Tae-Dong Jeong

Relationship between Serum Total Cholesterol Level and Serum Biochemical Bone Turnover Markers in Healthy Pre- and Postmenopausal Women

Background. The presence of common risk factors suggests that there is a relationship between osteoporosis and cardiovascular disease, possibly via dyslipidemia and inflammation. We investigated the relationships among the lipid profile, the inflammation marker high-sensitivity C-reactive protein (hsCRP), bone turnover markers, and bone mineral density (BMD) to assess the correlation between osteoporosis and cardiovascular disease and identify factors predicting osteoporosis. Methods. The study included 759 Korean women older than 20 years of age. The BMD, serum lipid profile, and levels of hsCRP, cross-linked C-terminal peptide (CTX), and osteocalcin were measured. We compared the serum biomarkers between groups with normal and low BMD and assessed the correlations between the levels of bone turnover markers and the lipid profile and hsCRP level. Results. The concentrations of CTX, osteocalcin, and total cholesterol were significantly higher in the low BMD group than in the normal BMD group in premenopausal women group. However, hsCRP was not correlated with these parameters. Multivariate logistic regression analysis revealed that TC (OR, 1.647; 95% CI, 1.190–2.279) and osteocalcin (OR, 1.044; 95% CI, 1.002–1.088) had an increased risk of low BMD in premenopausal women. Conclusions. These results indicate that total cholesterol concentration is correlated with the levels of bone turnover markers, suggesting that it might predict osteoporosis in premenopausal women.

Comparison of the MDRD Study and CKD-EPI Equations for the Estimation of the Glomerular Filtration Rate in the Korean General Population: The Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010

Background: We compared the accuracy of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in Korean patients and evaluated the difference in CKD prevalence determined using the two equations in the Korean general population. Methods: The accuracy of the two equations was evaluated in 607 patients who underwent a chromium-51-ethylenediaminetetraacetic acid GFR measurement. Additionally, we compared the difference in CKD prevalence determined by the two equations among 5,822 participants in the fifth Korea National Health and Nutrition Examination Survey, 2010. Results: Among the 607 subjects, the median bias of the CKD-EPI equation was significantly lower than that of the MDRD study equation (0.9 vs. 2.2, p=0.020). The accuracy of the two equations was not significantly different in patients with mGFR <60 mL/min/1.73m2; however, the accuracy of the CKD-EPI equation was significantly higher than that of the MDRD study equation in patients with GFR ≥60 mL/min/1.73m2. The prevalences of the CKD stages 1, 2 and 3 in the Korean general population were 47.56, 49.23, and 3.07%, respectively, for the MDRD study equation; and were 68.48, 28.89, and 2.49%, respectively, for the CKD-EPI equation. Conclusions: These data suggest that the CKD-EPI equation might be more useful in clinical practice than the MDRD study equation in Koreans.

Neutrophil gelatinase-associated lipocalin as an early biomarker of acute kidney injury in liver transplantation

Acute kidney injury (AKI) is a common complication and a significant prognostic factor of long‐term outcome in patients undergoing liver transplantation. We evaluated the utility of urine and plasma neutrophil gelatinase‐associated lipocalin (NGAL) concentrations as biomarkers of AKI during and after liver transplantation.

Development and validation of the Korean version of CKD-EPI equation to estimate glomerular filtration rate.

BACKGROUND The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was derived mostly from Caucasian, African-American, and Hispanic populations, whereas Asian populations were excluded. The aim of this study was to develop and validate a Korean version of the CKD-EPI equation. METHODS The study enrolled 960 individuals 18years old and older who underwent chromium-51-ethylenediaminetetraacetic-acid-based glomerular filtration rate (GFR) measurements. They were divided randomly into two groups: a development set (n=768, 80%) and a validation set (n=192, 20%). The Korean CKD-EPI equation was developed using a non-linear mixed-effect model. The performance of the equation was evaluated by calculating the bias (estimated GFR-measured GFR). The ±10% (P10) and ±30% (P30) accuracies and root mean square errors (RMSEs) of the original and Korean CKD-EPI equations were compared. RESULTS The Korean CKD-EPI equation was as follows: male, serum creatinine (Scr) ≤80μmol/L, GFR=141×(Scr/0.9)(-0.642)×(0.993)(Age); male, Scr>80μmol/L, GFR=141×(Scr/0.9)(-1.128)×(0.993)(Age); female, Scr≤62μmol/L, GFR=144×(Scr/0.7)(-0.465)×(0.993)(Age); female, Scr>62μmol/L, GFR=144×(Scr/0.7)(-1.382)×(0.993)(Age). The mean bias (mL/min/1.73m(2)) of the original CKD-EPI equation was -3.0±13.5 and that of the Korean CKD-EPI equation -2.3±13.3. The P10 and P30 of the original CKD-EPI equation were 33.9% and 82.8%; for the Korean CKD-EPI equation, the corresponding values were 35.4% and 85.9%. The RMSEs of the original and Korean CKD-EPI equations were 13.7 and 13.5, respectively. CONCLUSIONS The overall analytical performance of the Korean CKD-EPI equation was equivalent to that of the original CKD-EPI equation. The original CKD-EPI equation is therefore also valid for the Korean population.

