[Macroenzymes: macro-ASAT and macro-CPK. Two cases and literature review]. / Macroenzymes : macro-ASAT et macro-CPK. Deux observations et revue de la littérature.

INTRODUCTION: Macroenzymes are high molecular weight complex formed by the binding of one enzyme and a serum macromolecule, responsible for an increase in the activity of the corresponding enzyme in blood assay. CASE REPORTS: We report two cases: firstly, a macro-aspartate aminotransferase (macro-ASAT) discovered in an 82-year-old woman who presented with an isolated and persistent elevation of the ASAT activity that was discovered after sepsis, secondly, a macro-creatine-kinase (macro-CPK) diagnosed in a 62-year-old man after several years of investigations for a persistent CPK elevation. These two case reports allowed us to discuss the mechanism leading to the formation of macroenzymes and the usefulness of their determination. Although macroenzymes are generally non pathologic, they may be associated with auto-immune, neoplastic or infectious diseases. CONCLUSION: The possibility of a macroenzyme should be entertained in the presence of an unexplained and isolated increased enzyme activity. It prevents costly and unnecessary investigations.

["Corrected" calcium: calcium status underestimation in non-hypoalbuminemic patients and in hypercalcemic patients]. / Calcémie "corrigée": sous-estimation du statut calcique des patients sans hypoalbuminémie et des patients hypercalcémiques.

It is often reminded that if the ionized calcium is not measured, the interpretation of total calcemia should consider serum albumin. Two formulas are usually employed: ["Corrected" Ca (mmol/L) = Ca measured (mmol/L) + 0.020 or 0.025 (40 - albumin (g/L))]. This adjustment formula arises from works of Payne published in 1973. In a control population, we established the median values of calcium, albumin and ionized calcium (corrected to pH 7.40), respectively 2.34 mmol/L, 45.7 g/L and 1.23 mmol/L with our laboratory's methods (albumin - bromocresol green and Ca - ortho-cresolphtalein on a Modular analyser, Roche Diagnostics; ionized calcium with ion-selective electrode, Radiometer SA). Based on this, we retrospectively compared for 71 patients who do not belong to the control population the "corrected calcium" resulting from the two formulas and the measured calcemia to the ionized calcium corrected at pH 7,40. This comparison shows that in our laboratory, the two formulas lead to a rising underestimation of the calcium for albumin values greater than 40 g/L, reaching -0,20 mmol/L for albumin values above 44 g/L. The use of this formulas may also mask an hypercalcemia, indeed half of our patients' hypercalcemia (ionised Ca ((pH 7,40)) > 1,29 mmol/L) is not found. These results agree with Payne's recommendations for the use of his adjustment formula: the clinically justified adjustment of a low calcemia due to an hypoalbuminemia should not be extended to other situations, particularly when albumin is increased.

[Consequences for clinical biochemists of the modifications of the creatinine-based evaluation of glomerular filtration rate between 2005 and 2008]. / Evolution des modalités d'évaluation de la fonction rénale basée sur la créatinine entre 2005 et 2008: conséquences pour les biologistes.

Since 2005, international guidelines propose a stadification for chronic renal failure based on the glomerular filtration rate (GFR) value. The performance of the creatinine-based equations allowing the estimation of GFR and the bias of the creatinine measurements is, more than ever, a crucial issue. The consequences for the clinical biologists are of importance. First, the Cockcroft-Gault formula must be replaced by the four variable-MDRD equation. Second, the biologists must chose from the "175" and the "186" versions of the MDRD equation. The first one fits the creatinine methods which are traceable to the reference method (liquid or gas chromatography coupled to mass spectrometry). The second equation must be used for creatinine methods, which are not traceable to the reference method. Today, only some enzymatic methods can prove that they are traceable to the reference method. For the colorimetric methods, future is inclear.

[Improving the interlaboratory variation for creatinine serum assay]. / Dosage de la créatininémie en 20003: état des lieux analytique et essai de standardisation de l'étalonnage.

PURPOSE: To assess inter-assay variation and accuracy of blood creatinine measurements as well as the effect of the standardization of the calibration procedures on inter-assay variation. METHODS: Inter-assay variation and accuracy were assessed using 30 frozen human sera and 3 certified reference materials, which were analysed by 17 creatinine assays (colorimetric: 12, enzymatic: 4, HPLC: 1). Usual calibration procedure was compared with two common calibration procedures using either a reference material (404.1 micromol/L), or secondary sera calibrators (69, 115 et 180 micromol/L). RESULTS: Most of the commercially available methods display inaccuracy, > 10% for creatininemia < 150 micromol/L in most cases. For this concentration range, the mean creatininemia was statistically significantly different as a function of the assay used (p < 0.001). Enzymatic assays produced lower results than colorimetric ones for low creatinine levels but higher results for high creatinine levels. Assays being calibrated according to the manufacturer's recommendations, the median dispersion factor was 14% for the 20 samples between 45 and 150 micromol/L, and 8% for the 10 samples between 250 and 350 micromol/L. The calibration procedure modified inter-assay variation significantly (p < 0.001) but we gained little advantage from both common calibration procedures. A significant decrease of inter-assay variation occurred within each technical group (colorimetric or enzymatic) when a common calibration was performed using calibrators which concentration(s) was(were) close to the concentrations to be measured. CONCLUSIONS: Inter-assay variation is too high to allow prediction of glomerular filtration rate (GFR) or creatinine clearance from serum creatinine level. Our results highlight the interest of a calibration procedure using several concentrations with at least one between 90 and 150 micromol/L. The marketing of such a calibrator should be considered in order to decrease inter-assay variation in the range of creatinine levels which defines a mild chronic renal failure. Such an approach will certainly reduce inter-assay variation only within each technical group but could allow to include technical group as a co-variable in the algorithms developed for predicting GFR or creatinine clearance. A global transferability will certainly need the correlation of all types of creatinine assays versus a definitive method, whom definition remains uncertain.

[Comparison of methods for the determination of blood creatinine]. / Comparison des méthodes de dosage de la créatinine sérique.

Creatinine is the criterion the most widely used for kidney exploration, either directly or through algorithms. Up to now, it appears that methods of creatinine determination are still very heterogenous. The aim of the present study was to compare the different available methods and to evaluate their impact on the formula of predicted clearance. The study revealed that significant discrepancies can be observed depending on the methodology and analitycal principe. The results suggest that standardization of methods and comprehensive analysis of the different formula are necessary.