Fractional excretion of magnesium and kidney function parameters in nondiabetic chronic kidney disease.

AIM: Elevated fractional excretion of magnesium (FEMg) is a noninvasive biomarker of kidney damage, but its association with kidney functional parameters in nondiabetic chronic kidney disease (CKD) patients has not been sufficiently explored thus far. METHODS: We enrolled 111 adult patients with nondiabetic CKD and 30 controls. To precisely investigate kidney function, the following parameters were assessed measured glomerular filtration rate (mGFR), effective renal plasma flow (ERPF), Cystatin C, albuminuria, and fractional excretion of magnesium (FEMg). All the CKD patients were divided into two groups according to the values of mGFR (mL/min/1.73m2): the first group consisted of those with GFR≥ 60 mL/min/1.73m2, whereas the second group included those with GFR< 60 mL/min/1.73m2. RESULTS: FEMg (%) was significantly higher in the group of nondiabetic patients with CKD compared to the healthy subjects [6.3 vs. 5.3 %, P=0.013]. There was also significant difference in the value of FEMg between the first and second groups of CKD patients. Increased FEMg was significantly correlated with all the investigated kidney function parameters, mGFR, ERPF, Cystatin C and albuminuria (r=-0.62; r=-0.60; r=0.77; r=0.39; p<0.01 for all). In multiple regression analyses based on observed parameters of kidney function, only cystatin C was independently and significantly associated with FEMg (multiple correlation coefficients: 0.738, p < 0.001)). Nondiabetic CKD patients with GFR< 60 mL/min/1.73m2 have increased FEMg above 6.1% with 78.7 % specificity and 83.7% sensitivity. CONCLUSION: Highly significant association between kidney functional parameters and FEMg may indicate significance of this parameter in clinical practice.

Chronic Latent Magnesium Deficiency in Obesity Decreases Positive Effects of Vitamin D on Cardiometabolic Risk Indicators.

BACKGROUND: Obesity and micronutrient deficiencies contribute to the risk of cardiometabolic diseases such are type 2 diabetes mellitus and Cardiovascular Disease (CVD). OBJECTIVE: We examined the frequency of concomitant deficit of Magnesium (Mg) and vitamin D in obese patients and evaluated the connection of these combined deficiencies with indicators of cardiometabolic risk in non-diabetic subjects. METHODS: Non-diabetic middle aged adults (n = 80; mean age 36 ± 4 years, 52% women) were recruited based on weight/adiposity parameters [i.e. Body Mass Index (BMI) and body fat percentage (FAT%)]. Cardiometabolic risk indicators [insulin resistance (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)) and CVD risk (Framingham risk score for predicting 10-year CVD)], Mg status (i.e. total serum Mg concentration (TMg), Chronic Latent Mg Deficiency (CLMD) - 0.75-0.85 mmol/L), vitamin D status (i.e. serum concentration of 25-hydroxyvitamin D (25(OH)D), vitamin D deficiency <50 nmol/l) were assessed. RESULTS: Among obese subjects 36% presented a combination of vitamin D deficiency and CLMD. In all studied patients, 25(OH)D and TMg levels both, individually and combined, showed a negative linear correlation with HOMA-IR and CVD risk. In subjects with CLMD (TMg <0.85 mmol/L), a negative linear coefficient was found between 25(OH)D and, HOMA-IR and CVD risk, compared with subjects with normal TMg status (TMg ≥0.85 mmol/L). CONCLUSION: CLMD and vitamin D deficiency may commonly be present in obese non-diabetic subjects. Individually and combined, both deficiencies predispose non-diabetic patients to increased risk of cardiometabolic diseases. Maintaining normal Mg status may improve the beneficial effects of vitamin D on cardiometabolic risk indicators.

Vitamin D status and circulating biomarkers of endothelial dysfunction and inflammation in non-diabetic obese individuals: a pilot study.

