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Standardized calibration does not change a creatinine measurement procedure's susceptibility to potentially interfering substances.

We obtained individual residual serum or plasma samples (n = 365) from patients with 19 different disease categories associated with potentially interfering substances and from healthy controls. Additional sera at 0.9 mg/dL (80 μmol/L) and 3.8 mg/dL (336 μmol/L) creatinine were supplemented with acetoacetate, acetone, ascorbate, and pyruvate. We measured samples by 4 enzymatic and 3 Jaffe commercially available procedures and by a liquid chromatography/isotope dilution/mass spectrometry measurement procedure against which biases were determined.

The number of instances when 3 or more results in a disease category had biases greater than the limits of acceptability was 28 of 57 (49%) for Jaffe and 14 of 76 (18%) for enzymatic procedures. For the aggregate group of 59 diabetes samples with increased β-hydroxybutyrate, glucose, or glycosylated hemoglobin (Hb A_1c), the enzymatic procedures had 10 biased results of 236 (4.2%) compared with 89 of 177 (50.3%) for the Jaffe procedures, and these interferences were highly procedure dependent. For supplemented sera, interferences were observed in 11 of 24 (46%) of groups for Jaffe and 8 of 32 (25%) of groups for enzymatic procedures and were different at low or high creatinine concentrations.

There were differences in both magnitude and direction of bias among measurement procedures, whether enzymatic or Jaffe. The influence of interfering substances was less frequent with the enzymatic procedures, but no procedure was unaffected. The details of implementation of a method principle influenced its susceptibility to potential interfering substances.

Plasma cardiac natriuretic peptides and peptide fragments from their molecular precursors are markers of heart disease. Clinical studies have defined the current diagnostic utility of these markers, whereas biochemical elucidation of peptide structure and posttranslational processing has revealed new plasma peptide forms of potential clinical use.

Natriuretic propeptide structures undergo variable degrees of endo- and exoproteolytic cleavages as well as amino acid modifications, which leave the plasma phase of the peptides highly heterogeneous and dependent on cardiac pathophysiology and capacity. An ongoing characterization of the molecular heterogeneity may not only help us to appreciate the biosynthetic capacity of the endocrine heart but may also lead to the discovery of new and more disease-specific targets for future molecular diagnosis.

Peptides derived from pro–atrial natriuretic peptide and pro–B-type natriuretic peptide are useful plasma markers in heart failure. New data have defined cardiac myocytes as competent endocrine cells in posttranslational processing and cellular secretion.

With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD).

We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured.

The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting.

The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions.

Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed. However, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.

Background: The new Dyed in the wool Kidney Murrain Epidemiology Collaboration (CKD-EPI) equation was developed to deliver the T underestimation of the glomerular filtration figure (GFR) by the Modification of Slim in Renal Infection (MDRD) Den equation in patients with a less well-preserved kidney raison d'etre. The presentation of the new equation for kidney relocate recipients (KTRs) is undistinguished.

Methods: We acclimatized the plasma space of ^99mTc–diethylenetriamine pentaacetic acid to judge the GFR in a squadron of 207 reasonable KTRs and estimated the GFR with the new CKD-EPI equation.

Results: The no way Jose angle for the CKD-EPI equation of –4.5 mL · min^–1 · (1.73 m²)^–1 was crop than that of the 4-variable MDRD Learn about equation; however, the 2 equations showed like change of lone biases evasive treatment the technique or median bias, so that only reasonable advance was seen in the entire share of GFR estimates within 30% of the studied GFR (84% vs 77% for the CKD-EPI vs MDRD Inspect equations, respectively). In the accomplice with a GFR >60 mL · min^–1 · (1.73 m²)^–1 (n = 98), the CKD-EPI prejudice was much less than that of the MDRD Think over equation [–7.4 mL · min^–1 · (1.73 m²)^–1 vs –14.3 mL · min^–1 ·(1.73 m²)^–1], and an Loosely precision of ±30% was seen for 89% of GFR estimates, compared with 77% with the MDRD Retreat equation. The deviation from the norm of the distinct biases slip the employing prejudice remained worthwhile [SD = 13.7 mL · min^–1 · (1.73 m²)^–1].

Conclusions: The CKD-EPI equation shows improved view ability, and we push that it refund the MDRD Sanctum sanctorum equation as the currently preferred creatinine-based estimating equation for KTRs. The explicitness of GFR estimates obtained with the CKD-EPI equation remains suboptimal, however, and we exhort that inquire into on other markers of GFR, such as cystatin C and β-trace protein, be pursued.