation was good (r>0.9948) with slopes within 5% of the Jaffe and enzymatic methods. Intercepts were <15.9 micromol/l (<0.18 mg/dl), and statistically significant bias (p<0.0025) was noted between the mean of patient specimens for i-STAT correlations to both the Jaffe and enzymatic laboratory creatinine methods. There was statistically significant concordance of estimated GFR between all methods, however, the agreement of estimated GFR to either the Jaffe or enzymatic creatinine laboratory methods was better for the TRUpoint (by either MDRD or CG estimation) and i-STAT (by MDRD equation) (Kappa>0.60) than the i-STAT (by CG estimation) (Kappa=0.41-0.60). CONCLUSION: Small biases in the calibration of analytical creatinine methods can lead to differences in clinical concordance using estimated GFR. Selecting an optimal POCT method depends on the institution's current creatinine method and tolerance for analytical performance and clinical concordance.     

Cimetidine administration and tubular creatinine secretion in patients with compensated cirrhosis.

Cimetidine inhibits the tubular secretion of creatinine, without altering the glomerular filtration rate (GFR). During cimetidine administration the creatinine/inulin clearance ratio approaches unity in patients with renal failure. We determined the clearance of lithium (an index of fluid delivery to the distal nephron), inulin (a measure of the actual GFR) and creatinine during cimetidine administration to investigate the occurrence of tubular creatinine secretion in patients with compensated cirrhosis. A total of 12 patients with Child-Pugh A cirrhosis were studied initially. The subjects consumed a stable diet containing 100 mmol of sodium. On successive days, 9 h creatinine clearances were measured, first without and then with the oral administration of cimetidine (400 mg as a priming dose, followed by 200 mg every 3 h). During the first study day, 4 h renal lithium clearance was also calculated. A further group of five patients with fully compensated cirrhosis underwent the measurement (on successive days) of plasma inulin clearance, first without and then with the oral administration of cimetidine (same schedule of drug administration). Cimetidine administration unmasked a marked overestimation of GFR when calculated as creatinine clearance (baseline, 138+/-20 ml/min; +cimetidine, 89+/-13 ml/min; P<0.01). Consequently, during cimetidine administration the calculated lithium fractional excretion (a measure of the fraction of filtered sodium load that is delivered to the loop of Henle) rose from 21.4+/-13.2% to 32.3+/-18.9% (P<0.05), and the ratio between absolute distal tubular sodium reabsorption and filtered sodium load rose from 20.6+/-13.1% to 31.6+/-19.3% (P<0.01). Cimetidine caused no significant decrease in the actual GFR (i.e. inulin clearance) when administered to the second group of patients with compensated cirrhosis. Our data demonstrate significant tubular secretion of creatinine in patients with compensated cirrhosis and, consequently, a marked overestimation of GFR and filtered sodium load and an underestimation of the fractional distal tubular sodium reabsorption when these parameters are calculated by means of the traditional creatinine and lithium clearance computation. The true GFR (measured as inulin clearance) is unaffected by cimetidine administration.     

Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function

BACKGROUND: To determine the potential sensitivity of several renal function tests for detecting early changes in renal function, we compared the within-individual (W-I) variation over 5 months of serum creatinine, serum cystatin C, and creatinine clearance. METHODS: On 31 healthy subjects, blood and timed urine specimens were collected once each month to get 6 collections. Creatinine (enzymatic) in serum and urine and cystatin C (immunonephelometric) in serum were measured and glomerular filtration rate (GFR) by creatinine clearance and the Modification of Diet in Renal Disease (MDRD) equation were calculated. To compare W-I variations between different creatinine methods, we also measured creatinine by both enzymatic and kinetic alkaline picrate methods on 15 sets of frozen samples. RESULTS: For the 31 volunteers, the mean W-I variations for serum creatinine (5.8%) and cystatin C (5.4%) were both much lower than the W-I variation of creatinine clearance (18.7%). As expected, the MDRD GFR had a similar W-I variation (6.7%) to that of serum creatinine and its values were markedly different than GFR by creatinine clearance. On the 15 sets of frozen samples, the W-I variation of creatinine measured by the enzymatic method (CV 5.2%) was slightly less than by the picrate method (CV 6.2%). CONCLUSIONS: The low W-I variation of both serum cystatin C and serum creatinine suggests that serial measurements of either would detect a changes in renal function earlier than would GFR by creatinine clearance or MDRD equation, which allows reporting only for GFRs<60 ml/min/1.7 m(2). While we measured only creatinine clearance, the large variability, difficulty, and cost of all clearance measurements make them impractical for routine monitoring of patients.     

A multicentric evaluation of IDMS-traceable creatinine enzymatic assays

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9±0.9 μmol/L to 174.5±3.1 μmol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4±1.4 μmol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9±0.9 μmol/L), the bias ranged from -1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40 μmol/L.     

