Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms.

BACKGROUND: Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation. METHODS: Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. RESULTS: Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone). CONCLUSIONS: We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.

A study examining the bias of albumin and albumin/creatinine ratio measurements in urine.

BACKGROUND: The objective of the study was to examine the bias of albumin and albumin/creatinine (ACR) measurements in urine. METHODS: Pools of normal human urine were augmented with purified human serum albumin to generate a series of 12 samples covering the clinical range of interest for the measurement of ACR. Albumin and creatinine concentrations in these samples were analyzed three times on each of 3 days by 24 accredited laboratories in Canada and the USA. Reference values (RV) for albumin measurements were assigned by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) comparative method and gravimetrically. Ten random urine samples (check samples) were analyzed as singlets and albumin and ACR values reported according to the routine practices of each laboratory. RESULTS: Augmented urine pools were shown to be commutable. Gravimetrically assigned target values were corrected for the presence of endogenous albumin using the LC-MS/MS comparative method. There was excellent agreement between the RVs as assigned by these two methods. All laboratory medians demonstrated a negative bias for the measurement of albumin in urine over the concentration range examined. The magnitude of this bias tended to decrease with increasing albumin concentrations. At baseline, only 10% of the patient ACR values met a performance limit of RV ± 15%. This increased to 84% and 86% following post-analytical correction for albumin and creatinine calibration bias, respectively. CONCLUSIONS: International organizations should take a leading role in the standardization of albumin measurements in urine. In the interim, accuracy based urine quality control samples may be used by clinical laboratories for monitoring the accuracy of their urinary albumin measurements.

Influence of physical properties of cuvette surface on measurement of serum lipase.

BACKGROUND: Despite striking similarities among colorimetric lipase assay recipes, marked intervendor differences are noted in the reported lipase values. In the present study, the effect of physical properties of the cuvette surface on measurement of serum lipase was investigated. METHODS: Lipase activity was measured concomitantly in cuvettes from three different analyzers: Vista (Siemens), Modular (Roche), and Synchron (Beckman Coulter). The surface/volume ratio of the cuvettes and the contact angle of the cuvette polymers were determined. The effects of various characteristics of serum (biochemical parameters, surface tension) were also examined. RESULTS: Serum lipase activities based on the colorimetric methylresorufin assay differed markedly according to the cuvettes used. More specifically, in the lower activity rate, marked differences were reported. The physical properties of the various cuvettes showed remarkable differences, especially in the contact angles. Other biochemical parameters (bilirubin, alkaline phosphatase, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) and serum surface tension did not affect the results. CONCLUSIONS: Serum lipase activity is affected by the physical properties of the cuvette surface.

Performance of StatSensor Point-of-Care Device for Measuring Creatinine in Patients With Chronic Kidney Disease and Postkidney Transplantation.

BACKGROUND: The StatSensor is a point-of-care device which measures creatinine in capillary whole blood. Previous studies reported an underestimation of the creatinine measurements at high creatinine concentrations and were performed in the prestandardization era for creatinine. OBJECTIVE: This accuracy-based study evaluates the use of this device in kidney-transplanted patients and those with chronic kidney disease (CKD). DESIGN: Cross-sectional diagnostic accuracy study. SETTING: Nephrology outpatient clinic in an urban tertiary center. PARTICIPANTS: Adults with CKD or a functioning kidney transplant. MEASUREMENTS: Duplicate StatSensor creatinine measurements were performed on capillary whole blood samples collected by direct fingerstick and SAFE-T-FILL collection device. Results were compared with simultaneous venous blood sampling for serum and plasma creatinine measured by an enzymatic method on the Roche Integra 400 mainframe analyzer with traceability to the ID-GC-MS (isotope dilution gas chromatography mass spectrometry) reference method. METHODS: Deming regression, Pearson correlation coefficient, and Bland-Altman analysis were used to assess accuracy and comparability between capillary whole blood measured by StatSensor and plasma creatinine measured by routine analyzer with traceability to the reference method. Estimated glomerular filtration (eGFR) rates were calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and concordance with Kidney Disease Improving Global Outcomes (KDIGO) CKD stage classification was evaluated. RESULTS: There were 60 participants (mean age = 61.9 ± 15.0 years, 55% men, 33% transplant, mean plasma creatinine = 137 ± 59 µmol/L). Bland-Altman analysis indicated a positive mean bias of 12.7 µmol/L between StatSensor fingerstick creatinine measurement and plasma creatinine. Comparison of eGFR (CKD-EPI) calculated from the StatSensor fingerstick creatinine versus plasma creatinine showed misclassification across all KDIGO CKD stages. Postanalytical correction of the bias did not improve misclassifications. The use of mean of duplicate StatSensor creatinine results did not improve performance compared with the use of singlet results. LIMITATIONS: Single center, limited participant numbers. CONCLUSIONS: The results of our study suggest that the limiting characteristics of the StatSensor device are not only bias, but also imprecision. The level of imprecision observed may influence clinical decision-making and limit the usefulness of StatSensor as a CKD screening tool. If choosing to utilize it for either screening for or monitoring CKD, it is essential that clinicians understand the limitations of point-of-care devices and apply this knowledge to test interpretation.

