Individual Biochemical Markers Research Articles

Vitamin D status and calcium-phosphoric metabolism in children with excessive body weight and obesity

Obesity is a multifactorial disease, the prevalence of which has increased over the past few decades worldwide in all age groups. There is evidence of the pathogenetic role of vitamin D (VD) in the formation of obesity. However, there are few studies concerning the characteristics of calcium-phosphorus metabolism in obese children. Therefore, data on the prevalence of VD deficiency stratified by body mass index categories, characteristics of calcium-phosphorus homeostasis and the relationship between the concentration of parathyroid hormone (PTH) and 25(OH)D in obese children are of scientific and practical interest. The aim of the study was to assess the VD status of children, to analyze the ratio of individual biochemical markers of bone metabolism [concentration of calcium (Ca), phosphorus (P), PTH, alkaline phosphatase (ALP) activity] depending on body mass index (BMI). Material and methods. The cross-sectional (one-stage) study included 77 children with different weight and height parameters at the age from 8 to 10 years. All children were divided into 3 groups: 1st - 26 children with normal body weight, 2nd - 29 children with overweight, 3rd - 22 people with obesity. All children underwent determination of the level of 25(OH)D, PTH, alkaline phosphatase, Ca, P in blood serum. Results. Reduced VD supply occurred in all groups. However, children with normal BMI had a higher concentration of 25(OH)D - 32.65 [15.96; 44.4] ng/ml vs 23.6 [11.3; 34.54] ng/ml (p=0.001) in children with overweight and 12.51 [5.7; 19.1] ng/ml (p=0.014) in children with obesity (p<0.05). With an increase in BMI, a decrease in 25(OH)D level was noted (r=-0.480, p<0.05). Vitamin D deficiency in obese children (86.4%) occurred 2.3 fold more often than in overweight children (p=0.002), and 2.8 fold more often than in children with normal body weight (p=0.001). The concentration of PTH in all children was within the physiological norm, while there was a moderate negative correlation between the levels of PTH and 25(OH)D (r=-0.44, p<0.05). A moderate inverse correlation was also found between the concentration of PTH and total Ca (r=-0.38, p<0.05) and P (r=-0.44, p<0.05). With an increase in the BMI/age Z-score, a decrease in serum Ca level was observed (r=-0.497, p<0.05). The P content and ALP activity in blood serum were within the physiological norm in all children, however, in children with overweight and obesity, these indicators were statistically significantly lower than in healthy peers (p<0.05). Conclusion. In children with overweight and obesity, vitamin D deficit and insufficiency are recorded statistically significantly more often than in healthy children. With an increase in BMI, there is a tendency to a decrease in Ca, P and ALP.

Features of arterial hypertension in postmenopausal women with abdominal obesity: The role of inflammatory response markers, leptin, and female sex hormones in the pathogenesis of vascular wall stiffness

Background. Despite overall efforts, arterial hypertension remains one of the most significant medical and social problems. The risk of developing arterial hypertension is tripled in obese individuals compared with people who have normal body weight. According to clinical studies, individual biochemical markers can be predictors of initiation of remodeling processes in systems at a preclinical level. Endothelial dysfunction is the initial stage in the development of atherosclerosis. Mechanisms of the vascular inflammatory response in arterial hypertension with obesity can be considered a factor that largely determines the onset and course of the disease, a cause of its aggravation, development, and progression. Cardiovascular risk factors, genetic predisposition, deficit of sex hormones, and aging affect the endothelium function.Aim. To study specifics of hypertension in postmenopausal women with abdominal obesity and to evaluate the role of inflammatory response markers, leptin, and female sex hormones in the pathogenesis of vascular wall stiffness.Material and Methods. The study included 164 patients divided into three groups. Group 1 consisted of 42 healthy women aged 44.43 ± 14.26 years; group 2 comprised 62 hypertensive women aged 60.69 ± 7.09 years; group 3 comprised 60 hypertensive women with abdominal obesity aged 57.24 ± 7.40 years. Patients of all groups received 24-hour blood pressure monitoring, sphygmography, and assessment of sex hormones, lipids, inflammatory, and biochemical parameters in blood serum.Results. Results of analysis showed that patients of group 3 had significantly higher blood pressure compared with that in group 2. Higher pulse wave velocity was observed in women of group 2. Groups 2 and 3 had lower levels of sex hormones and significant increases in the levels of inflammatory markers compared with those in control group. Multiple multidirectional correlations between the studied parameters were revealed.Conclusions. Features of hypertension in postmenopausal women with obesity consist in a systolic-diastolic variant of hypertension, an increase in systolic blood pressure variability at night, an increase in diastolic blood pressure during the daytime, and increases in systolic and diastolic blood pressure at night. The method of logistic regression allowed to identify biochemical markers that determine the elastic properties of the vascular wall in this category of patients, namely: leptin, highsensitivity C-reactive protein, and endothelin-1.