INTRODUCTION: Obesity and inadequate vitamin D status are associated with endothelial dysfunction and cardiovascular disease. We evaluated the associations between vitamin D status (i.e. serum levels of 25-hydroxyvitamin D (25(OH)D)), biomarkers of endothelial dysfunction (i.e. serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin)), inflammatory markers (i.e. high-sensitivity C-reactive protein (hsCRP) and fibrinogen) and cardiometabolic risk factors. MATERIAL AND METHODS: Fifty obese (body mass index (BMI) ≥ 30 kg/m2) non-diabetic adults (mean age: 36.2 ±5.4 years) without pre-existing cardiovascular abnormalities and 25 clinically healthy, normal weight and age-matched individuals were included. Anthropometric parameters, markers of glucose and lipid metabolism, and serum levels of inflammatory and endothelial dysfunction biomarkers were assessed in all subjects. RESULTS: The mean serum 25(OH)D level was significantly lower in the obese group than in controls (33.5 ±15.2 vs. 60.1 ±23.1 nmol/l; p < 0.001). In the obese group, sE-selectin (36.4 (32.1-47.2) vs. 32.4 (24.6-35.5) ng/ml, p < 0.05) and hsCRP (6.0 ±3.4 vs. 3.5 ±1.0 mg/l, p < 0.05) were significantly higher in individuals with lower than median vitamin D levels (i.e. 31 nmol/l) compared with those with higher vitamin D levels. In multivariable linear regression analysis, hsCRP (ß = -0.43; p < 0.001) and sE-selectin (ß = -0.30; p = 0.03) were independently and significantly associated with serum 25(OH)D levels in the obese group. CONCLUSIONS: Vitamin D levels may be related to increased levels of biomarkers of endothelial dysfunction and inflammation in obese non-diabetic individuals.

Ceruloplasmin and antioxidative enzymes in pre-eclampsia.

OBJECTIVE: To evaluate diagnostic value of ceruloplasmin together with other enzymatic and nonenzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and uric acid) and to evaluate the level of oxidative stress in patients with pre-eclampsia (PE) and compare it with normal pregnancy. METHODS: In this prospective study, antioxidative markers were investigated in two groups of pregnant women: patients with pre-eclampsia (n = 32) and the healthy pregnant women (n = 60). The following antioxidative markers and enzymes were evaluated: serum ceruloplasmin levels, uric acid, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RESULTS: Serum levels of ceruloplasmin, uric acid and SOD were significantly higher in the PE group compared to the control group. Serum levels of GSH-Px were not significantly higher in the PE group compared to the control group. Serum ceruloplasmin and serum uric acid have the best diagnostic accuracy for oxidative stress in PE and are more accurate compared to antioxidative enzymes -SOD and specially more accurate than GSH-Px. CONCLUSIONS: Serum ceruloplasmin level may have significant role as the markers of oxidative stress in pre-eclampsia especially when used in combination with uric acid levels.

PLASMA ENDOTHELIN-1 LEVELS AND ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

INTRODUCTION: Microalbuminuria is a very important independent risk factor for the progression of renal diseases as well as diseases of the cardiovascular system. Pathophysiological mechanisms that lead to the development ofmicroalbuminuria in patients with diabetes are complex and they are a result of numerous factors. In the past decade, endothelin-1, the most potent vasoconstrictor peptide, was identified as animportant factor that significantly contributes to the functional and structural renal changes. The objective of this study was to investigate the relationship between plasma concentration of endothelin-1 and urinary albumin excretion in patients with type 2 diabetes mnellitus. MATERIAL AND METHODS: There were 76 patients with type 2 diabetes who were divided into those having normoalbuminuria (n-33), microalbuminuria (n=29) and macroalbuinuria (n=14), and 30 healthy controls. Plasma levels of endothelin-1 were measured by enzyme-linked immunosorbent assay. RESULTS: There were significant differences in plasma concentration of endothelin-1 among groups (P<0.01). The correlation between endothelin-1. albuminuria. proteinuria and glomercular filtration rate was significant. In multiple regression analyses the plasma concentration of endothelin-l was independently and significantly associated with albuminuria (ß=0.01, p=0.009), proteinuria =.02, p<0.001) and glon.erular filtration rate (P3=0ßl. pO-.P=)6).0Conclu- sion. Higher plasma concentrations of endothelin-1 are independently associated with the levels of urinary, excretion of albumin Whicw May morroborate tlse hpothesis of apotenstial role of this peptide inl th de- vepment of microalbUminuriauin diabetic necphrpathy.

Plasma endothelin-1 level, measured glomerular filtration rate and effective renal plasma flow in diabetic nephropathy.