CONTEXTE: Le StatSensor est un appareil portatif conçu pour mesurer le taux de créatinine dans le sang capillaire total. Des études antérieures, réalisées avant la standardisation des mesures de la créatinine, ont rapporté une sous-estimation des mesures à des concentrations élevées. OBJECTIF: Cette étude centrée sur la précision a examiné l'utilisation de cet appareil chez des patients transplantés d'un rein et des patients atteints d'insuffisance rénale chronique (IRC). TYPE D'ÉTUDE: Étude transversale centrée sur la précision du diagnostic. CADRE: La clinique ambulatoire de néphrologie d'un centre de soins tertiaires en milieu urbain. SUJETS: Des adultes atteints d'IRC ou transplantés avec un rein fonctionnel. MESURES: Les mesures de créatinine par StatSensor ont été effectuées en double sur des échantillons de sang capillaire total prélevés par ponction digitale directe et à l'aide du dispositif de prélèvement SAFE-T-FILL. Ces résultats ont été comparés à un prélèvement veineux simultané pour la mesure des taux de créatinine sérique et plasmatique par la méthode enzymatique avec l'analyseur Integra 400 de Roche avec traçabilité à la méthode de référence ID-GC-MS. MÉTHODOLOGIE: La régression de Deming, le coefficient de corrélation de Pearson et l'analyse de Bland-Altman ont été utilisés pour évaluer la précision et la comparabilité entre les mesures du sang capillaire total par StatSensor et la mesure de créatinine plasmatique obtenue par l'analyseur de routine avec traçabilité à la méthode de référence. Le débit de filtration glomérulaire estimé (DFGe) a été calculé avec l'équation CKD-EPI, puis la concordance avec la classification des stades KDIGO pour l'IRC a été évaluée. RÉSULTATS: L'étude a inclus 60 patients (55 % d'hommes; âge moyen 61,9 ± 15,0 ans) dont 33 % étaient transplantés. Le taux moyen de créatinine plasmatique s'établissait à 137 ± 59 µmol/L. L'analyse de Bland-Altman indique un biais positif moyen de 12,7 µmol/L entre la mesure de créatinine obtenue avec StatSensor par ponction digitale et le taux de créatinine plasmatique. La comparaison entre le DFGe (CKD-EPI) calculé à partir des mesures obtenues par ponction digitale avec StatSensor et de la mesure de créatinine plasmatique a montré une classification erronée à tous les stades KDIGO pour l'IRC. La correction du biais après l'analyse n'a pas amélioré les erreurs de classification. L'utilisation de la moyenne des résultats obtenus par StatSensor sur les échantillons prélevés en double n'a pas amélioré les performances par rapport à l'utilisation de singulets. LIMITES: Étude monocentrique, nombre de participants limité. CONCLUSION: Nos résultats suggèrent que les caractéristiques de limitation du StatSensor ne constituent pas qu'un biais, mais également une imprécision. Ce degré d'imprécision peut influencer la prise de décision clinique et limiter l'utilité du StatSensor comme outil de dépistage de l'IRC. Il est essentiel que les cliniciens soient conscients des limites de ces dispositifs et qu'ils appliquent ces connaissances à l'interprétation des résultats s'ils choisissent de les utiliser pour dépister ou surveiller l'IRC. ENREGISTREMENT DE L'ESSAI: Sans objet, il ne s'agissait pas d'un essai clinique.