Role of Soluble ST2 as a Prognostic Marker in Patients with Acute Heart Failure and Renal Insufficiency

This study sought to assess the relationship between serum concentrations of the soluble ST2 (sST2) and B-type natriuretic peptide (BNP) and investigate the role of sST2 as a prognosticator in patients hospitalized with acute heart failure (HF) and renal insufficiency. sST2 was measured at admission and discharge in 66 patients hospitalized with acute decompensated HF and renal insufficiency (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2) using a high sensitivity immunoassay. BNP was sampled at the same time and compared to sST2. Demographical, biochemical, and echocardiographic data were also obtained during hospitalization.There were positive correlations between sST2 and BNP levels at admission (r = 0.330, P = 0.007) and at discharge (r = 0.320, P = 0.009) in overall patients. However, there was no correlation between them at each timepoint in patients with severe renal insufficiency (eGFR < 30 mL/min/1.73 m2, n = 17). sST2 level was not changed with the degree of renal function, even though BNP level was much higher in patients with severe renal insufficiency. During 3 month follow-up, 9 (13.6%) died and 16 (24.2%) were readmitted due to HF aggravation.On multivariate analysis, sST2 at discharge was independently associated with death or HF readmission during 3 months after discharge (hazard ratio, 1.038; 95% confidence interval, 1.011-1.066, P = 0.006). In conclusion, sST2 is not affected by renal function compared with BNP in acute HF patients. The measurement of predischarge sST2 can be helpful in predicting short-term outcomes in acute decompensated HF patients with renal insufficiency.

CYP2C19 Genotype and Early Ischemic Lesion Recurrence in Stroke Patients Treated with Clopidogrel

BACKGROUND Early recurrent ischemic lesions detected on diffusion-weighted imaging (DWI) have been proposed as a surrogate marker for clinical recurrence. We hypothesized that cytochrome P450 2C19 (CYP2C19) genotype influences the incidence of early recurrence on DWI in acute stroke patients treated with clopidogrel. METHODS We enrolled 76 Korean patients with acute ischemic stroke due to large artery atherosclerosis who were treated with clopidogrel. Early ischemic lesion recurrence was defined as new lesions separate from the index lesion. We compared the rates of early ischemic lesion recurrence on DWI based on the CYP2C19 genotypes. RESULTS Early recurrence on DWI was observed in 36 patients (47.4%). A total of 76 patients were classified into 3 phenotypic groups: extensive metabolizers (EMs; n = 27, 35.5%), intermediate metabolizers (IMs; n = 36, 47.4%), and poor metabolizers (PMs; n = 13, 17.1%). Early recurrence on DWI was more common in PMs (84.6%), followed by IMs (50.0%), and EMs (25.9%; P < .001). PMs had a significantly higher recurrence rate than EMs (P < .001). In multivariate analysis, CYP2C19 genotypes were independently associated with early DWI recurrence (for PMs: odds ratio, 19.3; 95% confidence interval, 3.15-117.56). CONCLUSIONS CYP2C19 genotypes are significantly associated with early lesion recurrence in Korean acute stroke patients treated with clopidogrel.

An efficient genomic DNA extraction from whole blood using Nextractor.

