Measurement Of Creatinine Concentration Research Articles

Interference of metamizole in the measurement of serum creatinine concentration.

There is little literature on the interference of metamizole in measurement creatinine concentration by the enzymatic method. Some studies have postulated that the dipyrone molecule is responsible for interfering in the last reaction of the enzymatic method sequence, due to its similarity with the 4-aminophenazone molecule. The aim of this study is to examine the interference of the presence of metamizole in the measurement of serum creatinine concentration by the enzymatic method. An interference study of the measurement of creatinine concentration was carried out with two measurement procedures (enzymatic and Jaffe), by adding different concentrations of metamizole to pool from 30 serum samples of patients. The interference study indicates that the results of serum creatinine concentrations in patients, as measured by the enzymatic method, decrease with the addition of increasing concentrations of metamizole. There is interference with metamizole in the measurement of serum creatinine concentration by the enzymatic method that it is have not seen in the Jaffe method.

COMPARATIVE EVALUATION OF CREATININE IN SERUM AND SALIVA OF CHRONIC KIDNEY DISEASE PATIENTS

Background & objectives: Chronic kidney disease (CKD) is progressive reduction in renal function. Renal excretory function can be assessed by measurement of creatinine concentrations in plasma which illustrates the ltration capacity of the glomerulus. The increased serum creatinine levels in CKD patients create a concentration gradient that facilitates increased diffusion of creatinine from serum into the saliva. Saliva has many advantages as a diagnostic media over serum, which includes non-invasive collection, good patient compliance, minimal risk of contracting infection, repeated sampling possible and is cost effective. The purpose of this study was to estimate and correlate serum and salivary creatinine in patients with CKD and to evaluate use of salivary creatinine as an alternative biomarker to serum creatinine in CKD patients. A total sample of 40 subjects aged 25 -6 Methods: 5yrs, inclusive of both genders comprising 20 cases of healthy controls (Group I) and 20 diagnosed cases of CKD (Group II) were selected. 2ml of blood and unstimulated whole saliva was collected from both the groups. The blinded samples were processed in autoanalyzer using Jaffe's kinetic reaction. The collected data were subjected to Statistical analysis. In the present Results: study we found signicant correlation of serum creatinine and salivary creatinine in both controls and CKD. Serum creatinine (6.21 ±4.02) and Salivary creatinine (0.70± 0.61) were both increased in CKD cases compared to Controls Serum creatinine (0.83±0.21) and Salivary creatinine (0.11± 0.07). Serum creatinine and salivary creatinine were xii both increased as CKD progressed. A sensitivity of 75% and specicity of 90% of salivary creatinine was found. We therefore recommend Conclusion: salivary creatinine as a biomarker in CKD and also as an alternative biomarker to serum creatinine in detecting and staging CKD, for assessing disease progression, therapeutic modalities and in screening of large population

Improving the activity of creatinase from Alcaligenes sp. KS-85 through semi-rational design

Creatinine levels in biological fluids are important indicators for the clinical evaluation of renal function. Creatinase (CRE, EC3.5.3.3) is one of the key enzymes in the enzymatic measurement of creatinine concentration, and it is also the rate-limiting enzyme in the whole enzymatic cascade system. The poor catalytic activity of CRE severely limits its clinical and industrial applications. To address this issue, a semi-rational design is applied to increase the activity of a creatinase from Alcaligenes sp. KS-85 (Al-CRE). By high-throughput screen of saturation mutagenesis libraries on the selected hotspot mutations, multiple variant enzymes with increased activity are obtained. The five-point best variant enzyme (I304L/F395V/K351V/Y63S/Q88A) were further obtained by recombine the improved mutations sites that to showed a 2.18-fold increased specific activity. Additionally, structure analysis is conducted to understand the mechanism of the activity change. This study paves the way for a better practical application of creatinase and may help further understand its catalytic mechanism.

