Xiuzhi Guo

Improved glomerular filtration rate estimation using New equations combined with standardized cystatin C and creatinine in Chinese adult chronic kidney disease patients

OBJECTIVES The newly developed glomerular filtration rate (GFR)-estimating equations developed by the CKD-EPI Collaboration and Feng et al. (2013) that are based on standardized serum cystatin C (ScysC), combined/not combined with serum creatinine (Scr), require further validation in China. We compared the performance of four new equations (CKD-EPIcys, CKD-EPIcr-cys, Fengcys, and Fengcr-cys equations) with the CKD-EPI creatinine equation (CKD-EPIcr) in adult Chinese chronic kidney disease (CKD) patients to clarify their clinical application. DESIGN AND METHODS GFR was measured using the dual plasma sampling (99m)Tc-DTPA method (mGFR) in 252 adult CKD patients enrolled from four centres. Scr and ScysC were measured by standardized assays in a central laboratory. Each equations performance was assessed using bias, precision, accuracy, agreement, and correct classification of the CKD stage. RESULTS The measured GFR was 46 [25-83] mL/min per 1.73 m(2). The CKD-EPIcys, CKD-EPIcr-cys and Fengcys equations provided significantly higher accuracy (P15: 38.9%, 39.7%, and 38.9%) than the CKD-EPIcr equation (29.8%). The CKD-EPIcr-cys and Fengcr-cys equations presented higher precision (IQR of the difference, 16.4 and 17.3 mL/min per 1.73 m(2), respectively) and narrower acceptable limits in Bland-Altman analysis (56.6 and 50.8 mL/min per 1.73 m(2), respectively) than single marker-based equations. The CKD-EPIcr-cys equation achieved the highest overall correct proportion (61.5%) in classification of CKD stages. CONCLUSIONS Combining ScysC and Scr measurements for GFR estimation improves diagnostic performance. The Scr-ScysC equation showed better performance than equations based on either marker alone. The CKD-EPIcr-cys equation showed the best performance for GFR estimation in Chinese adult CKD patients.

High prevalence of coexisting prehypertension and prediabetes among healthy adults in northern and northeastern China

BackgroundPrehypertension and prediabetes are major risk factors of cardiovascular disease, and their combined presence may result in more serious cardiovascular outcomes than expected with either prehypertension or prediabetes alone. The aim of the present study was to evaluate the prevalence of coexisting prehypertension and prediabetes, and the associated risk profiles in a Chinese population.MethodsA cross-sectional survey in a representative sample of 3,595 men and 4,593 women aged 18 years and older was performed between 2008 and 2010. Prehypertension and prediabetes were diagnosed using the guidelines from the Seventh Report of the Joint National Committee on prevention, detection, and treatment of high blood pressure and American Diabetes Association, respectively. Prehypertension was defined as a systolic blood pressure of 120-139 mmHg and/or diastolic blood pressure of 80-89 mmHg, and prediabetes was defined as a fasting blood glucose of 5.6-6.9 mmol/L.ResultsThe prevalence of coexisting prehypertension and prediabetes was 11.0%. Men had a higher prevalence of coexisting prehypertension and prediabetes than women (14.2% vs. 8.4%; P < 0.0001). This prevalence increased with age and body mass index, and was the lowest among Mongolian-Chinese (5.1%). A multivariate analysis showed that γ-glutamyltransferase and uric acid were significantly and positively correlated with body mass index, waist circumference, blood pressure, triglycerides, and total cholesterol, and negatively correlated with high density lipoprotein cholesterol in subjects with prehypertension and prediabetes.ConclusionsThere is a large proportion of Chinese adults with coexisting prehypertension and prediabetes. Thus, there is a need for more efforts that implement public health programs that target the earlier stages of hypertension and diabetes.