Characteristics of Somatic Status and Individual Biochemical Markers in Patients with Retinal Vein Occlusion

Retinal vein occlusion is one of the most severe vascular lesions of the organ of vision, usually accompanied by somatic pathology.The aim of the study was to study the somatic status and individual biochemical markers in patients with retinal vein occlusion and comparison in groups opposing the effectiveness of anti-VEGF therapy.Methods. 84 patients with macular edema were examined on the background of retinal vein occlusion, who underwent intravitreal injections of an angiogenesis inhibitor for therapeutic purposes. Further, depending on the effectiveness of treatment, the patients were divided into 2 groups, in which a retrospective comparative analysis of somatic status and laboratory data was performed.Results. It was shown that patients with occlusion of the retinal veins have significant impairments in terms of somatic status, blood biochemical parameters and coagulogram. Moreover, there is a direct relationship between the severity of somatic changes and ocular manifestations of the disease. The data obtained reflect a clear tendency in patients with occlusion of the retinal veins to a high risk of cardiovascular complications, including occlusive lesions. In patients with an insufficient treatment effect, a more severe course of arterial hypertension with an increased risk of stratification was detected.Conclusion. The somatic status and laboratory parameters of patients with retinal vein occlusion are significantly different from the norm, which must be taken into account in the prognosis of the course of an ophthalmologic disease.

Commentary on Down syndrome screening in China.

Prenatal screening for fetal Down syndrome has been widely practised in China for many years. In this special issue of BJOG, Tu et al. have published a systematic review on the performance of prenatal screening tests using biochemical and sonographic markers in Chinese women (Tu et al. BJOG 2016). Among the 78 included studies, of which most were from China, the majority (n = 64, 82%) were based on second-trimester biochemical markers. Although the pooled sensitivity and specificity for the second-trimester markers were 0.79 and 0.96, respectively, there were wide variations among individual studies. Most interestingly, 13 of the 64 second-trimester studies had a sensitivity of over 90%. Such an excellent performance has rarely been reported in studies from the non-Chinese population (Alldred et al. Cochrane Database Syst Rev 2012 Jun 13;(6):CD009925). This raised a concern over the quality of individual studies that warranted detailed analysis. In contrast, Li et al. reported in detail how to implement successfully a first-trimester combined screening (FTCS) programme for fetal Down syndrome in a resource-limited area of mainland China (Li et al. BJOG 2016). Despite the resource limitations, the author had followed strictly all the steps that were important for a successful screening programme, namely training and accreditation of staff, generation and use of local data, development of a customised cut-off and continuous quality assurance for both sonographers and biochemical assays. Specifically, the quality assurance steps included the following: (1) all sonographers were accredited by the Fetal Medicine Foundation and re-certified annually; (2) the performance of each sonographer was continuously monitored using a rolling standardised audit quality assurance report; (3) the multiple of the median values of individual biochemical markers were assessed monthly to determine the central tendency and dispersion; and (4) outcome data were followed-up. The above steps allowed early identification of deviation from expected performance for which early intervention could be initiated. Certification and quality assurance of sonographers is a particularly difficult process, requiring the support and cooperation of hospital administrators. It is interesting that in Li et al.'s study the cost of FTCS was quoted to be RMB800. Based on screening performance, noninvasive prenatal testing (NIPT) for fetal Down syndrome by cell-free DNA in maternal plasma is a far better test than FTCS, having a sensitivity and a specificity both above 99%. The cost of NIPT has come down substantially over the past 2 years. In China, NIPT is available in many major cities at a current user price most commonly between RMB2000 and 3000. It should not be long before the cost of NIPT is comparable to that of FTCS. At present, many hospitals in China are developing their own in-house NIPT platforms. This is a suboptimal move because such small hospital-based laboratories will not have enough volume to maintain a meaningful quality assurance programme. It is advisable that these screening programmes are coordinated within a region and centralised in one or a few centres where a strict quality assurance programme could be implemented. Even if NIPT has replaced conventional screening, the concept of ‘quality assurance’ as demonstrated in the study by Li et al. remains the key to the success for all screening programmes. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Routine Laboratory Blood Tests May Diagnose Significant Fibrosis in Liver Transplant Recipients with Chronic Hepatitis C: A 10 Year Experience.