GFR Estimation in Potential Living Kidney Donors: Race- and Nonrace-based Equations and Measured GFR

Recent studies evaluated and proposed new race-neutral, creatinine-based glomerular filtration rate (GFR) estimation equations. The performance of these equations in diverse potential living kidney donors requires study. Cross-sectional study. 637 potential living kidney donors from one tertiary hospital with serum creatinine concentration measurement and GFR measurement by iohexol plasma clearance between October 2016 and December 2020. Creatinine-based estimation of GFR by Chronic Kidney Disease Epidemiology Collaboration (2009, CKDEPI09; 2021, CKDEPI21) and Modification of Diet in Renal Disease equations with and without inclusion of race coefficient, where applicable. Equation bias, precision, accuracy, and accurate classification of GFR as equal to and above or below 80mL/min/1.73m2. GFR estimation equation performance compared to measured GFR (mGFR) by iohexol clearance. The median bias of the CKDEPI21 equation underestimated mGFR by 2.8mL/min/1.73m2. The bias in the Black subgroup underestimated mGFR by 9.0mL/min/1.73m2. Compared to CKDEPI09 with and without race adjustment, the accuracy of CKDEPI21 increased across all subgroups. On average, 3.9% of individuals were misclassified by CKDEPI21 as having a GFR greater than, and 8.9% misclassified less than, 80mL/min/1.73m2, compared to 3.1% and 13.2% for CKDEPI09 with race adjustment, respectively. Total misclassification (either above or below 80mL/min/1.73m2) was 16.3% for CKDEPI21 and 16.0% for CKDEPI09 (with race adjustment). Limited sample of individuals identifying as Black. Lack of cystatin C data. In our potential living donor sample, GFR estimation by creatinine-based CKDEPI21 is less biased and more accurate than previous creatinine-based estimated GFR equations. When evaluated by race, this summative improvement remains in individuals identifying as Asian, Hispanic, or White. More external validation is needed to assess whether the new equation is an improvement over the previous CKDEPI equation with a race coefficient.

A smartphone-integrated portable rotating platform for estimation of concentration level of plasma-creatinine using whole human blood

The measurement of creatinine concentration is performed to monitor the renal health. The devices available in modern clinical laboratories for measuring creatinine concentration are accurate and provide results rapidly but may be prohibitively expensive for resource-poor settings. Therefore, developing an inexpensive yet accurate device for measuring creatinine concentration is needed. Consequently, we developed a simple, affordable, and portable spinning disc for measuring plasma-creatinine concentration with 10 μL of whole human blood.5 μL of the alkaline picrate solution is loaded into the device and rotated at 1000 rpm to transport this solution to the periphery of the microchannel. Further, 10 μL whole blood is loaded in the same channel and spun at 1300 rpm for 10 min. The creatinine in plasma reacts with alkaline picrate (Jaffe reaction), and the color of the mixture changes to yellow-orange color. The resulting color is captured with a smartphone, and creatinine concentration is estimated using an in-house developed app (CREA-SESE).The value of creatinine measured with the present device and the gold standard device are highly correlated (R2 = 0.998). The bias and standard deviation of the difference between the two measurements are 0.134 mg/dL and 0.143 mg/dL. This study demonstrates the feasibility of a simple, inexpensive, and portable rotating device for measuring creatinine concentration using 10 μL of whole human blood, which can easily be deployed to the underserved population in resource-constrained settings to monitor renal diseases.

An optimal method for measuring biomarkers: colorimetric optical image processing for determination of creatinine concentration using silver nanoparticles.

Creatinine concentration is one of the important elements in the body for diagnosing kidney failure, muscular dystrophy, glomerular filtration rate, and diabetic nephropathy. The disadvantages of recently introduced analytical techniques, such as Jaffe's, spectroscopic, colorimetric, and chromatographic methods, for quantifying creatinine in urine involve toxicity, the high cost, interference, and the complexity of the design. In this paper, we designed and fabricated a new colorimetric assay for the measurement of creatinine concentration based on color differentiation generated by mixing different concentrations of creatinine with synthesized silver nanoparticles (AgNPs) coated with polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). An isolated box is designed for the uniform optical imaging of solutions, the captured images are processed in real time, and the quantitative and qualitative results are displayed. For colorimetric processing, a variety of color systems, such as RGB (red, green, blue), CMYK (cyan, magenta, yellow, black), and grayscale (Gr), have been evaluated, indicating that the combination of green (G) and grayscale (Gr) provides the best results for this experiment. TEM analysis and spectroscopy were used to confirm the results of the experiment. Linear range and limit of detection (LOD) were obtained for AgNPs/PVP 0.03-1mg/dl and 0.024mg/dl and for AgNPs/PVA 0.01-1mg/dl and 0.014mg/dl, respectively, indicating the superiority of our proposed method over recently introduced methods. In this experiment, the detectable resolution with AgNPs/PVP is 40, while it is 71 with AgNPs/PVA. The designed system is simple to use, small in size, and cost-effective for measuring creatinine concentration, while it can be used as a portable system.