BACKGROUND: Endothelin-1 (ET-1) is potent vasoconstrictor peptide which is able to contribute to the functional and structural renal changes. The aim of this study was to investigate the relationship between plasma concentration of ET-1 and indices of renal function in patients with diabetic nephropathy. METHODS: We measured plasma ET-1 levels in 99 patients with type 2 diabetes, divided into two groups according to the values of their glomerular filtration rate (GFR): group I (GFR ≥ 60 mL/min/1.73 m(2); n = 50), group II (GFR ≥ 60 mL/min/1.73 m(2), n = 49), and the control group (n = 30) with clinically healthy subjects who were matched by age and sex. GFR and effective renal plasma flow (ERPF) were measured by the radioisotopic clearance. Other renal function parameters, such as serum concentrations of cystatin C, urea, creatinine, uric acid, 24-h albuminuria and proteinuria were additionally measured. RESULTS: There were significant differences in plasma concentration of ET-1 among groups I, II and the control group (1.45 vs. 2.40 vs. 0.80 pg/mL, p < 0.001). The correlation between ET-1 and mGFR (r = -0.52, p < 0.001), ERPF (r = -0.42, p < 0.001), albuminuria and proteinuria (r = 0.36, p < 0.001; r = 0.48, p < 0.001) and cystatin C (r = 0.42, p < 0.001) was significant. In multiple regression analyses, only plasma concentration of ET-1 (p < 0.001) and duration of hypertension (p < 0.05) were independently and significantly associated with mGFR. CONCLUSION: A higher plasma concentration of ET-1 is independently associated with a decreased value of GFR in patients with diabetic nephropathy.

Reticulated platelets and antiplatelet therapy response in diabetic patients.

Increased platelet turnover and high level of reticulated platelets are associated with low response to antiplatelet therapy in diabetes mellitus type 2. This study evaluated association between percentage of reticulated platelets (%RP) and the response to antiplatelet therapy in patients with type 2 diabetes mellitus (T2DM). This prospective, pilot, case-control, clinical trial included 79 subjects stratified in three groups: group I included 30 patients with T2DM, group II included 34 non-diabetic patients and 15 healthy age and sex matched healthy volunteers were enrolled in control group. Platelet response to clopidogrel and aspirin was assessed by Multiplate(®) aggregometry analyzer. Individual response to dual antiplatelet therapy was estimated by the percentage of decrease in overall platelet aggregability (%DPA) obtained after antiplatelet therapy, calculated by presented formulas: %DPAadp = 100 × (1 - ADP/TRAP) and %DPAaspi = 100 × (1 - ASPI/TRAP). %RP was significantly higher in diabetics, than in non-diabetics, (3.17 ± 1.26 vs. 2.39 ± 1.56; p < 0.05). Significantly lower response to clopidogrel (31.55 ± 13.02 vs. 50.24 ± 11.38; p < 0.001) and aspirin (52.33 ± 22.67 vs. 64.31 ± 16.47; p < 0.05) therapy was observed in diabetics. %RP negatively correlated with response to clopidogrel therapy, but positively with metabolic profile indicators in diabetics (p < 0.05, all). Correlation of %RP with metabolic profile indicators and poor response to antiplatelet therapy suggest that altered metabolic profile can affect platelet turnover in T2DM leading to low responsiveness to antiplatelet therapy in these patients.

The effect of angiotensin converting enzyme inhibition on effective renal plasma flow in patients with diffuse renal parenchymal diseases and hypertension.

INTRODUCTION: Angiotensin converting enzyme inhibitors are commonly used to treat various hypertensive conditions and in addition to lowering blood pressure these drugs affect the local renal hemodynamic status, thereby influencing the glomerular filtration rate and effective renal plasma flow. The study was aimed at determining whether angiotensin converting enzyme inhibitors can produce significant changes in effective renal plasma flow in patients with parenchymal renal disease and to assess whether the changes depend on the pre-existing functional status of the kidney. MATERIAL AND METHODS: The study included 80 subjects, 40 subjects with hypertension associated with diffuse renal parenchymal disease and 40 subjects with essential hypertension. All study subjects underwent the baseline effective renal plasma flow measurement and the repeated effective renal plasma flow measurement after administration of captopril. Effective renal plasma flow was determined by 131 I-hippuran clearance in blood samples taken at 20 and 30 minutes. RESULTS: Angiotensin converting enzyme inhibitors caused significant effective renal plasma flow changes in 55% of subjects with diffuse renal parenchymal disease and in 75% of subjects with essential hypertension. The effective renal plasma flow changes were more significant in subjects with preserved renal function (normal baseline effective renal plasma flow) compared to subjects with reduced baseline effective renal plasma flow. CONCLUSION: The application of angiotensin converting enzyme inhibitors in patients with diffuse renal parenchymal disease and in individuals with essential hypertension may result in significant hemodynamic changes in the kidney, accompanied by changes in effective renal plasma flow. The extent of the changes caused by angiotensin converting enzyme inhibitors depends on the preexisting functional status of the kidney.