Current issues in measurement and reporting of urinary albumin excretion.

BACKGROUND: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement. CONTENT: The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion. DISCUSSION: Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.

Regional implementation of creatinine measurement standardization.

Because patients may receive care at multiple locations within a geographic area, serum creatinine measurements must be standardized across laboratories to enable comparisons of reported estimated glomerular filtration rate (eGFR). The results of a successful creatinine standardization program designed to minimize the contribution of laboratory error to the reporting of eGFR are reported; 107 laboratories, which tested creatinine on 124 analyzers from six different manufacturers, voluntarily participated. Each laboratory received a correction factor to apply to its creatinine measurements to standardize them to the isotope dilution mass spectrometry reference method. The adjusted values were then used to calculate eGFR using the Modification of Diet in Renal Disease (MDRD) equation. The standardization program reduced the average total error in the measurement of creatinine from 23.9 to 8.7% and the average analytical bias from 16.5 to 2.7%. Implementing this program on a larger scale could reduce the rate of incorrect classification of stage 3 chronic kidney disease by 84%.

A Summary of Worldwide National Activities in Chronic Kidney Disease (CKD) Testing.

Chronic kidney disease (CKD) is a major public health issue worldwide and is associated with adverse health outcomes, especially in low- and middle-income countries. In a cash limited healthcare system, guidelines that improve the efficiency of health care free up resources needed for other healthcare services. This short review presents some examples from national acitivities in CKD testing, including countries throughout the globe: Mexico in North America, Uruguay in South America, Italy in Europe, Nigeria in Africa and India in Asia. Considering the fact that treatment of CKD is cost-effective and improves outcomes, this observation argue in favor of including CKD in national guidelines and noncommunicable chronic disease (NCD) programs. This diverse example of national activities fullfil the very first step in achieving this goal.

National Survey of Adult and Pediatric Reference Intervals in Clinical Laboratories across Canada: A Report of the CSCC Working Group on Reference Interval Harmonization.

OBJECTIVE: Reference intervals are widely used decision-making tools in laboratory medicine, serving as health-associated standards to interpret laboratory test results. Numerous studies have shown wide variation in reference intervals, even between laboratories using assays from the same manufacturer. Lack of consistency in either sample measurement or reference intervals across laboratories challenges the expectation of standardized patient care regardless of testing location. Here, we present data from a national survey conducted by the Canadian Society of Clinical Chemists (CSCC) Reference Interval Harmonization (hRI) Working Group that examines variation in laboratory reference sample measurements, as well as pediatric and adult reference intervals currently used in clinical practice across Canada. DESIGN AND METHODS: Data on reference intervals currently used by 37 laboratories were collected through a national survey to examine the variation in reference intervals for seven common laboratory tests. Additionally, 40 clinical laboratories participated in a baseline assessment by measuring six analytes in a reference sample. RESULTS: Of the seven analytes examined, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatinine reference intervals were most variable. As expected, reference interval variation was more substantial in the pediatric population and varied between laboratories using the same instrumentation. Reference sample results differed between laboratories, particularly for ALT and free thyroxine (FT4). Reference interval variation was greater than test result variation for the majority of analytes. CONCLUSION: It is evident that there is a critical lack of harmonization in laboratory reference intervals, particularly for the pediatric population. Furthermore, the observed variation in reference intervals across instruments cannot be explained by the bias between the results obtained on instruments by different manufacturers.

Agreement of Point-of-Care Capillary Glycated Hemoglobin Levels with Conventional Screening Tests for Diabetes Mellitus in a Canadian First Nations Population.