苦味酸法和酶法检测肌酐对肾小球滤过率预测公式效能的影响

目的 探讨应用苦味酸法和酶法检测肌酐对GFR评估方程适用性的影响.方法 选取2007-2009年华北(北京)、东北(大连)、华东(上海)、华中(长沙)4个区域三级甲等综合医院CKD患者176例.以双血浆法99m Tc-二乙三胺五乙酸(99mTc-DTPA)血浆清除率作为176例CKD患者的rGFR.使用4个不同厂家的酶法或苦味酸法肌酐试剂配套不同厂家自动生化分析仪分别测定患者血肌酐,同时应用体表面积( BSA)标化的Cockcroft-Gault方程(CG/BSA方程)、简化MDRD方程、校正至同位素稀释质谱法的简化MDRD方程(MDRD-IDMS方程)、CKD流行病学合作研究方程(CKD-EPI方程)及2个国内简化MDRD改良方程(课题组方程1、2)分别计算eGFR,比较不同估算结果与rGFR的相关性、偏差、精密度以及30％准确性.结果 176例CKD患者的rGFR为[40.70(19.41～84.35)] ml·min-1·(1.73 m2)-1.应用苦味酸法测定肌酐时,各方程评估的eGFR与rGFR的ICC在0.879～0.923之间;应用酶法测定肌酐时,各方程评估的eGFR与rGFR的ICC在0.925 ～0.946之间,相关性优于应用苦味酸法测定肌酐.Bland-Altman图显示,各方程评估的eGFR在高值区偏差较大,但用酶法时偏离程度均小于应用苦味酸法.在rGFR≥60 ml·min-1·(1.73 m2)-1时,各方程应用酶法测定肌酐时的30％准确性在68.3％～90.0％之间,应用苦味酸法30％准确性在41％～75％之间,除课题组方程1外,其他方程应用酶法测定肌酐时的准确性均显著高于苦味酸法.而rGFR＜60ml· min-1·(1.73 m2)-1时,应用酶法、苦味酸法测定肌酐的30％准确性分别在39.7％～49.1％、40.5％～52.6％之间.对于同一方程,应用酶法测定肌酐的两套不同检测系统间,其30％准确性差异无统计学意义,而应用苦味酸法的两套不同检测系统间,其30％准确性差异有统计学意义.结论 同一评估方程使用苦味酸法和酶法两种不同的肌酐检测方法时,结果存在显著性差异.采用酶法测定肌酐时,方程评估的eGFR结果在相关性、偏离程度、准确性方面均优于苦味酸法.     

Impact of serum creatinine measurement error on dose adjustment in renal failure

BACKGROUND: Doses of renally eliminated drugs should be adjusted according to kidney function to prevent adverse drug events and cost. Dose adjustment can be based on serum creatinine level, subsequent creatinine clearance estimation, and dosage calculation with consideration of the renal elimination properties of the respective compound. OBJECTIVE: Our objective was to quantify the impact and relevance of serum creatinine measurement error on dose adjustment in renal failure. METHODS: We analyzed 27914 measurements from external quality assessment surveys of 1878 German laboratories that used a kinetic alkaline picrate (69% of results) or an enzymatic method (25%) for creatinine determination. Linear models were fit for both methods combined and separately. On the basis of 95% confidence intervals (CIs) for creatinine values, 95% CIs for drug dosing were calculated. RESULTS: The 95% CI for a measured serum creatinine value was 0.80. Measured value < Reference method value < 1.28. Measured value for the kinetic alkaline picrate method and 0.87. Measured value < Reference method value < 1.21. Measured value for the enzymatic method. Applied to a data set of 6.5 million simulated patients with all possible combinations of characteristics relevant for drug dosing, the dosing error caused by serum creatinine measurement error did not exceed 25% in patients with creatinine clearance estimates lower than 50 mL/min according to the Cockcroft-Gault equation. For drugs completely eliminated by the kidneys in active form, the dosing error was up to 6-fold smaller than that which would occur if doses were not adjusted. CONCLUSION: The serum creatinine measurement error of current laboratory methods is small and is comparable to other errors influencing dose adjustment.     

A simple method for the estimation of glomerular filtration rate

A simple method is presented for indirect estimation of the glomerular filtration rate from two venous blood samples, drawn after a single injection of a small dose of [125I]sodium iothalamate (10 muCi). The method does not require exact dosage, as the first sample, taken a few minutes (t = 5 min) after injection, is used to normalize the value of the second sample, which should be taken in between 2-4 h after injection. The glomerular filtration rate, as measured by standard inulin clearance, may then be predicted from the logarithm of the normalized value and linear regression formulas with a standard error of estimate of the order 1-2 ml/min/1.73 m2. The slope-intercept method for direct estimation of glomerular filtration rate is also evaluated and found to significantly underestimate standard inulin clearance. The normalized 'single-point' method is concluded to be superior to the slope-intercept method and more sophisticated methods using curve fitting technique, with regard to predictive force and clinical applicability.     