Background and Aims: The aims of our study were to determine whether routine blood tests, the aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) and Fibrosis 4 (Fib-4) scores, were associated with advanced fibrosis and to create a novel model in liver transplant recipients with chronic hepatitis C virus (HCV). Methods: We performed a cross sectional study of patients at The University of California at Los Angeles (UCLA) Medical Center who underwent liver transplantation for HCV. We used linear mixed effects models to analyze association between fibrosis severity and individual biochemical markers and mixed effects logistic regression to construct diagnostic models for advanced fibrosis (METAVIR F3-4). Cross-validation was used to estimate a receiving operator characteristic (ROC) curve for the prediction models and to estimate the area under the curve (AUC). Results: The mean (± standard deviation [SD]) age of our cohort was 55 (±7.7) years, and almost three quarter were male. The mean (±SD) time from transplant to liver biopsy was 19.9 (±17.1) months. The mean (±SD) APRI and Fib-4 scores were 3 (±12) and 7 (±14), respectively. Increased fibrosis was associated with lower platelet count and alanine aminotransferase (ALT) values and higher total bilirubin and Fib-4 scores. We developed a model that takes into account age, gender, platelet count, ALT, and total bilirubin, and this model outperformed APRI and Fib-4 with an AUC of 0.68 (p < 0.001). Conclusions: Our novel prediction model diagnosed the presence of advanced fibrosis more reliably than APRI and Fib-4 scores. This noninvasive calculation may be used clinically to identify liver transplant recipients with HCV with significant liver damage.

Evaluation of early changes of cartilage biomarkers following arthroscopic meniscectomy in young Egyptian adults

BackgroundThe metabolic imbalance in the articular cartilage following meniscectomy includes an increase in cartilage degradation with an insufficient reparative or anabolic response resulting in structural, biochemical and mechanical changes that can progress from pre-clinical, to pre-radiographic, to radiographic damage of the joint. PurposeTo evaluate combinations of imaging and biochemical biomarkers for cartilage breakdown, synthesis and quantity in the early period of post-arthroscopic meniscectomy. Subjects and methodsTwenty young adults (three of them were females) who underwent unilateral arthroscopic partial meniscectomy were evaluated. The patients had a mean age of 32.5years (range, 24–39), mean BMI of 28.5kg/m2 (range, 24–34). Preoperative and six months postoperative US and MRI-based markers (cartilage thickness and volume, respectively) were quantified for medial and lateral tibio-femoral compartments for both knees. Preoperative, three and six months postoperative biochemical markers serum assays were measured; COMP and Col II (cartilage matrix breakdown) and PIICP (cartilage synthesis). These three markers were measured in an age, sex and BMI matched twenty healthy subjects for comparison. ResultsThe meniscectomized knees had significantly lower total knee cartilage volume, P<0.05 but non-significant mean thickness than the intact contralateral knees. Among the individual biochemical markers, PIICP had the highest significant diagnostic accuracy quantified as the area under the receiver-operator characteristics curve (AUC) of 0.75 (95% confidence interval: 0.509–0.912) higher than all others, P<0.05 to distinguish subjects with progressive cartilage loss from non-progressors. Diagnostically, ratio of COMP and Col II to PIICP scored AUC of 0.90 (0.69–0.98, higher than PIICP: P=0.0001). For prediction of cartilage loss, none of the individual markers could be used. ConclusionCartilage volume loss by MRI combined with changes in cartilage matrix turnover detected by molecular biomarkers may reflect the initial changes associated with cartilage degeneration that account for early OA.