Evaluation of a point-of-care serum creatinine measurement device and the impact on diagnosis of acute kidney injury in pediatric cardiac patients: A retrospective, single center study.

Background and aimsAgreement between measurements of creatinine concentrations using point‐of‐care (POC) devices and measurements conducted in a standard central laboratory is unclear for pediatric patients. Our objectives were (a) to assess the agreement for pediatric patients and (b) to compare the incidence of postoperative acute kidney injury (AKI) according to the two methods.MethodsThis retrospective, single‐center study included patients under 18 years of age who underwent cardiac surgery and who were admitted into the pediatric intensive care unit of a tertiary teaching hospital (Okayama University Hospital, Japan) from 2013 to 2017. The primary objective was to assess the correlation and the agreement between measurements of creatinine concentrations by a Radiometer blood gas analyzer (Cregas) and those conducted in a central laboratory (Crelab). The secondary objective was to compare the incidence of postoperative AKI between the two methods based on Kidney Disease Improving Global Outcomes (KDIGO) criteria.ResultsWe analyzed the results of 1404 paired creatinine measurements from 498 patients, whose median age was 14 months old (interquartile range [IQR] 3, 49). The Pearson correlation coefficient of Cregas vs Crelab was 0.968 (95% confidence interval [CI], 0.965‐0.972, P < 0.001). The median bias between Cregas and Crelab was 0.02 (IQR ‐0.02, 0.05) mg/dL. While 199 patients (40.0%) were diagnosed as having postoperative AKI based on Crelab, 357 patients (71.7%) were diagnosed as having postoperative AKI based on Cregas (Kappa = 0.39, 95% CI, 0.33‐0.46). In a subgroup analysis of patients whose Cregas and Crelab were measured within 1 hour, similar percentage of patients were diagnosed as having postoperative AKI based on Cregas and Crelab (42.8% vs 46.0%; Kappa = 0.76, 95% CI, 0.68‐0.84).ConclusionThere was an excellent correlation between Cregas and Crelab in pediatric patients. Although more patients were diagnosed as having postoperative AKI based on Cregas than based on Crelab, paired measurements with a short time gap showed good agreement on AKI diagnosis.

373. Evaluation of the StatSensor Xpress for the point of care determination of capillary creatinine concentration in a pregnant population

Introduction Early identification of Acute Kidney Injury during pregnancy (P-AKI) is critical to reduce adverse maternal and fetal outcomes. The StatSensor Xpress (Nova Biomedical) is a handheld device that may improve feasibility of rapid, serial creatinine concentration measurement, especially in low resource settings with a high incidence of P-AKI. Prior to implementation the device requires validation in a pregnant population. Objective To evaluate the performance of the StatSensor Xpress creatinine analyser in capillary blood compared to an enzymatic serum assay, in a pregnant population. Methods Serum and capillary blood samples were obtained prospectively from pregnant participants at antenatal obstetric clinics, and non-pregnant controls. Repeatability was assessed in quality control lots and venous blood from three participants at low (50 μmol/L), mid (90 μmol/L) and high (200 μmol/L) concentrations. Creatinine concentration was determined using an enzymatic reference method in serum samples and StatSensor in capillary blood, as per manufacturer’s specifications. Agreement was assessed by concordance and construction of Bland–Altman plots. A retrospective adjustment factor was separately applied to evaluate the inbuilt offset function. Results Coefficients of variation (CV) from repeatability analysis, ranged from 2.1 to 3.0%CV in aqueous solution and 4.0%CV, 3.0%CV and 4.1%CV in whole blood samples of low, mid and high creatinine concentrations respectively. Lin’s concordance correlation coefficients between the methods were 0.95 (n = 15), and 0.96 (n = 11) when non-pregnant participants were excluded. The median difference between methods was +12 μmol/L. Discussion The StatSensor met desirable criteria for precision and accuracy. 95% limits of agreement were adequate once systematic bias was corrected for by retrospective application of an adjustment factor, which can be used for future analysis. Device performance may be superior in pregnancy due to the lower serum creatinine concentration observed secondary to glomerular hyperfiltration. Findings require replication in a larger population with prospective evaluation of the offset function.