Hyperuricemia and clustering of cardiovascular risk factors in the Chinese adult population

Hyperuricemia is common in China and the relevance of hyperuricemia and cardiovascular disease (CVD) risk has been highlighted, but to date there has been rarely nation-wide study in China. Here, we aim to estimate the current prevalence of hyperuricemia and evaluate the associations between hyperuricemia and cardiovascular risk factors (CRFs) clustering in a large sample of China adults including a plurality of ethnic minorities. Generally, a nationally representative sample of 22983 adults aged ≥18 years was recruited from 2007 to 2011. Questionnaire data and information on anthropometric characteristics, and laboratory measurements were collected. We define hyperuricemia as SUA ≥416 mmol/L for men and SUA ≥357 mmol/L for women. We found that the prevalence of hyperuricemia was 13.0% (18.5% in men and 8.0% in women). To our estimation, hyperuricemic subjects had higher prevalence rates of CRFs clustering than non-hyperuricemic subjects. Furthermore, there was a dose-response association between the number of CVD risk factors clustering and hyperuricemia. Our study revealed a high prevalence of hyperuricemia and CVD risk factors clustering among Chinese adults, and hyperuricemia was significantly associated with coexistence of more CVD risk factors. Therefore, guidance and effective lifestyle intervention are required to prevent hyperuricemia and CVD risk factors in China.

Strong Negative Interference by Calcium Dobesilate in Sarcosine Oxidase Assays for Serum Creatinine Involving the Trinder Reaction

Abstract The vasoprotective drug calcium dobesilate is known to interfere with creatinine (Cr) quantifications in sarcosine oxidase enzymatic (SOE) assays. The aim of this study was to investigate this interference in 8 different commercially available assays and to determine its clinical significance. In in vitro experiments, interference was evaluated at 3 Cr levels. For this, Cr was quantified by SOE assays in pooled serum supplemented with calcium dobesilate at final concentrations of 0, 2, 4, 8, 16, 32, and 64 &mgr;g/mL. Percent bias was calculated relative to the drug-free specimen. For in vivo analyses, changes in serum concentrations of Cr, cystatin C (CysC; a renal function marker), and calcium dobesilate were monitored in healthy participants of group I before and after oral calcium dobesilate administration. In addition, variations in interference were also examined among different SOE assays using serum obtained from healthy participants of group II. Lastly, Cr levels from the 10 patients treated with calcium dobesilate were measured using 4 SOE assays and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) for comparison. Our in vitro analyses indicated that the presence of 8 &mgr;g/mL calcium dobesilate resulted in a −4.4% to −36.3% reduction in Cr serum concentration compared to drug-free serum for 8 SOE assays examined. In vivo, Cr values decreased relative to the baseline level with increasing drug concentration, with the lowest Cr levels obtained at 2 or 3 hours after drug administration in participants of group I. The observed Cr concentrations for participants in group II were reduced by −28.5% to −3.1% and −60.5% to −11.6% at 0 and 2 hours after administration related to baseline levels. The Cr values of 10 patients measured by Roche, Beckman, Maker, and Merit Choice SOE assays showed an average deviation of −20.0%, −22.4%, −14.2%, and −29.6%, respectively, compared to values obtained by LC-IDMS/MS. These results revealed a clinically significant negative interference with calcium dobesilate in all sarcosine oxidase-based Cr assays, but the degree of interference varied greatly among the assays examined. Thus, extra care should be taken in evaluating Cr quantification obtained by SOE assays in patients undergoing calcium dobesilate therapy.

Apolipoprotein E gene polymorphisms are associated with primary hyperuricemia in a Chinese population.

