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Title Standardisation of Creatinine Whole Blood Measurement Method
Author Hansen, Lea Bugge
Jensen, Signe Wej
Supervisor Andersen, Klaus Kaae (Mathematical Statistics, Department of Informatics and Mathematical Modeling, Technical University of Denmark, DTU, DK-2800 Kgs. Lyngby, Denmark)
Spliid, Henrik (Mathematical Statistics, Department of Informatics and Mathematical Modeling, Technical University of Denmark, DTU, DK-2800 Kgs. Lyngby, Denmark)
Institution Technical University of Denmark, DTU, DK-2800 Kgs. Lyngby, Denmark
Thesis level Master's thesis
Year 2008
Abstract The motive for this thesis is a recommendation from the National Kidney Disease Education Program (NKDEP). They encourage all manufacturers of creatinine measurement devices to standardise their measurement methods to yield measurements that are traceable to high-level isotope dilution mass spectrometry (IDMS) [42]. The intention with the standardisation is to reduce the interlaboratory variation in creatinine estimation and enable more accurate estimates of glomerular filtration rate (GFR). GFR is today widely used to diagnose chronic kidney disease (CKD), a disease that implies a progressive loss of renal function. Today, the incidence in Europe of end-stage renal disease, the final stage of CKD, is around 135 per million inhabitants per year [23], a number that is expected to increase over the next decades, primarily as a consequence of the global epidemic of type 2 diabetes and the ageing of the population in developed countries. An improved accuracy of GFR estimates will enable physicians to detect CKD sooner and allow for treatment at an earlier stage, which can slow down the progression of the disease markedly. This thesis deals with the standardisation of a RadiometerMedical ApS (RMED) creatinine whole blood measurement method according to a guideline developed by NKDEP for whole blood measurements specifically. A calibration correction was established from tests performed on whole blood samples and simultaneously collected plasma samples. As a hematocrit dependence was observed in the measurements, hematocrit was included as a variable in the correction equation. A verification test showed that calibration of creatinine whole blood measurements using the obtained correction improves the performance of the measurement method from being unacceptable (based on the 6σ methodology) to being in the 4σ-5σ range, except for creatinine concentrations around 70 μmol/L, where a high reproducibility leads to an unacceptable performance. NKDEP has also specified performance goals for the creatinine measurement method and they deviate a little from the 6σ performance classification. When using the NKDEP performance goals to evaluate the measurement performance, it is classified between optimum and desirable after standardisation (again except for creatinine concentrations around 70 μmol/L), while it was between desirable and minimum prior to the standardisation. From the verification test it can be concluded that standardisation of creatinine whole blood measurements using the established hematocrit dependent calibration correction yields a reduction in total error (TE) and thus an improved performance of the measurement method, particularly in the creatinine range 70 μmol/L to 350 μmol/L and the hematocrit range 30% to 45%. This is considered very satisfactory as the mentioned creatinine range is the clinically relevant range when diagnosing early-stage CKD, and the hematocrit range is the range that covers the vast majority of patients.
Series IMM-M.Sc.-2008-82
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Admin Creation date: 2008-09-01    Update date: 2008-09-01    Source: dtu    ID: 222769    Original MXD