Biological correlates of self-reported new and continued abstinence in cannabis cessation treatment clinical trials

BackgroundThe agreement between self-reported cannabis abstinence with urine cannabinoid concentrations in a clinical trials setting is not well characterized. We assessed the agreement between various cannabinoid cutoffs and self-reported abstinence across three clinical trials, one including contingency management for abstinence. MethodsThree cannabis cessation clinical trials where participants reported use and provided weekly urine samples for cannabis and creatinine concentration measurements were included. Bootstrapped data were assessed for agreement between self-reported 7+ day abstinence and urine cannabinoid tests using generalized linear mixed effects models for clustered binary outcomes. One study implemented contingency management for cannabis abstinence. Four hundred and seventy-three participants with 3787 valid urine specimens were included. Urine was analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and creatinine using immunoassay methods Biological cutoffs of 50, 100, and 200 ng/ml, as well as changes in CN normalized THCCOOH (25%/50% decrease), were assessed for agreement with self-reported abstinence during the three clinical trials. ResultsAgreement between measured THCCOOH and self-reported abstinence increases with increasing cutoff concentrations, while the agreement with self-reported non-abstinence decreases with increasing cutoff concentrations. Combining THCCOOH cutoffs with recent changes in CN-THCCOOH provides a better agreement in those self-reporting abstinence. Participants in the studies that received CM for abstinence had a lower agreement between self-reported abstinence and returned to use than those in studies that did not have a contingency management component. ConclusionUsing combinations of biological measurements and self-reported abstinence, confirmation of study related abstinence may be verifiable earlier and with greater accuracy than relying on a single measurement.

Multilevel pharmacokinetics-driven modeling of metabolomics data

IntroductionMultilevel modeling is a quantitative statistical method to investigate variability and relationships between variables of interest, taking into account population structure and dependencies. It can be used for prediction, data reduction and causal inference from experiments and observational studies allowing for more efficient elucidation of knowledge.ObjectivesIn this study we introduced the concept of multilevel pharmacokinetics (PK)-driven modelling for large-sample, unbalanced and unadjusted metabolomics data comprising nucleoside and creatinine concentration measurements in urine of healthy and cancer patients.MethodsA Bayesian multilevel model was proposed to describe the nucleoside and creatinine concentration ratio considering age, sex and health status as covariates. The predictive performance of the proposed model was summarized via area under the ROC, sensitivity and specificity using external validation.ResultsCancer was associated with an increase in methylthioadenosine/creatinine excretion rate by a factor of 1.42 (1.09–2.03) which constituted the highest increase among all nucleosides. Age influenced nucleosides/creatinine excretion rates for all nucleosides in the same direction which was likely caused by a decrease in creatinine clearance with age. There was a small evidence of sex-related differences for methylthioadenosine. The individual a posteriori prediction of patient classification as area under the ROC with 5th and 95th percentile was 0.57(0.5–0.67) with sensitivity and specificity of 0.59(0.42–0.76) and 0.57(0.45–0.7), respectively suggesting limited usefulness of 13 nucleosides/creatinine urine concentration measurements in predicting disease in this population.ConclusionBayesian multilevel pharmacokinetics-driven modeling in metabolomics may be useful in understanding the data and may constitute a new tool for searching towards potential candidates of disease indicators.

Reagent- and separation-free measurements of urine creatinine concentration using stamping surface enhanced Raman scattering (S-SERS).

We report a novel reagent- and separation-free method for urine creatinine concentration measurement using stamping surface enhanced Raman scattering (S-SERS) technique with nanoporous gold disk (NPGD) plasmonic substrates, a label-free, multiplexed molecular sensing and imaging technique recently developed by us. The performance of this new technology is evaluated by the detection and quantification of creatinine spiked in three different liquids: creatinine in water, mixture of creatinine and urea in water, and creatinine in artificial urine within physiologically relevant concentration ranges. Moreover, the potential application of our method is demonstrated by creatinine concentration measurements in urine samples collected from a mouse model of nephritis. The limit of detection of creatinine was 13.2 nM (0.15 µg/dl) and 0.68 mg/dl in water and urine, respectively. Our method would provide an alternative tool for rapid, cost-effective, and reliable urine analysis for non-invasive diagnosis and monitoring of renal function.

