Background: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. Approach: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using “cystatin c” as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted “gold standards” for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. Content: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. Summary: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.

Soluble transferrin receptor (sTfR) and ferritin concentrations were measured in a variety of clinical settings to compare the ability of these two tests to identify iron deficiency. Among 62 anemic patients who either had a bone marrow aspirate performed or had a documented response to iron therapy, the diagnostic sensitivity and specificity of sTfR (at a diagnostic cutoff of >2.8 mg/L) were 92% and 84%, respectively, with a positive predictive value of 42% in this population. Ferritin (≤12 μg/L) had a sensitivity of 25% and a specificity of 98%. However, the sensitivity and specificity of ferritin could be improved to 92% and 98%, respectively, by using a diagnostic cutoff value of ≤30 μg/L, resulting in a positive predictive value of 92%. Ferritin and sTfR were also measured in 267 outpatient samples and 112 medical students. In the outpatient group, the two tests agreed in 73% of the samples; however, 25% of the samples had ferritin values >12 μg/L and increased sTfR. Among the medical students, there was 91% agreement between the two tests, but 7% of the samples had ferritin ≤12 μg/L and normal sTfR. Together, these data suggest that measurement of sTfR does not provide sufficient additional information to ferritin to warrant routine use. However, sTfR may be useful as an adjunct in the evaluation of anemic patients, whose ferritin values may be increased as the result of an acute-phase reaction.

The management reporting and assessment of glycemic control lacks standardization. The use of different methods to measure the blood glucose concentration and to report the performance of insulin treatment yields major disparities and complicates the interpretation and comparison of clinical trials. We convened a meeting of 16 experts plus invited observers from industry to discuss and where possible reach consensus on the most appropriate methods to measure and monitor blood glucose in critically ill patients and on how glycemic control should be assessed and reported. Where consensus could not be reached, recommendations on further research and data needed to reach consensus in the future were suggested. Recognizing their clear conflict of interest, industry observers played no role in developing the consensus or recommendations from the meeting. Consensus recommendations were agreed for the measurement and reporting of glycemic control in clinical trials and for the measurement of blood glucose in clinical practice. Recommendations covered the following areas: How should we measure and report glucose control when intermittent blood glucose measurements are used? What are the appropriate performance standards for intermittent blood glucose monitors in the ICU? Continuous or automated intermittent glucose monitoring - methods and technology: can we use the same measures for assessment of glucose control with continuous and intermittent monitoring? What is acceptable performance for continuous glucose monitoring systems? If implemented, these recommendations have the potential to minimize the discrepancies in the conduct and reporting of clinical trials and to improve glucose control in clinical practice. Furthermore, to be fit for use, glucose meters and continuous monitoring systems must match their performance to fit the needs of patients and clinicians in the intensive care setting.See related commentary by Soto-Rivera and Agus, http://ccforum.com/content/17/3/155

BACKGROUND For many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope–labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays. CONTENT The Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials—in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry—is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care.

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