Objective Primary hyperuricemia, an excess of uric acid in the blood, is a major public health problem. In addition to the morbidity that is attributable to gout, hyperuricemia is also associated with metabolic syndrome, hypertension, and cardiovascular disease. This study aims to assess the genetic associations between Apolipoprotein E (APOE) polymorphisms and hyperuricemia in a Chinese population. Methods A total of 770 subjects (356 hyperuricemic cases and 414 normouricemic controls) were recruited from the Ningxia Hui Autonomous Region, China. A physical examination was performed and fasting blood was collected for biochemical tests, including determination of the levels of serum lipid, creatinine, and uric acid. Multi-ARMS PCR was applied to determine the APOE genotypes, followed by an investigation of the distribution of APOE genotypes and alleles frequencies in the controls and cases. Results The frequencies of the APOE-ε2ε3 genotype (17.70% vs. 10.39%, P = 0.003) and the APOE-ε2 allele (10.53% vs. 5.80%, P = 0.001) were significantly higher in the hyperuricemic group than in the normouricemic group. Furthermore, male cases were more likely to have the APOE-ε2ε3 genotype and APOE-ε2 allele, compared with male controls. In both Han and Hui subjects, cases were more likely to have the APOE-ε2ε3 genotype and the APOE-ε2 allele compared with controls. Furthermore, multivariate logistic regression showed that carriers of the APOE-ε2ε3 genotype (P = 0.001, OR = 2.194) and the ε2 allele (P = 0.001, OR = 2.099) were significantly more likely to experience hyperuricemia than carriers of the ε3/ε3 genotype and the ε3 allele after adjustment for sex, body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), creatinine (Cr) and fasting blood glucose(FBG). Conclusions The APOE-ε2ε3 genotype and the APOE-ε2 allele are associated with serum uric acid levels in Chinese subjects, indicating that individuals carrying the APOE-ε2 allele have a higher risk of hyperuricemia than non-carriers.

Negative interferences by calcium dobesilate in the detection of five serum analytes involving Trinder reaction-based assays

Previously, we reported the strong negative interference of calcium dobesilate, a vasoprotective agent, in creatinine assays involving the Trinder reaction. It is hypothesized that a similar effect occurs in the detection of uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). The interferences of calcium dobesilate during the detection of the five serum analytes were investigated on automated systems/analysers, and the effects were compared among eight different assay systems for each analyte. A calcium dobesilate standard was added into two sets of the blank serum pools of each analyte at final concentrations of 0, 2, 4, 8, 16, 32, and 64 μg/mL. The percentage deviation of each analyte value was calculated between each drug concentration and the drug-free samples. The clinically acceptable error levels for UA, TC, TG, HDL-C, and LDL-C were defined as ±4.87%, ±4.1%, ±9.57%, ±5.61%, and ±5.46%, respectively. The observed interference was concentration dependent for each analyte. In the presence of 16 μg/mL calcium dobesilate, which was within the therapeutic range, all seven Trinder reaction-based UA assay systems, two TG assay systems, two HDL-C assay systems and one TC assay system exhibited negative drug interferences. Calcium dobesilate negatively interferes with the detection of UA, TG, TC, and HDL-C in assay systems based on the Trinder reaction. The effect was most significant in UA and TG detection.

Methylation of NBPF1 as a novel marker for the detection of plasma cell-free DNA of breast cancer patients

BACKGROUND Recent studies revealed that tumor-specific gene methylation can be detected in the circulating cell-free DNA (cfDNA) of cancer patients; therefore, methylated cfDNA is considered a promising biomarker. Human neuroblastoma breakpoint family member 1 (NBPF1) was originally identified in a neuroblastoma (NB) patient. The present study is the first to evaluate the presence of NBPF1 gene methylation in cfDNA in plasma of breast cancer patients. METHODS Differentially methylated cfDNA was screened using bisulfite sequencing with a next-generation sequencer (BS-seq) among 25 breast cancer patients, 25 patients with a benign breast disease and 25 healthy female volunteers. Then, five specific methylation sites in the NBPF1 gene were verified in 11 breast cancer samples, and two further sites in the NBPF1 promoter were detected in 52 breast cancer patients (stages I-III), 31 patients with benign breast disease and 30 healthy controls by using methylation-specific PCR (MSP). Furthermore, the association between the methylation statuses of NBPF1 and the clinicopathological characteristics of breast cancer patients was analyzed. RESULTS BS-seq demonstrated that the NBPF1 methylation levels in breast cancer patients were higher than those in patients with benign breast disease and healthy controls. The MSP results showed that the methylation rates of two sites in the NBPF1 promoter were 67.1% and 61.4% in breast cancer patients, 48.2% and 59.6% in patients with benign breast disease, and 40.9% and 48.1% in healthy controls, respectively. The methylation rates of one site were significantly different among the three groups (p < .05), with the highest rate in breast cancer patients. Moreover, there was no statistically significant correlation between the NBPF1 promoter methylation and the major clinicopathological features of the patients. CONCLUSIONS These results indicate that hypermethylation of the NBPF1 promoter occurs in a significant proportion of breast tumors and that NBPF1-methylated cfDNA may serve as a potential tumor marker for breast cancer.