Comparative study of three methods of estimation of creatinine clearance in critically ill patients

BackgroundAt the bedside, the reference method for creatinine clearance determination is based on the measurement of creatinine concentrations in urine and serum (mCrCl). Several models are available to calculate the creatinine clearance from the serum creatinine concentration. This observational survey aimed at testing the hypothesis that the proposed equations are unreliable to determine accurate creatinine clearance in patients admitted to intensive care unit (ICU). MethodCreatinine clearance was determined by the use of mCrCl. Then, we compared three equations: Cockcroft-Gault (CG), Simplified Modification of Diet in Renal Disease (MDRDs), and Chronic Kidney Disease Epidemiology (CKD-EPI) in 156 consecutive patients within the first 24hours after ICU admission. We tested the hypothesis that the three equations were equivalent. The agreement between the three equations was evaluated by linear regression and Bland and Altman analysis. ResultsBland and Altman analysis showed similar agreement between the three equations. The biases and precisions were –4.8±51, –1.3±50, and 8.2±44 for CG, MDRDs, and CKD-EPI equations, respectively (P>0.05). The precisions were similar for the three equations (P>0.05). The percentages of outliers at ±30% were 44%, 45%, and 49% for CG, MDRDs, and CKD-EPI, respectively (P>0.05). ConclusionRegarding the high percentage of outliers, the use of these equations cannot be recommended in ICU patients.

Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients with Acute Kidney Injury After High‐Dose Methotrexate Therapy

Because the incidence rate of renal impairment is 2-10% for patients treated with high-dose methotrexate and renal impairment develops in 0-12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination. Pooled analysis of efficacy data from four multicenter single-arm compassionate-use clinical trials using protocols from 1993 to 2007. Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1μmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement. Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1μmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20years (range 5weeks-84years). Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7μmol/L. At the first (median 15minutes) through the last (median 40hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5days after glucarpidase administration. Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients.

Creatinine Estimation and Interference

Sir, Creatinine is one of the most common analyte used as the indicator of glomerular filtration rate (GFR) and kidney function. In 1886, Jaffe reported a reaction of creatinine and picric acid in an alkaline medium forming complex having absorbance maxima at 520 nm. The reaction has been brought to use for the measurement of creatinine by Folin and Wu in 1919. Since then, Jaffe’s reaction has been used for estimation of creatinine in serum and urine sample. For more than 90 years, this method is in use for the measurement of creatinine concentration due to its simplicity and low cost. Creatinine is produced as the byproduct of creatine metabolism and is transported through bloodstream to the kidneys for excretion. Malfunctioning of kidney is reflected by lowering of the amount of creatinine in urine and rise of its level in blood. Creatinine levels in blood and urine also indicate the creatinine clearance, accounting for GFR. Creatinine readings indicate the total kidney GFR which is the sum of filtration rates of all functional nephrons. Early structural damage to the renal cells involving reduction in functional nephron number may not affect an individual’s total GFR as remaining renal units may perform compensatory function, enabling the kidneys to maintain kidney function temporarily even after the loss of functional tissue. Thus, creatinine/GFR may not indicate the early damage to kidney tissue. Jaffe also elaborated the interference in alkaline picrate reaction by number of organic compounds (e.g. acetone, glucose) which has been described as pseudochromogens. Still, creatinine remains the gold standard for measuring the glomerular filtration rate and kidney functioning. And Jaffe method remains the default method for estimation of creatinine. In last century, many caveats in this method were reported which we have indicated in brief in this article. Recently we have reported an interference by streptomycin (an aminoglycoside) in high doses which act as false positive in Jaffe reaction [1]. It is known from literature that aminoglycosides can be nephrotoxic and may potentially affect kidney function. If it is so, then, nephrotoxicity due to high dose of aminoglycosides (say streptomycin) can never be correctly estimated as defect in excreting out creatinine would be masked by the false positive Jaffe reaction given by streptomycin. Antibiotics like cephapirin, cefazolin, cefamandole, cephalothin, and cefoxitin have been shown to interfere with creatinine determination at various concentrations [1, 2]. Phenacemide and cephalothin may interfere either positively or negatively with the determination of creatinine by the Jaffe reaction [3] . Cephalosporin antibiotics have been shown to form non-creatinine chromogen with alkaline picrate reagent and produce false positive results for creatinine. Serum creatinine and creatinine clearance values are positively interfered by cefoxitin in the Jaffe reaction, the routine laboratory method of creatinine measurement. Both invitro and invivo analysis suggest the same [4]. Many biomolecules like bilirubin, glucose, acetone etc. are also known to interfere with the Jaffe method of creatinine estimation and therefore the method has gone through modifications [5]. To overcome the effect of interference specific enzymatic method of creatinine estimation has been also developed [6]. But in-spite of various modification of the Jaffe method and development of the specific enzymatic method for creatinine estimation, the classical alkaline picrate method remains popular in India.

