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.

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.

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.

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.

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.

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.

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.

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.