OBJECTIVES: 1) How closely do capillary glycated hemoglobin (A1C) levels agree with venous A1C levels? 2) How well do venous A1C levels agree with plasma glucose for diagnosis of diabetes in this population? METHODS: The Seabird Island mobile diabetes clinic screened people not known to have diabetes by using finger-prick capillary A1C levels with point-of-care analysis according to the Siemens/Bayer DCA 2000 system. Clients then went to a clinical laboratory for confirmatory testing for venous A1C levels, fasting plasma glucose (FPG) and plasma glucose 2 hours after 75 g oral glucose load (2hPG). A reference laboratory compared the DCA 2000 and the clinical laboratory's Roche Integra 800CTS system to the National Glycohemoglobin Standardization Program Diabetes Control and Complications Trial (DCCT) reference. RESULTS: 1) In the reference laboratory, DCA 2000 and Integra 800CTS both agreed very closely with the DCCT standard. In the field, capillary glycated hemoglobin percent (A1C) % was biased, underestimating venous A1C % by a mean of 0.19 (p<0.001). The margin of error of bias-adjusted capillary A1C % was ±0.36 for 95% of the time, compared to ±0.27 for venous A1C%. 2) By linear regression, we found FPG 7.0 mmol/L and 2hPG 11.1 mmol/L predicted mean venous A1C levels very close to 6.5%, with no significant bias. CONCLUSIONS: Point-of-care capillary A1C did not perform as well in the field as in the laboratory, but the bias is correctible, and the margin of error is small enough that the test is clinically useful. In this population, venous A1C levels ≥6.5% agree closely with the FPG and 2hPG thresholds to diagnose diabetes; ethnic-specific adjustment of the venous A1C threshold is not necessary.

Hypertriglyceridemic hyperapoB in type 2 diabetes.

OBJECTIVES: Much less attention has been paid to LDL in type 2 diabetes than to VLDL or HDL. In particular, there are few data on apoB levels in these patients. Moreover, most reports have focused on mean lipoprotein levels and consequently there is little information on the frequencies of the various dyslipidemic phenotypes. RESEARCH DESIGN AND METHODS: Plasma and lipoprotein lipids, apoB and apoA1 were measured by standardized methods. LDL particle size was determined by PAGE. The total cohort was divided into phenotypes by two different methods. The first was based on triglycerides (> or = or <1.5 mmol/l) and LDL cholesterol (> or = or <4 mmol/l), whereas the second was based on triglycerides (> or = or <1.5 mmol/l) and apoB (> or = or <120 mg/dl). RESULTS: For the overall cohort, plasma triglycerides were elevated (2.13 +/- 1.6 mmol/l), total and LDL cholesterol were normal (5.34 +/- 1.1 and 3.28 +/- 0.88 mmol/l, respectively), and peak LDL size was reduced (252.9 +/- 5.8 A). HDL cholesterol was between the 25th and 50th percentiles of the general population (1.12 +/- 0.36 mmol/l). The average level of apoB was 114 +/- 29 mg/dl, a value that is between the 50th and 75th percentiles of the general population and is higher than that for LDL cholesterol, which was between the 25th and the 50th percentiles of the population. The results of the phenotyping analysis were as follows. Using the conventional approach, only 23% has abnormal LDL, i.e., an elevated LDL cholesterol level. Using the new approach, almost 40% has an elevated apoB and therefore an elevated LDL particle number. Only 12.8% has combined hyperlipidemia based on the conventional approach, whereas almost one-third had the equivalent, hypertriglyceridemic hyperapoB-based on the new algorithm. The severity of the dyslipoproteinemia in this group was noteworthy. Although the average LDL cholesterol was 3.91 mmol/l, a value just below the 75th percentile of the general population, the average apoB was 145 mg/dl, a value that approximates the 95th percentile of the population. CONCLUSIONS: The dyslipidemic profile of patients with type 2 diabetes is not uniform. A substantial group have normal lipids and normal LDL particle number and size whereas others have markedly abnormal profiles. Diagnosis based on triglycerides and apoB rather than triglycerides and LDL cholesterol revealed that more than one in five had hypertriglyceridemic hyperapoB, which is characterized by hypertriglyceridemia, marked elevation of LDL particle number, small dense LDL, and low HDL, a constellation of abnormalities that is associated with markedly accelerated atherogenesis and therefore justifies intensive medical therapy.

Effect of cyclosporine A on the binding affinity and internalization of low-density lipoproteins in human skin fibroblasts.

