Cardiovascular Biomarkers in Chronic Kidney Disease
Cardiovascular morbidity and mortality are markedly increased in chronic renal failure patients. Although it cannot be regarded as a cardiovascular disease risk equivalent, kidney dysfunction is considered an independent predictor of increased cardiovascular risk that increases with deteriorating kidney function. The association is a very complex one, and the term cardiorenal syndrome is now widely used. Cardiovascular disease in chronic kidney disease patients usually manifests as ischemic heart disease (in the form of angina, acute coronary syndrome or sudden cardiac death), cerebrovascular disease, peripheral vascular disease, and congestive heart failure. Vascular disease includes atherosclerosis and vascular calcifications, and cardiomyopathy comprises left ventricular hypertrophy, cardiac fibrosis and left ventricular systolic and diastolic dysfunction. In addition to the well-established traditional risk factors such as hypertension, hyperlipidemia, insulin resistance and diabetes mellitus, the association is supported by synergistic action of non-traditional risk factors such as excessive calcium-phosphorus load, hyperparathyroidism, anemia, hemodynamic overload, malnutrition, inflammation, hyperhomocysteinemia, altered nitric oxide synthase and increased oxidative stress. This paper summarizes the current understanding of the significance of specific uremic retention solutes, natriuretic peptides, biochemical markers of disorders in calcium-phosphorus homeostasis, systemic inflammation, oxidative stress, and dyslipidemia.
Testing of IQ™ 200 Automated Urine Analyzer Analytical Performances in Comparison with Manual Techniques
Automation is necessary in laboratory systems. It enables reduction of time required for sample analysis, as well as standardization of methods. However, automation of urine control in laboratories is much less common than in hematological analyses. Not long ago, the necessary automated systems for urine analysis have also been developed. The objective of this study is a comparison of the IQ™ 200 automated system for urine analyzing with standardized manual urine analyzing techniques. Comparative analysis of 300 samples was performed by the IQ™ 200 system and by the standardized methods of manual microscopy and chemical urine analysis. The results acquired point to very high compatibility between urine analyses by manual techniques and by the automated system IQ™ 200, and in some analyses IQ™ 200 showed higher sensitivity. It can be concluded, with the aim of standardization and shortening of time required for urine analysis, that utilization of automated urine analyzing systems is recommendable, especially in institutions with a large number of daily analyses. This is also supported by the fact that operation procedure on automated systems is much more simple in comparison to manual techniques.
Velibor Čabarkapa, Zoran Stošić, Radmila Žeravica, Branislava Ilinčić and Ana Filipović
The Importance of Holotranscobalamin Measurement
Clinically significant vitamin B12 deficiency can occur even with total vitamin B12 levels apparently within normal range. There is an indeterminate zone between approximately 154 and 300 pmol/L of vitamin B12 where there is likely misclassification of B12 status if relying on total serum B12. The aim of the present study was to assess the usefulness of holotranscobalamin in diagnosis of B12 deficiency. Blood samples were collected and subjected to assays for vitamin B12 and holotranscobalamin. We examined the levels of holotranscobalamin in 32 subjects (n=32, f=18, m=14) with vitamin B12 values within interval 154-300 pmol/L. These subjects were compared with control group with vitamin B12>300 pmol/L (n=31, f=17, m=14). 25% of subjects with vitamin B12 of 154 to 300 pmol/L had low levels of holotranscobalamin. Holotranscobalamin levels of patients with vitamin B12 of 154 to 300 pmol/L were significantly lower than those of control subjects (38.55 ± 23.0 vs. 61.35 ± 31.81 pmol/L, p<0.01). The obtained results also show a positive significant relationship between levels of holotranscobalamin and vitamin B12 (r=0.53, p<0.01). In conclusion, holotranscobalamin is a better indicator of early vitamin B12 deficiency than total serum cobalamins and it is a useful tool in the diagnosis of vitamin B12 deficiency.
