Michael Peake

Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: new developments and revised recommendations

The publication of the Australasian Creatinine Consensus Working Groups position statements in 2005 and 2007 resulted in automatic reporting of estimated glomerular filtration rate (eGFR) with requests for serum creatinine concentration in adults, facilitated the unification of units of measurement for creatinine and eGFR, and promoted the standardisation of assays. New advancements and continuing debate led the Australasian Creatinine Consensus Working Group to reconvene in 2010. The working group recommends that the method of calculating eGFR should be changed to the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formula, and that all laboratories should report eGFR values as a precise figure to at least 90 mL/min/1.73 m2. Age‐related decision points for eGFR in adults are not recommended, as although an eGFR < 60 mL/min/1.73 m2 is very common in older people, it is nevertheless predictive of significantly increased risks of adverse clinical outcomes, and should not be considered a normal part of ageing. If using eGFR for drug dosing, body size should be considered, in addition to referring to the approved product information. For drugs with a narrow therapeutic index, therapeutic drug monitoring or a valid marker of drug effect should be used to individualise dosing. The CKD‐EPI formula has been validated as a tool to estimate GFR in some populations of non‐European ancestry living in Western countries. Pending publication of validation studies, the working group also recommends that Australasian laboratories continue to automatically report eGFR in Aboriginal and Torres Strait Islander peoples. The working group concluded that routine calculation of eGFR is not recommended in children and youth, or in pregnant women. Serum creatinine concentration (preferably using an enzymatic assay for paediatric patients) should remain as the standard test for kidney function in these populations.

Assessment of the Nova StatSensor whole blood point-of-care creatinine analyzer for the measurement of kidney function in screening for chronic kidney disease

Abstract Background: Point-of-care testing for creatinine using a fingerprick sample and resultant estimated glomerular filtration rate has potential for screening for chronic kidney disease in community settings. This study assessed the applicability of the Nova StatSensor creatinine analyzer for this purpose. Methods: Fingerprick samples from 100 patients (63 renal, 37 healthy volunteers; range 46–962 μmol/L) were assayed using two StatSensor analyzers. Lithium heparin venous plasma samples collected simultaneously were assayed in duplicate using the isotope dilution mass spectrometry-aligned Roche Creatinine Plus enzymatic assay on a Hitachi Modular P unit. Method comparison statistics and the ability of the StatSensor to correctly categorise estimated glomerular filtration rate above or below 60 mL/min were calculated pre- and post-alignment with the laboratory method. Results: StatSensor 1 creatinine results (y) were much lower than the laboratory (y=0.75x+10.2, average bias –47.3, 95% limits of agreement –208 to +113 μmol/L). For estimated glomerular filtration rates above or below 60 mL/min, 100% and 87% of results respectively agreed with the laboratory estimated glomerular filtration rate (79% and 96% post-alignment). StatSensor 2 statistics were similar. The 95% limits of agreement between StatSensor creatinine results were –35 to +34 μmol/L. Conclusions: Isotope dilution mass spectrometry alignment of the StatSensor will identify most patients with estimated glomerular filtration rate <60 mL/min, but there will be many falsely low estimated glomerular filtration rate results that require laboratory validation. Creatinine results need improvement. Clin Chem Lab Med 2010;48:1113–9.

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.

It’s Time for a Better Blood Collection Tube to Improve the Reliability of Glucose Results

Glucose is unstable in whole blood (1). Fluoride-containing tubes are used to reduce glycolysis, especially when very accurate glucose results are required. Complete inhibition of glycolysis by fluoride can take as long as 4 h, during which time glucose can fall as much as 10 mg/dL (0.6 mmol/L) at room temperature (1), even in samples with normal blood cell counts. This is because fluoride inhibits the enzyme enolase, which acts late in the Embden-Meyerhof pathway, thus allowing the “breakdown” of glucose to intermediate molecules earlier in the glycolytic cycle (2). Is there a better fluoride …

Bilirubin Measured on a Blood Gas Analyser: A Suitable Alternative for Near-Patient Assessment of Neonatal Jaundice?