The aim of this study was to elucidate the possible causes of elevated low-density lipoprotein (LDL)-cholesterol levels in patients with transplants who were treated with the immunosuppressant drug cyclosporine A (CSA). The binding and internalization of (125)I-LDL in the presence or absence of CSA at varying concentrations (5-15 microg/mL) within human skin fibroblasts were determined. In addition, the effect of LDL-associated CSA on the binding of LDL to its receptor was determined. CSA decreases LDL internalization without altering the extent and affinity of its binding to the LDL receptor. CSA did not alter the number of available LDL binding sites. Furthermore, the association of CSA with LDL did not affect the binding affinity of LDL to its receptor, suggesting that this binding may not be a mechanism by which CSA affects the subsequent clearance of LDL from the bloodstream. These findings suggest that CSA may cause an increase in plasma LDL-cholesterol in patients with transplants, thereby inhibiting LDL particle internalization without altering LDL receptor binding.

Evaluation of a mobile diabetes care telemedicine clinic serving Aboriginal communities in Northern British Columbia, Canada.

INTRODUCTION: In British Columbia, Aboriginal diabetes prevalence, hospitalization and mortality rates are all more than twice as high as in the rest of the population. We describe and evaluate a program to improve access to diabetes care for Aboriginal people in northern communities. STUDY DESIGN: Cost-effectiveness evaluation. METHODS: A diabetes nurse educator and an ophthalmic technician travel to Aboriginal reserves, offering people with diabetes services recommended in current clinical practice guidelines: retinopathy screening by digital retinal fundus photography, glaucoma screening by tonometry, point-of-care urine and blood testing to detect microalbuminuria and dyslipidemia and to measure glycated hemoglobin, foot examinations and foot care advice, blood pressure and height and weight measurement and diabetes care advice. Via electronic communication, an ophthalmologist and an endocrinologist in Vancouver review the findings and supervise the mobile clinic staff. RESULTS: During the first year, 25 clinics were held at 22 sites, examining 339 clients with diabetes. Exit surveys showed high levels of client satisfaction. Mean cost per client (Cdn dollars 1,231) was less than for the alternative, transporting clients to care in the nearest cities (Cdn dollars 1,437). CONCLUSIONS: The mobile clinic is cost-effective and improves access to the recommended standard of diabetes care.

CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort.

OBJECTIVES: The CALIPER program recently established a comprehensive database of age- and sex-stratified pediatric reference intervals for 40 biochemical markers. However, this database was only directly applicable for Abbott ARCHITECT assays. We therefore sought to expand the scope of this database to biochemical assays from other major manufacturers, allowing for a much wider application of the CALIPER database. DESIGN AND METHODS: Based on CLSI C28-A3 and EP9-A2 guidelines, CALIPER reference intervals were transferred (using specific statistical criteria) to assays performed on four other commonly used clinical chemistry platforms including Beckman Coulter DxC800, Ortho Vitros 5600, Roche Cobas 6000, and Siemens Vista 1500. The resulting reference intervals were subjected to a thorough validation using 100 reference specimens (healthy community children and adolescents) from the CALIPER bio-bank, and all testing centers participated in an external quality assessment (EQA) evaluation. RESULTS: In general, the transferred pediatric reference intervals were similar to those established in our previous study. However, assay-specific differences in reference limits were observed for many analytes, and in some instances were considerable. The results of the EQA evaluation generally mimicked the similarities and differences in reference limits among the five manufacturers' assays. In addition, the majority of transferred reference intervals were validated through the analysis of CALIPER reference samples. CONCLUSIONS: This study greatly extends the utility of the CALIPER reference interval database which is now directly applicable for assays performed on five major analytical platforms in clinical use, and should permit the worldwide application of CALIPER pediatric reference intervals.

Establishing reference intervals for clinical laboratory test results: is there a better way?

Reference intervals are essential for clinical laboratory test interpretation and patient care. Methods for estimating them are expensive, difficult to perform, often inaccurate, and nonreproducible. A computerized indirect Hoffmann method was studied for accuracy and reproducibility. The study used data collected retrospectively for 5 analytes without exclusions and filtering from a nationwide chain of clinical reference laboratories in the United States. The accuracy was assessed by the comparability of reference intervals as calculated by the new method with published peer-reviewed studies, and reproducibility was assessed by the comparability of 2 sets of reference intervals derived from 2 different data sets. There was no statistically significant difference between the calculated and published reference intervals or between the 2 sets of intervals that were derived from different data sets. A computerized Hoffmann method for indirect estimation of reference intervals using stored test results is proved to be accurate and reproducible.

State of the art in trueness and interlaboratory harmonization for 10 analytes in general clinical chemistry.