Diagnosis of renal osteodystrophy among chronic kidney disease patients

AbstractOBJECTIVEThe purpose of this review was to study the prevalence of and establish an association between biochemical markers and the underlying rate of bone turnover in renal osteodystrophy.METHODSUsing the PubMed database, we undertook a systematic review of literature using studies that included bone histology in combination with serum biochemical markers among chronic kidney disease (CKD) patients, published between 1985 and 2007. Studies having at least 3 of 7 serum biochemical markers were chosen for this review.RESULTSOf the dialysis patients who were recipients of 1,701 bone biopsies, 41% had hyperparathyroid bone disease, 5% had osteomalacia, and 33% had adynamic bone disease. Among CKD patients not on dialysis, of a total of 1,316 bone biopsies, 34% had hyperparathyroid bone disease, 19% had osteomalacia, and 8% had adynamic bone disease. Dialysis patients who had high‐turnover bone disease compared with those with low bone turnover had significantly higher levels of parathyroid hormone, serum alkaline phosphatase, bone‐specific alkaline phosphatase, and osteocalcin. A similar relationship was observed among CKD patients not on dialysis. There was significant individual variation in bone turnover biochemical markers.CONCLUSIONSA combination of serum biochemical markers might predict underlying renal osteodystrophy better than would individual biochemical markers. A predictive model using bone histology and biochemical markers can be developed in the future.

Can biochemical markers serve as surrogates for imaging in knee osteoarthritis?

Osteoarthritis (OA) is a complex heterogeneous joint disease affecting more than 35 million people worldwide. The current gold standard diagnostic investigation is the plain radiograph, which lacks sensitivity. Biochemical markers have the potential to act as adjunct markers for imaging in the assessment of knee OA. We undertook this study to determine the association between individual biochemical markers and radiographic features, and to establish whether the association is strengthened when selected biochemical markers are combined into a single factor (a theoretical marker). Twenty serum and urinary biochemical markers were analyzed in 119 patients with predominantly tibiofemoral knee OA. Pearson's correlation was performed, and corresponding coefficients of determination (R(2)) were calculated to determine the association between biochemical markers and a range of imaging features from radiographs and dual x-ray absorptiometry of the knee. Biochemical markers demonstrating a significant association (P < 0.05) with a specific imaging feature were combined by principal components analysis (PCA). Pearson's correlation was repeated to establish whether the combined panel of biochemical markers showed a stronger association with imaging than the best single marker. Fourteen biochemical markers showed significant associations with one or more imaging features. By combining specific panels of biochemical markers to form factors, the association of markers with imaging features (R(2)) increased from 11.9% to 22.7% for the Kellgren/Lawrence (K/L) score, from 5.9% to 9.2% for joint space width (JSW), from 6.6% to 10.8% for sclerosis, from 13.5% to 22.6% for osteophytes, and from 12.0% to 14.2% for bone mineral density (BMD). Biochemical markers identifying patients with osteophytes overlapped with those correlated with a high K/L score, while markers of subchondral BMD formed a completely separate group. Biochemical markers of JSW included markers associated with both osteophytes and BMD. The PCA results suggest that biochemical marker combinations may be more sensitive than individual biochemical markers for reflecting structural damage in patients with knee OA. The differences in biochemical marker profiles associated with osteophytes compared with those associated with subchondral BMD raise the possibility that these 2 processes, commonly seen in bone in knee OA, have underlying biologic differences.

