A multicentric evaluation of IDMS-traceable creatinine enzymatic assays

Abstract

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9 ± 0.9 μmol/L to 174.5 ± 3.1 μmol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4 ± 1.4 μmol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9 ± 0.9 μmol/L), the bias ranged from −1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40 μmol/L.

Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate

“…As a consequence, major improvements have been achieved in the creatinine standardization process. At present the majority of creatinine enzymatic assays are standardized to mass spectrometry and can be considered IDMS (isotope dilution mass spectrometry)-traceable [15]. To achieve the same level of standardization as for creatinine, an international standard and a reference method for accurate quantification of cysC in the standard material [16] are mandatory.…”

Adaptation posologique des médicaments et fonction rénale : quel(s) estimateur(s) faut-il choisir ?

“…Cette erreur potentielle peut influencer le biais des é quations. Thé oriquement, les mé thodes colorimé triques de Jaffe et les mé thodes enzymatiques peuvent être calibré es et standardisé es sur une valeur Isotope Dilution Mass Spectrometry (IDMS), c'est-à -dire une valeur mesuré e par spectromé trie de masse [59,62].…”

“…En pratique cependant, il apparaît que cette calibration IDMS n'est ré ellement effective que pour les techniques enzymatiques [62,63]. La pré cision intrinsè que de la mesure de la cré atinine, telle qu'elle peut être appré hendé e, entre autres, par le coefficient de variation analytique, va influencer la pré cision de la formule, et là encore on peut retrouver un avantage à utiliser les techniques enzymatiques qui sont plus performantes [59][60][61][62].…”

Estimating GFR in children

“…3,4 In 2009, Schwartz et al recalculated the k value of the estimating equation to be used with the enzymatic method and plasma iohexol clearance measurement as a reference method to assess GFR. 4 The fact that most of the enzymatic methods available in 2012 are isotope dilution mass spectrometry (IDMS)-traceable means that an identical equation can be used in all laboratories, which is very important from a practical point of view 5 However, a limitation of the 2009 study was that the equation was not validated in an independent validation cohort. In the same publication, the researchers studied the performance of the new renal biomarker cystatin C. In contrast to prior studies, Schwartz and colleagues demonstrated that cystatin C was less predictive of measured GFR than was height/serum creatinine, which resulted in a less powerful cystatin C exponent in the final equation compared with height/serum creatinine.…”

“…The precision of a GFR equation will strongly depend on the analytical precision of the biological variables included (enzymatic, IDMS-traceable method for creatinine and PENIA method for cystatin C). 5 The precision of the reference method used to measure GFR is also of high importance. The plasma iohexol clearance used by Schwartz et al is precise and reproducible in children.…”