CONTEXT: Harmonization and standardization of results among different clinical laboratories is necessary for clinical practice guidelines to be established. OBJECTIVE: To evaluate the state of the art in measuring 10 routine chemistry analytes. DESIGN: A specimen prepared as off-the-clot pooled sera and 4 conventionally prepared specimens were sent to participants in the College of American Pathologists Chemistry Survey. Analyte concentrations were assigned by reference measurement procedures. PARTICIPANTS: Approximately 6000 clinical laboratories. RESULTS: For glucose, iron, potassium, and uric acid, more than 87.5% of peer groups meet the desirable bias goals based on biologic variability criteria. The remaining 6 analytes had less than 52% of peer groups that met the desirable bias criteria. CONCLUSIONS: Routine measurement procedures for some analytes had acceptable traceability to reference systems. Conventionally prepared proficiency testing specimens were not adequately commutable with a fresh frozen specimen to be used to evaluate trueness of methods compared with a reference measurement procedure.

Estimating pediatric glomerular filtration rates in the era of chronic kidney disease staging.

With the use of information from a database of pediatric patients with concomitant nuclear GFR and serum creatinine (Cr), estimated GFR equations were derived on the basis of local laboratory methods and population. These formulas then were compared with those recommended by the National Kidney Foundation for estimating GFR in children. For this, their ability to estimate accurately an individual's true GFR and chronic kidney disease stage, identify patients whose true GFR was <60 ml/min per 1.73 m(2), and to identify correctly deterioration in an individual's GFR over time was compared. Next, two methods to estimate GFR in children without the use of height or weight were developed. The first was a height- and weight-independent formula; the second was a novel approach using the Schwartz formula and calculating a Cr cutoff based on age-based estimates of height and GFR level of interest, i.e., <60 ml/min per 1.73 m(2). Our results suggest that if local laboratory constants are derived and a height is known, then the Schwartz formula offers the most accuracy with least mathematical complexity to perform in the clinical setting. If height is not available but the local laboratory constants have been derived, then the British Columbia's Children's Hospital 2 formula is of value; however, in the setting of estimating pediatric renal function in the outpatient laboratory, where neither of these factors is commonly known, an approach whereby a Cr cutoff for a GFR of interest is developed is suggested. Provided are Cr levels that are based on a reference method of Cr measurement to facilitate this approach for the clinician.

Questões atuais relativas à dosagem e à descrição da excreção urinária de albumina / Current issues in measurement and report of urinary albumin excretion

ANTECEDENTES: A excreção urinária de albumina indica lesão nos rins e é reconhecida como fator de risco para a progressão das doenças renal e cardiovascular. A dosagem da albumina urinária chama a atenção sobre a necessidade clínica de relatos de resultados precisos e claramente descritos. O National Kidney Disease Education Program e a Federação Internacional de Química Clínica e Medicina Laboratorial (IFCC) reuniram-se para avaliar o estado atual das questões pré-analíticas, analíticas e pós-analíticas que afetam as dosagens da albumina na urina e para identificar as áreas que necessitam de melhorias. CONTEÚDO: A química da albumina na urina não é completamente compreendida. Diretrizes atuais recomendam a utilização da relação albumina/creatinina (RAC) como substituta para a coleta de amostras cronometradas de urina, frequentemente inadequadas. Os resultados da RAC são afetados pela preparação do paciente, pela hora do dia da coleta das amostras e não é padronizada. Foram relatadas consideráveis diferenças intermétodos para a dosagem tanto de albumina quanto de creatinina, mas a verdade é desconhecida, porque não existem procedimentos de referência para a dosagem de albumina e não há materiais de referência para qualquer um desses analitos na urina. Os intervalos de referência recomendados para a RAC não consideram as grandes diferenças intergrupos na excreção da creatinina (por exemplo, relacionadas com diferenças em idade, sexo e etnia), nem o aumento contínuo no risco relacionado com a excreção de albumina. DISCUSSÃO: Necessidades clínicas foram identificadas para a padronização de (a) métodos de coleta da urina, (b) dosagens de albumina e de creatinina na urina com base em um sistema de referência completo, (c) relatórios dos resultados dos testes e (d) intervalos de referência para a RAC.

BACKGROUND: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement. CONTENT: The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion. DISCUSSION: Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.