Measuring lipoprotein-associated phospholipase A2 activity in China: Protocol comparison and recalibration

Lp‐PLA2 is a novel inflammation marker in cardiovascular disease. While several manufactures have registered Lp‐PLA2 activity reagents, few studies have investigated the consistency among these assays. In this study, we compared and recalibrated Lp‐PLA2 activity assays.

Calcium dobesilate: A drug treatment for diabetic retinopathy can negatively interfere with the measurement of glycated albumin using the enzymatic method

BACKGROUND We reported that calcium dobesilate, a vasoprotective agent mainly used for diabetic retinopathy (DR), negatively interferes with glycated albumin (GA) assays involving enzymatic methods. METHODS A calcium dobesilate standard was added to 3serum pools in vitro to prepare concentration-response series according to Clinical and Laboratory Standards Institute EP7-A2 guidelines. Percentage deviation between each drug concentration and the drug-free sample was calculated for 6 commercially available GA assays. The acceptable limit of deviation for GA was ±5.61%. For in vivo analyses, changes in serum concentrations of GA and calcium dobesilate were monitored in eight healthy participants before and after oral calcium dobesilate administration. RESULTS At 16 μg/ml calcium dobesilate, within the therapeutic range, the percentage deviations for Asahi Kasei, Maccura, Leadman, Homa, and Medicalsystem assays were -8.7% to -49.7%, -2.0% to -47.7%, and -10.1% to -35.7% for low-, medium- and high-GA level interference pools, respectively, exhibiting dose-dependent negative interference. In vivo, calcium dobesilate ingestion was associated with statistically significant, falsely decreased measurements in 5 GA assays, 2 h after daily 500 mg administration. CONCLUSIONS Calcium dobesilate ingestion was associated with erroneously low measurements in 5 GA assays. The degree of interference varied greatly among the assays examined.

Effects of sex, age, sampling time, and season on thyroid-stimulating hormone concentrations: A retrospective study

BACKGROUND Measuring thyroid-stimulating hormone (TSH) is essential for diagnosing and monitoring thyroid diseases. The aim of this study was to evaluate the effect of sex, age, sampling time and season on TSH in a large Chinese population and to determine which factor had the greatest impact on TSH measurement results. METHODS Data were obtained from the laboratory information system from September 1, 2013 to August 31, 2016. A total of 80150 TSH measurements of outpatients were enrolled in this study. TSH was measured using a Siemens ADVIA Centaur XP automatic chemiluminescence immunoassay analyzer. Linear regression models were used to assess the association between log-transformed TSH concentrations and sex, age, sampling time and season. RESULTS The serum TSH concentrations in women were significantly higher than in men. In all subjects, serum TSH concentrations increased by 0.005 μIU/mL for each year of age. TSH concentrations showed circannual variation during the 3 consecutive years of data collection and decreased during the summer while increased during the winter. The serum TSH concentrations decreased from 7 a.m. to 1 p.m. while increased from 1 p.m. to 4 p.m. The same trend was observed in TSH concentrations for sampling time stratified by sex. Linear regression revealed that sampling time might be the major factor affecting serum TSH concentrations. CONCLUSION Sex, age, season, and sampling time significantly affected serum TSH concentrations. Age-related alteration in serum TSH concentrations was observed in this study. Sampling time was the major factor affecting serum TSH concentrations.