Changes of serum VEGF concentration after intravitreal injection of Avastin in treatment of diabetic retinopathy.

PURPOSE: Avastin (bevacizumab) intravitreal injections are widely used for treatment of diabetic retinopathy. The aim of our study was to analyze effect of 1.25 mg of intravitreal Avastin on serum concentration of vascular endothelial growth factor (VEGF) in diabetic patients. METHODS: Participants were 10 diabetic patients on insulin therapy, without any other eye or systemic disease, and no kidney disfunction. Both eyes of diabetic patients were injected simultaneously with 1.25 mg of intravitreal Avastin, as a first step in treatment of nonproliferative diabetic retinopathy with clinically significant macular edema (4 patients), and of proliferative diabetic retinopathy (6 patients). Fluorescein angiography was performed prior to and laser therapy followed 1 month after Avastin treatment. VEGF concentration in patients serum was measured by ELISA technique: on the day of the Avastin administration, and 1, 7, and 28 days after intravitreal injection. RESULTS: In all analyzed participants, 24 hours after Avastin treatment, serum levels of VEGF were lower then basal (preinjection value). Maximal reduction of serum VEGF was noted on the 7th postoperative day. Twenty-eight days after, VEGF level in serum was raised, without completely reaching basal preoperative concentrations in most patients. CONCLUSIONS: Intravitreal injections of anti-VEGF drugs have an effect on decreasing systemic VEGF values. Rhythm of changes in serum VEGF concentrations and lowest detected concentration on the seventh postinjection day are according to pharmacokinetics of Avastin in serum and vitreous, reported by similar studies. The small number of patients involved in this pilot study implicates the need for further studies.

Evaluation of lipid parameters and bioindices in patients with different stages of chronic renal failure.

BACKGROUND/AIM: Cardiovascular morbidity and mortality are markedly increased in chronic renal failure (CRF). The aim of this study was to evaluate lipid parameters and bioindices in patients with different stages of CRF. METHODS: In 46 hemodialysed (HD), 50 CRF patients with II, III and IV stage of CRF (non-HD) and 48 control subjects triglycerides (TG), total cholesterol (C), HDL-C, urea, creatinine, creatinuria (standard biochemical methods), apolipoprotein (apo) AI, apo B, lipoprotein(a), cystatin C (immunoturbidimetric method) were evaluated, and LDL-C, non-HDL-C, LDLC/HDL-C, non-HDL-/HDL-C, TG/HDL-C, and new bioindices, LTI (lipid tetrad index), logLTI, LPI (lipid pentad index), logLPI, AIP (atherogenic index of plasma), and creatinine clearance were calculated. RESULTS: There were significant differences in the levels of TG, HDL-C, LDL-C, non-HDL-C, total C and apo A-I between the HD and non-HD patients, and the HD patients and the controls. LTI and LPI were significantly higher in the HD and non-HD patients compared to the controls (p < 0.05), without a good separation by the Box-Whisker plots. The values of TG/HDL-C ratio and AIP were significantly higher in the HD and nonHD-patients compared to the controls (p < 0.05), and significantly higher in the HD compared to non-HD patients (p < 0.05). AIP > 0.11 was found in 71.7% of the HD, 56% of non-HD and 31.3% of the controls. CONCLUSION: Among lipid parameters and indices, AIP and TG/HDL-C ratio are most suitable for evaluation of lipid disturbances in different stages of CRF. In addition to, non-HDL-/HDL-C, and apoB/A-I ratios, apo A-I, HDL-C and TG are important markers in HD patients. Non-HDL-C is not a suitable marker. LTI and LPI need to be further investigated.

Cystatin C in pre-eclampsia.

OBJECTIVE: To evaluate diagnostic value of cystatin C serum levels as alternative marker of renal function in pre-eclamsia (PE) and compare it with the traditional markers of renal function, creatinine and uric acid. In order to investigate the possible influence of inflammation on biochemical markers of renal function, serum levels of high sensitive CRP were measured (hsCRP). METHODS: In this prospective study markers of kidney function were investigated in two groups of pregnant women: one with PE (n = 32) and the other of healthy pregnant women (n = 60). Serum cystatin C levels were measured as well as levels of traditional renal markers creatinin and uric acid and levels of high sensitive C-reactive protein. RESULTS: Serum levels of cystatin C, creatinine and uric acid were significantly higher in the PE group than in the control group. Serum levels of hsCRP were higher in approximately the same number of patients with PE (50%) as in normal pregnancies (40%), without significant differences in CRP values between the two groups of patients. CONCLUSIONS: Cystatin C serum level may have significant role as a marker of pre-eclampsia specially when used in combination with uric acid levels.