Sunčica Kojić-Damjanov, Mirjana Đerić, Nevena Eremić and Velibor Čabarkapa
The Influence of Chronic Helicobacter Pylori Infection on some Serum Lipid Profile Parameters, Apolipoproteins A-I and B and Lp(a) Lipoprotein
Data on proatherogenic lipid profile alterations due to chronic Helicobacter pylori (HP) infection are contradictory. Aim of this study was to examine the differences in some lipid parameters between 55 subjects of both gender with a chronic HP infection (IgG>50 U/mL and IgA <20 U/mL) and 55 gender matched HP seronegative subjects (IgG and IgA <20 U/mL). Total cholesterol (TC) (p<0.001), triglycerides (TG) (p<0.05), LDL-cholesterol (LDL-C) (p<0.02), non-HDL-cholesterol (non-HDL-C), apolipoprotein (apo) B (p<0.001), Lp(a) and HDL-cholesterol (HDL-C) serum levels were higher in HP seropositive than in seronegative subjects, while there were almost no differences in apo A-I. In HP seropositive subjects, the frequency of pathological TC (p<0.001), TG (p<0.05), LDL-C (p<0.01), non-HDL-C (p<0.01), apo B (p<0.02) and Lp(a) serum levels was higher compared to seronegative. Serum HP IgG titers correlated negatively with TC, LDL-C (p<0.05), non-HDL-C, apo B and Lp(a) levels, and positively with TG, HDL-C and apo A-I levels. Results are similar for both genders. Our results confirm the hypothesis that a chronic HP infection could modify the lipid profile in a proatherogenic way.
Velibor Čabarkapa, Zoran Stošić, Radmila Žeravica and Branislava Ilinčić
Hyperhomocysteinemia in Chronic Renal Insufficiency
Hyperhomocysteinemia is an independent risk factor for premature cardiovascular disease. Since the homocysteine level is elevated in patients with advanced chronic renal insufficiency, it has been presented as an important factor contributing to the development of cardiovascular complications in these patients. In this study we examined the level of homocysteine in patients with mild-moderate degree of glomerular filtration rate reduction (creatinine clearance >40 mL/min and <80 mL/min/1.73 m2). Thirty patients (f=15, m=15) were compared with healthy subjects (n=32, f=17, m=15). Blood samples were collected and subjected to assays for homocysteine, creatinine, creatinine clearance. The results show that homocysteine levels of patients were significantly higher than those of healthy subjects (12.75 ± 3.9 vs. 8.5 ± 1.75 μmol/L, p<0.001). The obtained results also show a significant negative relationship between the level of homocysteine and creatinine clearance (r=-0.8). In conclusion, hyperhomocysteinemia is a common finding not only in advanced chronic renal insufficiency, but also in patients with mild-moderate reduction of glomerular filtration rate, and may significantly contribute to premature development of cardiovascular complications.
Sunčica Kojić-Damjanov, Mirjana đerić, Velibor Čabarkapa and Ljiljana Vučurević-Ristić
Significance of Determining Levels of Apolipoproteins A-I and B in the Diagnostics and Assessment of Lipid-Related Atherogenic Risk in Hyperalpha-Lipoproteinemia, Hypocholesterolemia and Hypo-Hdl-Cholesterolemia
The significance of determining apolipoproteins apoB and apoA-I and their correlation with lipid status parameters were tested in hyperalpha-lipoproteinemia (30 women), hypocholesterolemia (10 men) and hypo-HDL-cholesterolemia (15 women and 21 men). Control groups were 20 normolipidemic men and women, each. ApoA-I showed positive correlation with HDL-cholesterol in hyperalpha-lipoproteinemia, with total and HDL-cholesterol in hypocholesterolemia, and with total and LDL-cholesterol in females with hypo-HDL-cholesterolemia, and negative correlation with cholesterol ratios only in hypocholesterolemia. ApoB showed a positive correlation with total and LDL-cholesterol in all groups, and with cholesterol ratios in hyperalpha-lipoproteinemia and hypo-HDL-cholesterolemia. The apoB/apoA-I ratio, correlating with the majority of lipid parameters, and with the highest percentage of pathological values in all tested groups, was singled out as the most sensitive parameter for the evaluation of lipid-related atherogenic risks.
Mirjana Đerić, Sunčica Kojić-Damjanov, Velibor Čabarkapa and Nevena Eremić
Biochemical Markers of Atherosclerosis
This paper is a brief review of some lipid parameters and serum markers of inflammation in a view of their predictive relevance for the atherosclerotic disease. A discourse on the importance of measuring different lipids and lipoproteins, concentration of LDL particles and apolipoprotein levels is still underway. Also, the recommendations for apolipoprotein (a), phenotypization and other lipid markers have not yet been established. In recent years the recommendations imply simultaneous measuring of multiple markers and calculating the lipid index values such as lipid tetrad index (LTI), lipid pentad index (LPI) and atherogenic index of plasma (AIP). Several circulating markers of inflammation such as C-reactive protein, serum fibrinogen and elevated leukocyte number, are consistently associated with atherosclerosis. In spite of a lack of evidence on measuring the C-reactive protein in a wide population, the guidelines for its application in diagnostics and therapy of coronary heart disease were developed. Some proinflammatory cytokines, adhesion molecules and markers of leukocyte activation are promising markers, requiring, however, more detailed prospective evaluation. The question to be elucidated is if these inflammatory markers are directly involved in the pathogenic process.