Acute Azotemia as a Predictor of Mortality in Dogs and Cats

Acute kidney injury (AKI) has been shown to be a predictor of mortality in human medicine. Published studies in the veterinary literature evaluating relative changes in serum creatinine concentration as a prognostic factor are limited. To evaluate an AKI grading system based on serum creatinine concentration to determine if it correlates with outcome prediction in dogs and cats. Six hundred forty-five dogs and 209 cats that had at least 2 serum creatinine concentration measurements measured within 7 days. Retrospective study. Dogs and cats with an initial serum creatinine concentrations of ≤ 1.6 mg/dL and that had more than 1 concentration measured within 2, 3, and 7 days were placed into levels (0-2) based on absolute changes. Mortality then was determined at 30 and 90 days. Based on odds ratios calculated with a 95% confidence interval, dogs placed in level 1 within 2 days were approximately 3 times more likely to die within 90 days. Dogs placed in level 2 within 2, 3, or 7 days were approximately 3 times more likely to die within 30 or 90 days. Cats placed in level 2 within 3 or 7 days were approximately 3 times more likely to die at 30 days and 4 times more likely to die if placed in this level within 7 days. If placed in level 2 within 2 or 3 days, cats were approximately 3 times more likely to die within 90 days. Detecting increasing severity of azotemia helps predict mortality in dogs and cats.

Evaluation of factors that affect analytic variability of urine protein-to-creatinine ratio determination in dogs

To determine whether preanalytic and analytic factors affect evaluation of the urinary protein-to-creatinine (UPC) ratio in dogs. 50 canine urine samples. The UPC ratio was measured to assess the intra-assay imprecision (20 measurements within a single session), the influence of predilution (1:10, 1:20, and 1:100) for urine creatinine concentration measurement, and the effect of storage at room temperature (approx 20°C), 4°C, and -20°C. The coefficient of variation at room temperature determined with the 1:20 predilution was < 10.0%, with the highest coefficients of variation found in samples with a low protein concentration or low urine specific gravity. This variability could result in misclassification of samples with UPC ratios close to the thresholds defined by the International Renal Interest Society to classify dogs as nonproteinuric (0.2), borderline proteinuric (0.21 to 0.50), or proteinuric (> 0.51). A proportional bias was found in samples prediluted 1:10, compared with samples prediluted 1:20 or 1:100. At room temperature, the UPC ratio did not significantly increase after 2 and 4 hours. After 12 hours at room temperature and at 4°C, the UPC ratio significantly increased. The UPC ratio did not significantly change during 3 months of storage at -20°C. The intra-assay precision of the UPC ratio was sufficiently low to avoid misclassification of samples, except for values close to 0.2 or 0.5. The optimal predilution ratio for urine creatinine concentration measurement was 1:20. A 1:100 predilution is recommended in samples with a urine specific gravity > 1.030. The UPC ratio must be measured as soon as samples are collected. Alternatively, samples should be immediately frozen to increase their stability and minimize the risk of misclassification of proteinuria.