Compensating for the influence of total serum protein in the Schwartz formula

Abstract Background: The Schwartz 2009 creatinine-based revised formula is the only pediatric GFR estimating formula, which is compatible with the recent global creatinine standardization. This formula is only applicable if enzymatic creatinine methods are used. We propose an equation, taking into account the relative bias caused by serum proteins to use Jaffe based creatinine data for GFR estimation. Methods: In a cohort study of 100 pediatric patients, serum creatinine was measured using a kinetic rate-blanked Jaffe assay (modified kinetic alkaline picrate method), a kinetic rate-blanked Jaffe compensated assay for reactive proteins and an enzymatic assay (creatinine plus method). Serum total protein, albumin, urea, uric acid and total bilirubin were measured with the use of commercial agents. Results: The difference in serum creatinine between the enzymatic method and the compensated Jaffe method was mainly dependent on the total protein concentration in serum (r2=0.61, p<0.001). After applying the proposed protein correction, corrected compensated Jaffe results and creatinine clearance values became interchangeable with enzymatic serum creatinine results (r2=0.99, p<0.001; Deming regression: slope: 0.9787, intercept: -0.351) and with the newly proposed Schwartz formula, respectively (r2=0.99, p<0.001; Deming regression: slope 1.004, intercept: 2.16). Conclusions: In this study, we demonstrated the usability of the alkaline picrate method in the Schwartz formula, taking into account the relative bias caused by serum proteins.     

The effects of mannitol diuresis on digoxin and phenobarbital handling by the kidney: implications for tubular reabsorption and secretion of the cardiac glycoside

The effect of mannitol diuresis on the renal clearance of digoxin and phenobarbital was studied in dogs. Mannitol diuresis significantly increased the clearance of digoxin and the ratio digoxin: inulin clearances (from 0.7 +/- 0.2 to 1.1 +/- 0.25). The increase in phenobarbital: inulin clearance ratio was significantly higher than the increase in the digoxin: inulin clearance ratio (4.9 fold vs 1.66 fold) (p less than 0.005). Mannitol diuresis did not significantly affect inulin clearance, nor digoxin protein binding during the experimental period while there was a significant increase in PAH clearance. Significant correlations were found between urine flow rate and digoxin renal clearance or digoxin: inulin clearance ratio. The increase in the ratio drug: inulin clearance with diuresis correlated inversely with the initial ratio; animals with more predominant net reabsorption had a higher increase in ratio. These studies suggest that the mannitol-induced increase in digoxin clearance stems from a combination of increased renal blood flow enhancing digoxin secretion, and increased urine flow rate inhibiting its reabsorption. We conclude that urine flow rate and renal blood flow are important determinants of the renal clearance of digoxin, independent of GFR. Any study assessing the effect of pathophysiological states or drug interactions on digoxin renal clearance must control for these factors.     

Clinical benefits of using inulin clearance and cystatin C for determining glomerular filtration rate in HIV-1-infected individuals treated with dolutegravir

Introduction

Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys).

Transcutaneous Renal Function Monitor: Precision During Unsteady Hemodynamics

Objective. Hospital acquired renal dysfunction, most commonly caused by renal hypoperfusion, dramatically increases mortality in intensive care patients. Glomerular filtration rate (GFR) is rapidly altered during renal hypoperfusion, and a more rapid means of GFR measurement may prompt institution of renal-specific therapy. We hypothesized that a transcutaneous renal function monitor can rapidly and accurately assess acute changes in GFR within a time frame much shorter than the 2–4 hours currently available. Methods. The study design was a prospective determination of the capability to measure GFR transcutaneously. In three different studies, concurrent transcutaneous measurement of GFR, using the rate of disappearance of ^99m Tc-diethylenetriaminepentaacetic acid (DTPA), was compared by correlation and standard deviation (SD) to reference standards of DTPA plasma clearance, serum inulin clearance, or serum creatinine. Results. Continuous transcutaneous clearance (TC) measurement correlated with standard DTPA plasma clearance techniques (r = 0.93). Acute pharmacologically induced changes in GFR are detectable by TC measurement within 12–20 min, a time interval significantly affected by the data acquisition interval. Excess patient movement in the ICU patients created clearance artifacts in 50% of clearance traces. Retrospective analysis of ICU patient data reveal TC measurements are 93% specific and 92% sensitive for serum creatinine levels in critically ill patients. Conclusions. TC monitoring provides prompt indication of directional changes in GFR and may provide the clinician warning of inadequate resuscitation. Prospective analysis of the specificity, sensitivity, and TC guided renal-specific resuscitation is needed.     

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.