The reliability of a recently released total bilirubin assay for a blood gas analyser was assessed in two Australian hospital laboratories. The instrument computes total bilirubin concentration from multi-wavelength absorbance measurements of undiluted whole blood or plasma. Performance of the Radiometer ABL 735 blood gas analyser bilirubin method (software version 3.6) was compared with a proven Roche diazo method for Hitachi analysers, calibrated using primary standards prepared from NIST SRM 916a bilirubin. Acceptable bilirubin results were found over a wide concentration range for most neonatal samples of whole blood or plasma. For adult specimens, bilirubin results were approximately 10% lower on the blood gas analyser. Within-run imprecision (whole blood) was <2·5%, between-day imprecision (synthetic controls) <1·0%, and the bilirubin assay for both whole blood and plasma was linear to 1000μmol/L. Using sampling options from 35 μL to 195μL, bilirubin results differed by less than 3%, with a 95 μL syringe option producing the highest results. We conclude that the Radiometer ABL 735 bilirubin assay is suitable for near-patient assessment of neonatal jaundice using whole blood, thus eliminating the need for sample centrifugation. Verification using laboratory methods can be used when required. A positive correction of approximately 10% is required for adult specimens to conform with Hitachi results (SRM 916a calibration), possibly due to the optical characteristics of the higher proportion of conjugated bilirubin and other substances present in most adult samples.

Bicarbonate Interference with Hitachi Chloride Electrodes

The Hitachi 7 17 is a random access analyser with an optional Ion Selective Electrode (ISE) unit for measuring sodium, potassium and chloride. On an earlier instrument, the Hitachi 705, bicarbonate ions have been reported to have a substantial influence on chloride results, ‘each millimole of bicarbonate per litre contributing approximately 0.5 mmol/L to the apparent chloride concentration’.’ These authors conclude that ‘the chloride ISE is totally unsuitable for clinical analyses pending a significant improvement in selectivity’. In the following case study, we illustrate why the reliability of Hitachi 717 chloride electrodes should also be carefully assessed for acute care patients with abnormal plasma bicarbonate concentrations.

Theoretical constraints in the measurement of serum bilirubin binding capacity

The large majority of methods for measuring serum unoccupied bilirubin binding capacity involve adding an exogenous ligand to a diluted serum sample. If the added ligand binds specifically to bilirubin binding sites, the extrapolation is made that the amount of ligand which becomes bound represents the previously unoccupied bilirubin binding capacity of the original sample. This simple theory ignores the labile nature of the equilibrium reactions between bilirubin binding sites and the ligands with which they interact. The present theoretical and experimental study of these equilibrium reactions shows that (a) sample dilution alone results in changes in the proportional occupancy of bilirubin binding sites by bilirubin and other endogenous ligands, so that the extent of vacancy of those binding sites becomes exaggerated; (b) addition of an exogenous ligand to the diluted sample results is further displacement of native bilirubin and other endogenous ligands from bilirubin binding sites. The amount of added ligand which becomes bound is thus likely to represent a greater extent of vacancy of bilirubin binding sites than was present in the original sample. Results from such methods can therefore only overestimate the unoccupied bilirubin binding capacity of blood plasma in vivo. In order to avoid these analytical problems, current methods must be redesigned. It is suggested from this work that the ability of a serum to sequester safety additional bilirubin may best be assessed from measurement of its bilirubin buffering capacity. This parameter is different from the total or unoccupied binding capacity currently attempted, and its measurement is within the capability of published methods for measuring free (= unbound) bilirubin, modified to analyse minimally diluted samples.

Comparison of standardization techniques for manual colorimetric analyses

The influence of both the mode of standardization and the type of standard on the precision of four manual colorimetric methods performed under optimal conditions variance is described. The terms variable calibration mode and constant calibration mode are proposed; these describe standardization by within-run standards and standardization by a predetermined calibration relationship between concentration and absorbance that remains constant over a fixed period of time. We show that calibration relationships and mode of standardization must be established for each and every individual method on objective evidence. Where within-run standards are used, they must be carefully selected for each method. The implications for method evaluation and quality control are discussed.

Arterial Blood Gas Analysis: Selecting the Clinically Appropriate Option for Calculating Base Excess

As part of arterial blood gas analysis, base excess is often reported as a measure of non-respiratory acid-base disturbance. Most blood gas analysers offer the option of calculating either the base excess of the blood sample or the base excess of the extracellular fluid (ECF). We report a case that illustrates that selecting the physiologically appropriate parameter avoids the potential for misinterpretation of acid-base data. We recommend that the base excess of the ECF is the appropriate metabolic blood gas parameter for clinical use.

The Effect of Instrument Variables on Calculation Factors for Standardisation of Colorimetric Analyses

A number of colorimetric methods, particularly enzyme activity assays, are usually standardised using calculation factors based on the molar absorptivity of a principle reactant or product. Such methods are subject to long-term variation. The relationship between long-term variation in results and instrument variables affecting calculation factors has not been quantitated. In this study, we have shown that, on a centrifugal analyser having a within-run coefficient of variation of less than 1%, instrument variables affecting calculation factor alone could result in changes in results of up to 8·5% over 75 days. We therefore advocate daily use of a solution of potassium dichromate to monitor instrument variables that can independently affect calculation factors and within-run imprecision. This procedure is useful for maintaining long-term performance and for differentiating problems of instrumental or chemical origin.