A limitation of proteomic methods with respect to their clinical applicability is the lack of possibilities to directly deduce the amount of a protein or peptide from a particular mass spectrometry (MS) spectrum. For quantification of chronic kidney disease (CKD)-specific urinary polypeptides in capillary electrophoresis coupled with mass spectrometry (CE-MS), we compared signal intensity calibration methods based on either urinary creatinine or stable isotope labeled synthetic marker analogues (absolute quantification) with those based on ion counting using highly abundant collagen fragments as nonmarker references (relative quantification). Our results indicate that relative quantification of biomarker excretion based on ion counts in reference to endogenous "housekeeping" peptides is sufficient for the determination of urinary polypeptide levels. The calculation of absolute concentrations via exogenous stable isotope-labeled peptide standards is of no additional benefit.
Cystatin C, a low molecular weight protein, is a new endogenous marker of renal function whose serum concentration correlates better with glomerular filtration rate than creatinine. The aim of the present study was to define a reference interval for cystatin C concentrations in children. Cystatin C was measured by an immunoturbidimetric assay in sera obtained from 258 children (93 girls, 165 boys, median age 6.29 years, range 1 day to 18 years) without evidence of kidney disease. The reference interval was calculated non-parametrically using the 2.5th and 97.5th percentiles. For comparison, creatinine was measured in the same samples. The cystatin C concentration was highest on the first days of life (range 1.64-2.59 mg/l) with a rapid decrease during the first 4 months. Beyond the 1st year, the cystatin C concentration was constant, with a reference interval of 0.7-1.38 mg/l. In contrast, serum creatinine concentrations steadily increased with age until adulthood. Compared with creatinine, cystatin C facilitates the recognition of abnormal renal function in children as its reference range is constant beyond the 1st year of life. The higher levels of cystatin C in the 1st year of life probably reflect the low glomerular filtration rate of neonates and infants.
This paper is the fourth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 2.
This paper is the fifth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 3.
This paper is the ninth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C and the certification of reference preparations. Other parts deal with: Part 1. The concept of reference procedures for the measurement of catalytic activity concentrations of enzymes; Part 2. Reference procedure for the measurement of catalytic concentration of creatine kinase; Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase; Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase; Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase; Part 6. Reference procedure for the measurement of catalytic concentration of γ-glutamyltransferase; Part 7. Certification of four reference materials for the determination of enzymatic activity of γ-glutamyltransferase, lactate dehydrogenase, alanine aminotransferase and creatine kinase at 37 °C; Part 8. Reference procedure for the measurement of catalytic concentration of α-amylase. The procedure described here is derived from the previously described 30 °C IFCC reference method. Differences are tabulated and commented on in Appendix 1.
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