Bachmann, Lorin M

Abstract Background Urine albumin is a key laboratory test used for classification, assessment of risk, and monitoring treatment of patients with chronic kidney disease. Urine albumin measurement results are not standardized among different measurement procedures. Consequently, clinical guidelines using fixed decision values for urine albumin cannot be applied consistently. Content Isotope dilution mass spectrometry reference measurement procedures and certified reference materials are being developed to enable standardization of immunoassay measurement procedures for urine albumin. A previous report determined calibration bias was the major error source for differences in results among different measurement procedures for urine albumin. Performance goals for between-day precision, ≤6% CV above 15 mg/L, and for specimen-specific effects, ≤6% CV, were established on the basis of the performance capability of current measurement procedures. The biological variation model was used to estimate a total allowable error of ≤24%–30% and from that the goal for bias of ≤7%–13%. Summary A reference system of higher-order certified reference materials and reference measurement procedures is being developed to enable standardization of urine albumin measurement results. Goals have been established for total allowable error, specimen-specific effects, imprecision, and bias to facilitate efforts to standardize urine albumin measurement results.

Abstract BACKGROUND Urine albumin is the primary biomarker for detection and monitoring of kidney damage. Because fixed decision criteria are used to identify patients with increased values, we investigated if commonly used routine measurement procedures gave comparable results. METHODS Results from 17 commercially available urine albumin measurement procedures were investigated vs an isotope dilution mass spectrometry (IDMS) procedure. Nonfrozen aliquots of freshly collected urine from 332 patients with chronic kidney disease, diabetes, cardiovascular disease, and hypertension were distributed to manufacturers to perform urine albumin measurements according to the respective instructions for use for each procedure. Frozen aliquots were used for measurements by the IDMS procedure. An error model was used to determine imprecision and bias components. RESULTS Median differences between the largest positive and negative biases vs IDMS were 45%, 37%, and 42% in the concentration intervals of 12–30 mg/L, 31–200 mg/L, and 201–1064 mg/L, respectively. Biases varied with concentration for most procedures and exceeded ±10% over the concentration interval for 14 of 16 quantitative procedures. Mean biases ranged from −35% to 34% at 15 mg/L. Dilution of samples with high concentrations introduced bias for 4 procedures. The combined CV was >10% for 5 procedures. It was not possible to estimate total error due to dependence of bias on concentration. CVs for sample-specific influences were 0% to 15.2%. CONCLUSIONS Bias was the dominant source of disagreement among routine measurement procedures. Consequently, standardization efforts will improve agreement among results. Variation of bias with concentration needs to be addressed by manufacturers.