Velibor Čabarkapa, Branislava Ilinčić, Mirjana Đerić, Isidora Radosavkić, Mirko Špovac, Jan Sudji and Veljko Petrović
Background: Chronic kidney disease (CKD) is one of the most significant global health problems accompanied by numerous complicatons, with constant increase in the number of affected people. This number is much higher in early phases of disease and patients are mostly asymptomatic, so early detection of CKD is crucial. The aim was examination of the prevalence of CKD in the general population of males in Vojvodina, based on estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR), and exploring the determinants and awareness of CKD.
Methods: This cross-sectional study included 3060 male examinees from the general population, over 18 years of age, whose eGFR and ACR were calculated, first morning urine specimen examined, arterial blood pressure measured and body mass index calculated. Standard biochemistry methods determined creatinine, urea, uric acid and glucose serum concentrations as well as albumin and creatinine urine levels.
Results: Prevalence of CKD in the adult male population is 7.9%, highest in men over 65 years of age (46.7%), while in the other age groups it is 3.6-12.6%. The largest number of examinees with a positive CKD marker suffer from arterial hypertension (HTA) and diabetes mellitus (DM). Only 1.3% of examinees with eGFR<60 ml/min/1.73 m2 and/or ACR≥ 3 mg/mmol had been aware of positive CKD biomarkers.
Conclusions: Obtained results show the prevalence of CKD in adult males is 7.9%, HTA and DM are the most important CKD risk factors and the level of CKD awareness is extremely low (1.3%) indicating the necessity for introduction of early stage disease recognition measures, including raising CKD awareness.
The Importance of Free Light Chains of Immunoglobulins Determination in Serum
For many years, Bence Jones proteinuria has been an important diagnostic marker for multiple myeloma. Relatively new serum tests for free kappa and free lambda light chains of immunoglobulins reflect the production of free light chains more accurately than urine tests. In this study, we examined the value of serum free light chains measurement in the diagnosis of some neoplastic diseases and the discrepance between the findings of serum protein electrophoresis and serum free light chains. Thirty one patients (f=19, m=12) were included in the study, most of them with blood malignant diseases. The results show that in six patients with normal gamma and beta electrophoresis fractions there are abnormal levels of free light chains and/or an abnormal κ/LD ratio. In 20 patients we found an abnormal κ/LD ratio, and in 21 patients we found an abnormal κ or LD level, or both. The obtained results show the important role of serum free light chains determination in identifying patients with monoclonal gammopathies.
Velibor Čabarkapa, Romana Mijović, Zoran Stošić, Nikola Ćurić, Radmila Žeravica and Branislava Ilinčić
Estimation of Glomerular Filtration Rate From Serum Cystatin C and Creatinine in Patients with Thyroid Dysfunction
Given that thyroid function influences serum cystatin C and creatinine levels, the question arises as to whether it is possible to accurately estimate glomerular filtration rate (GFR) in patients with thyroid dysfunction. The objective of the study was to determine serum cystatin C and creatinine levels and estimate GFR in patients with thyroid dysfunction. The study included 32 cases with newly diagnosed hyperthyroidism and 27 cases with newly diagnosed hypothyroidism, as well as 20 healthy controls matched for sex and age with the cases. Serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4), creatinine and cystatin C were measured in all study subjects. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C-based equations. Serum cystatin C levels were significantly higher in hyperthyroid subjects compared to controls (1.32±0.31 vs. 0.89±0.15; p<0.01). Serum creatinine levels were significantly lower in hyperthyroid subjects compared to controls (60.6±10.2 vs. 76.4±8.6; p<0.01), and significantly higher in hypothyroid subjects compared to controls (94.5±13.2 vs. 76.4±8.6; p<0.01). GFR estimated with the MDRD equations was significantly higher in hyperthyroid subjects compared to hypothyroid subjects (101.6±20.7 vs. 64.1±11.6 mL/min/1.73m2; p<0.01). GFR estimated with the equation based on serum cystatin C was significantly lower in hyperthyroid subjects compared to hypothyroid subjects (59.2±22.1 vs. 92.1±16.0 mL/min/1.73m2; p<0.01). Although serum cystatin C is regarded a reliable marker of GFR and more sensitive than serum creatinine, it has limitations in patients with thyroid dysfunction, due to significant changes in its serum concentrations regardless of renal function. In patients with thyroid dysfunction GFR should therefore be estimated using the equations based on serum creatinine.