Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function.

BACKGROUND: To determine the potential sensitivity of several renal function tests for detecting early changes in renal function, we compared the within-individual (W-I) variation over 5 months of serum creatinine, serum cystatin C, and creatinine clearance. METHODS: On 31 healthy subjects, blood and timed urine specimens were collected once each month to get 6 collections. Creatinine (enzymatic) in serum and urine and cystatin C (immunonephelometric) in serum were measured and glomerular filtration rate (GFR) by creatinine clearance and the Modification of Diet in Renal Disease (MDRD) equation were calculated. To compare W-I variations between different creatinine methods, we also measured creatinine by both enzymatic and kinetic alkaline picrate methods on 15 sets of frozen samples. RESULTS: For the 31 volunteers, the mean W-I variations for serum creatinine (5.8%) and cystatin C (5.4%) were both much lower than the W-I variation of creatinine clearance (18.7%). As expected, the MDRD GFR had a similar W-I variation (6.7%) to that of serum creatinine and its values were markedly different than GFR by creatinine clearance. On the 15 sets of frozen samples, the W-I variation of creatinine measured by the enzymatic method (CV 5.2%) was slightly less than by the picrate method (CV 6.2%). CONCLUSIONS: The low W-I variation of both serum cystatin C and serum creatinine suggests that serial measurements of either would detect a changes in renal function earlier than would GFR by creatinine clearance or MDRD equation, which allows reporting only for GFRs<60 ml/min/1.7 m(2). While we measured only creatinine clearance, the large variability, difficulty, and cost of all clearance measurements make them impractical for routine monitoring of patients.

Validation of a quality assessment system for blood gas and electrolyte testing.

BACKGROUND: A recently-introduced quality assessment system (Intelligent Quality Management: iQM), was evaluated in routine clinical use at four different hospitals. The iQM technology is designed to replace conventional external liquid controls with software, Process Control (PC) Solutions and Calibration Validation components that continually assess the function of the GEM Premier 3000 (GEM) analyzer and automatically initiate and document corrective actions. METHODS: We validated the performance claims of iQM by monitoring quality control (QC) materials at 4 clinical sites while analyzing approximately 10,550 patient samples. We compared iQM-measured QC values to traditional QC results, evaluating the number and type of error flags for patient samples, and used data from control results to calculate the average time to detect an error (ADT) for each analyte. RESULTS: The calculated ADT was approximately 3 min for all analytes except for sodium (17 min), glucose (11 min), and lactate (5.9 min). Precision of control materials in iQM cartridges was better than from external controls run on traditional analyzers. The iQM system detected errors in 0.46% of actual clinical samples. CONCLUSIONS: The findings from our study confirm that (a) iQM precision in a clinical setting is comparable to that found in previous studies done in a research setting, (b) the improved precision of control material on the iQM is likely because the internal control fluids are sealed and not susceptible to exposure from handling, and (c) the system detects and often corrects errors in specific samples that might not be reported by traditional analytical systems.

pH effects on measurements of ionized calcium and ionized magnesium in blood.

CONTEXT: It is well known that the concentration of ionized calcium in blood is affected by the pH of the specimen, since hydrogen ions compete with calcium for binding sites on albumin and other proteins. However, the relationship between pH and ionized magnesium concentration is not as well characterized. OBJECTIVE: To determine the effects of pH on ionized magnesium concentration over a wide range of pH values in serum or plasma. DESIGN: Both ionized calcium and ionized magnesium concentrations were measured in 3 sets of samples. (1) Pools of serum or whole blood at different pH values (7.20-7.60) achieved by adding a constant volume of acid or base (diluted solutions of either hydrochloric acid or sodium hydroxide) plus saline. These pools consisted of 2 serum and 3 heparinized whole blood pools collected from leftover blood remaining in clinical specimens in the Clinical Chemistry and Blood Gas Laboratories, respectively, at Duke University Medical Center. (2) Five whole blood specimens obtained from apparently healthy individual donors. (3) Twenty-six whole blood specimens obtained from individual patients (leftover blood from the Blood Gas Laboratory) in which pH was varied by in vitro loss or gain of carbon dioxide. RESULTS: Both ionized calcium and ionized magnesium concentrations decreased as the pH in the specimen increased, indicating the stronger binding of these ions with proteins in the more alkaline environment. CONCLUSION: We conclude that the rate of change of ionized magnesium concentration with pH change (0.12 mmol/L per pH unit) is significantly less than that of ionized calcium (0.36 mmol/L per pH unit). Furthermore, our findings indicate that if adjustment to pH 7.40 is necessary, the ionized magnesium test results need to be adjusted when pH is markedly abnormal, as is sometimes done for ionized calcium.