BACKGROUND We evaluated the performance of the Nextractor NX-48 nucleic acid extractor system for the extraction of genomic DNA from whole blood samples. METHODS We compared the performance of the Nextractor to that of the QIAamp DNA Blood Mini Kit and the Maxwell system, using five whole blood samples. Extraction efficiencies were compared based on the total amount of extracted DNA adjusted by input blood volume, and the purity was compared. Polymerase chain reaction analyses were performed using ACTB as a target. The real-time PCR assay was carried out for housekeeping gene GAPDH. Total elapsed time for DNA extraction was compared. RESULTS Extraction efficiencies for the QIAamp, Maxwell, and Nextractor were 25.4±3.8ng/μL, 9.2±0.6ng/μL, and 31.0±5.6ng/μL, respectively. No significant differences in purity were observed among three methods. DNA extracted using the ACTB was successfully amplified in all three methods. There were no obvious differences in Ct values for GAPDH real-time PCR. Total elapsed time for DNA extraction was about 50min for the QIAamp, 40min for the Maxwell, and 20min for the Nextractor. CONCLUSIONS As the Nextractor is faster and requires less hands-on time than manual procedures, it may be useful for molecular diagnostic testing in clinical laboratories.

A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA).

Abstract Background: Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results. Methods: HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20–1500 and 17.2–2637.8 pmol/L; Architect CA125 II assay, 1–1000 and 3.9–14,163.0 U/mL; Elecsys HE4 assay, 15–1500 and 28.8–3847 pmol/L; Elecsys CA125 II assay, 0.6–5000 and 6.5–5000 U/mL. These values were used to simulate the ROMA values. Results: Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is <20 and <28.8 for Abbott and Roche in premenopausal woman, the ROMA value should be reported as “low risk” regardless of the CA125 result. In postmenopausal woman, however, it should be reported as “low risk” (CA125<203.0 and <165.8 for Abbott and Roche) or “undetermined” (vice-versa value). (3) If CA125 value is <3.9 and <6.5 for Abbott and Roche, it should be reported as “low risk” (premenopausal HE4<51.5 and <62.2, postmenopausal HE4<323.0 and <281.5 for Abbott and Roche) or “undetermined” (vice-versa value). Conclusions: New reporting strategy will provide more informative reporting of ROMA values in clinical practice.

Comparison of red blood cell hemolysis using plasma and serum separation tubes for outpatient specimens.

Background To rapidly obtain outpatient results, we use plasma separation tubes (PST) for chemistry analysis. If lactate dehydrogenase measurement is required, serum separation tubes (SST) are used. There has been no evaluation of hemolysis with these tubes. We compared the hemolytic index (HI) obtained by using PST and SST and applied this for choosing appropriate tubes for clinical laboratories. Methods The HI of specimens obtained from outpatients visiting Asan Medical Center between July and December 2012 was analyzed. The HI was scored from 0 to 10 by using the Toshiba 200FR (Toshiba Medical Systems Co., Japan). HI was classified by sample tube type, and significant hemolysis was defined as a HI of 2 or more. For significant hemolysis cases, medical records were reviewed to identify the causes. Results Among 171,519 specimens, significant hemolysis was observed in 0.66% of specimens (0.68% of PST specimens, 0.46% of SST specimens). The mean HI in PST was 0.18 (SD: 0.43) and that in SST was 0.14 (SD: 0.37). The proportion of significant hemolysis was significantly higher in PST than in SST (P=0.001). The cause of significant hemolysis was identified as chemotherapy and prosthetic valve in 48.1% of specimens. Complex sampling errors may have caused significant hemolysis in the remaining 51.9% of specimens. Conclusions The incidence of hemolysis was slightly higher for PST than SST, although both were <1%. PST are thought to be more useful than SST in outpatient testing because of rapid turnaround time, greater sample volume, and less risk of random errors due to fibrin strands.

Statistical validation of reagent lot change in the clinical chemistry laboratory can confer insights on good clinical laboratory practice

Verification of new lot reagent’s suitability is necessary to ensure that results for patients’ samples are consistent before and after reagent lot changes. A typical procedure is to measure results of some patients’ samples along with quality control (QC) materials. In this study, the results of patients’ samples and QC materials in reagent lot changes were analysed. In addition, the opinion regarding QC target range adjustment along with reagent lot changes was proposed. Patients’ sample and QC material results of 360 reagent lot change events involving 61 analytes and eight instrument platforms were analysed. The between-lot differences for the patients’ samples (ΔP) and the QC materials (ΔQC) were tested by Mann–Whitney U tests. The size of the between-lot differences in the QC data was calculated as multiples of standard deviation (SD). The ΔP and ΔQC values only differed significantly in 7.8% of the reagent lot change events. This frequency was not affected by the assay principle or the QC material source. One SD was proposed for the cutoff for maintaining pre-existing target range after reagent lot change. While non-commutable QC material results were infrequent in the present study, our data confirmed that QC materials have limited usefulness when assessing new reagent lots. Also a 1 SD standard for establishing a new QC target range after reagent lot change event was proposed.