Female alcoholic outpatients and female college students: a correlational study of self-reported alcohol consumption and carbohydrate-deficient transferrin levels.

We sought to test the efficacy of two biochemical markers of alcohol consumption, gamma glutamyl transpeptidase and carbohydrate deficient transferrin, as indicators of heavy alcohol consumption in a female population. Using a sample of female outpatient alcoholics (n = 36) and a comparison group of female college students (n = 50), alcohol intake was monitored by self-report at approximately 90-day intervals over a period of 12 months. Gamma glutamyl transpeptidase (GGTP) and carbohydrate-deficient transferrin (CDT) values were determined for each sampling period. The criterion for heavy alcohol consumption was set at 140 g/alcohol/week for a 90-day period. Receiver operating characteristic (ROC) curves were plotted, area under the curve (Az) computed, and sensitivity and specificity calculated for both CDT and GGTP. ROC curves provide a graphical illustration of the association between the specificity and sensitivity of any diagnostic test over all possible cutpoint values. A significant, positive correlation between the amount of alcohol consumed and GGTP activity was recorded for the outpatient alcoholic group. Among the college students, there was a significant, positive correlation between CDT levels and alcohol consumed for the second reporting period. The sensitivity of the individual biochemical markers was low but, when used in combination, sensitivity was 66% and specificity, 80%. When a more stringent criterion for heavy alcohol consumption was applied (420 g/alcohol/week), the sensitivity of CDT actually decreased. CDT, used alone, is a poor indicator of heavy alcohol consumption in female subjects. When GGTP measures are used in conjunction with CDT, detection of heavy alcohol consumption may be enhanced to useful levels.

Bone density change and biochemical indices of skeletal turnover

Although biochemical markers of skeletal turnover cannot replace bone density scanning for the diagnosis of osteoporosis, it is thought that they may help add to prediction of fracture risk and help determine adequacy of osteoporosis therapy. Nevertheless, whether biochemical markers in the serum or urine can predict individual rates of bone loss in the spine or hip region is unknown. We studied a heterogeneous group of women (n = 81) who were premenopausal, untreated postmenopausal, and estrogen-treated postmenopausal with baseline determination of body mass index (BMI), calcium intake, biochemical measurements, and serial bone densitometry over 3 years. Serum assays included bone Gla protein (BGP), total and bone-specific alkaline phosphatase (AP, BSAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). Urine assays included hydroxyproline (OHP), calcium, total pyridinoline, and total deoxypyridinoline. Individual biochemical markers and calcium intake were modestly correlated with bone density changes but were inconsistent regarding the spine versus the hip. All of the formation variables were significantly correlated to spine density change (r = -0.24 to -0.49) whereas the only resorption variable that correlated was urine OHp/Cr (r = -0.31). The only formation variable that correlated with hip density change was serum PICP whereas all of the resorption variables except serum TRAP were correlated (r = -0.23 to -0.35). "High turnover" individuals were defined at those with levels of biochemical variables at least 1 SD above the mean young normal for each variable. Higher bone loss rates were seen in this group for several of the turnover markers compared with bone loss rates in all other individuals. However, the sensitivity of this "high turnover" status for identifying high bone losers did not exceed 60% for any of the variables. In untreated postmenopausal women, a model using urine OHp, serum ICTP, serum BSAP, and calcium intake was able to predict 42% of the variance of change in BMD of the lumbar spine. A model using BMI, serum ICTP, and serum BGP could predict 32% of the variance of change in BMD of the femoral neck. No combination of markers could predict variance in bone density change at either site in estrogenized women (premenopausal and estrogen-treated postmenopausal). We conclude that measuring individual serum and urine markers of bone turnover cannot accurately predict bone loss rates in the spine and hip; however, combinations of demographic and biochemical variables could predict some of the variance in untreated postmenopausal women. Biochemical markers cannot replace serial bone densitometry for accurate determination of change in bone mass at the most clinically relevant sites.