Ethnic variation in the correlation between random serum glucose concentration and glycated haemoglobin

To determine if the relationship between serum glucose concentration and glycated haemoglobin is different between African-Americans and whites. Retrospective cross-sectional study comparing the association between glycated haemoglobin and serum glucose levels, based upon ethnicity. Two databases were evaluated: (i) 4215 African-American and 6359 white outpatients who had simultaneous glycated haemoglobin, random serum glucose and creatinine concentration measurements between 2000 and 2007 at the North Carolina Baptist Hospital and (ii) 1021 white and 312 African-American Diabetes Heart Study (DHS) participants. In North Carolina Baptist Hospital clinic attendees, a given glycated haemoglobin was associated with higher serum glucose concentrations in African-Americans compared with whites. In a multivariate model with glycated haemoglobin as the outcome variable, racial differences remained significant after adjustment for serum glucose, age, gender and kidney function. For individuals with a serum glucose between 5.6 and 8.3 mmol/l, the glucose : glycated haemoglobin ratio was 1.03 +/- 0.16 mmol/l/% in white individuals and 0.99 +/- 0.17 mmol/l/% in African-Americans (P < 0.0001). For a glycated haemoglobin value of 7.0%, there was a 0.98-mmol/l difference in predicted serum glucose concentration in 50-year-old African-American men, relative to white. Results were replicated in the DHS, where in a best-fit linear model, after adjustment for glucose, African-American race was a significant predictor of glycated haemoglobin (P < 0.0001). African-Americans have higher glycated haemoglobin values at given serum glucose concentrations relative to whites. This finding may contribute to the observed difference in glycated haemoglobin values reported between these race groups.

Implementation of the routine reporting of eGFR in Australia and New Zealand

The reporting of an eGFR (estimated glomerular filtration rate) with every requested serum creatinine concentration measurement has been successfully introduced as routine practice in Australia and New Zealand. This change in laboratory practice has been linked with a major educational initiative in the diagnosis and management of chronic kidney disease as well as standardization of a range of laboratory measurement and reporting issues. The process has been collaborative between renal physicians, chemical pathologists and laboratory scientists and their respective professional bodies, and the relevant decisions have been made collectively on the best available evidence. The initial guidelines were released in August 2005 and these have been followed up in 2007 with further recommendations to address issues arising since that time.

Enzymatic assays for creatinine: Time for action

Estimation of glomerular filtration rate (eGFR) on the basis of serum creatinine concentration measurements using equations is critical to ongoing global public health efforts to improve the diagnosis and treatment of chronic kidney disease. There is now ongoing activity to promote world‐wide standardization of methods to measure creatinine concentrations, together with the introduction of a revised eGFR equation appropriate for use with standardized creatinine methods. Standardization of calibration, i.e. implementation of calibration traceable to higher‐order reference measurement procedures and reference materials, does not, however, correct for analytical interferences of field methods (non‐specificity bias). To account for the sensitivity of alkaline picrate‐based methods to non‐creatinine chromogens, some manufacturers have adjusted the calibration to minimize the pseudo‐creatinine contribution of plasma proteins, thereby producing results more closely aligned with the reference method (isotope dilution‐mass spectrometry), but this strategy makes the assumption that the non‐creatinine chromogen interference is constant among samples, which is an oversimplification. Thus, analytical non‐specificity for substances found in individual patient samples affects the accuracy of eGFR computed from serum creatinine concentrations for any alkaline picrate method, including the so‐called “compensated” Jaffe methods. Using assays that are more specific for serum creatinine, such as those based on enzymatic reactions, may provide more reliable eGFR values. Supporting the choice of more specific assays by clinical laboratories is one of the main tasks of our profession in achieving the ultimate clinical goal, which is to routinely report an accurate eGFR in all pertinent clinical situations.

New creatinine sensor for point-of-care testing of creatinine meets the National Kidney Disease Education Program guidelines

Addition of the measurement of creatinine concentration in whole blood on the ABL837 FLEX blood gas analyzer (Radiometer Medical ApS, Copenhagen, Denmark) allows fast and reliable reporting of creatinine in point-of-care testing (POCT). The new creatinine sensor follows the international recommendations of the National Kidney Disease Education Program Laboratory Working Group as of January 2006 with respect to acceptable performance, reference method and traceability. Validation tests show that the creatinine sensor has excellent performance and thus has the potential to change the poor track record of creatinine testing in plasma and whole blood in both the clinical laboratory and POCT. This article describes the clinical needs and the methods currently available for creatinine measurement and presents performance tests carried out by the manufacturer.