[The role of holotranscobalamin in examination of vitamin B12 status].

INTRODUCTION: Holotranscobalamin contains biologically available cobalamin because only holotranscobalamin promotes the uptake of the cobalamin therein by all cells, via specific receptors. Therefore holotranscobalamin has been proposed as a potentially useful alternative indicator of vitamin B12 status. The aim of the present study was to assess usefulness of holotranscobalamin in the evaluation of vitamin B12 status. MATERIAL AND METHODS: We examined serum level of holotranscobalamin in 135 subjects divided in four groups according to the serum concentration of vitamin B12: 30 subjects with vitamin B12 <154 pmol/l, 50 subjects with vitamin B12 154-250, 30 subjects with vitamin B12 2251-350 pmol/l, 25 subjects with vitamin B12 >350 pmol/l. RESULTS: The results show that in subjects with low vitamin B12 serum level there are those with normal holotranscobalamin concentration (60%) and that in subjects with normal vitamin B12 there are those with low holotranscobalamin concentration (22%). The obtained results also show positive significant correlation between levels of holotranscobalamin and vitamin B12 (r = 0.62, p < -0.001). CONCLUSION: We can conclude that biologically active cobalamin, holotranscobalamin, is a useful tool when examining vitamin B12 status especially in subjects with borderline and low vitamin B12 concentrations. Measurements of the serum holotranscobalamin may be superior to total serum cobalamin.

[Laboratory medicine today].

INTRODUCTION: Laboratory medicine today is a well-established branch of medicine which has an important role in improving of diagnostics, research and all forms and levels of education at the Faculty of Medicine in Novi Sad. The value of laboratory medicine is particularly important in team work within the Clinical Center of Novi Sad, nowadays - Clinical Center of Vojvodina. INSTITUTE OF LABORATORY MEDICINE OF THE CLINICAL CENTER OF VOJVODINA: The institute of Laboratory Medicine of the Clinical Center of Vojvodina is a contemporary organized, integrated system of laboratories, employing highly educated professional staff and with the exception of the nuclear-medicine laboratory, has all necessary equipement for providing the highest level of laboratory diagnostics. The Institute is a part of the international RIQAS (Randox International Quality Assessment Scheme) quality control and in the process of getting and accreditation. Today, the Institute offers a variety of over 400 different laboratory analyses and functional tests. The capacity of laboratory services is being significantly increased and is permanently growing. In addition, it is necessary to establish a PCR laboratory and a Department of Microbiology. CONTEMPORARY TRENDS IN ORGANIZATION OF LABORATORY SERVICES: The Institute of Laboratory Medicine is also engaged in research, publishing and projects. It is a teaching hospital for the Department of Pathophysiology. This kind of approach to education of medical students ensures that pathophysiology provides a solid foundation for clinical studies at the Faculty of Medicine in Novi Sad.

[The importance of homocysteinemia measurement in chronic renal failure].

INTRODUCTION: Hyperhomocysteinemia is an independent risk factor for premature cardiovascular disease. In this study we examined the prevalence of high plasma levels of homocysteine in different stages of chronic renal failure. MATERIAL AND METHODS: We examined 105 subjects: 73 patients in different stage of chronic renal failure, 31 of them on hemodialysis, and 32 subjects as a control group. RESULTS: The results show high prevalence of hyperhomocysteinemia in chronic renal failure patients, especially with reduction of glomerular filtration rate over 50% of the surface normalized value. CONCLUSION: We can conclude that hyperhomocysteinemia is important risk factor for cardiovascular diseases in chronic renal failure patients, according to its high prevalence in these patients.

Tubulointerstitial dysfunction in early post-transplant period.

Dysfunction of a transplanted kidney may develop at any time in the post-transplant period. The aim of this study was to differentiate levels of early dysfunction of a transplanted kidney. The study included 45 examinees undergoing kidney transplantation. They were divided into four groups, in regard to length of hospitalization and post-transplant complications: group I (up to 15 days, complication-free); group II (up to 15 days, with complications); group III (up to 30 days); group IV (up to 60 days). The control group included patients undergoing abdominal surgery, without uropoetic system disorders. The following parameters were examined on a daily basis a month after transplantation on average: creatinine clearance, creatinine and urea. Statistical analysis of these parameters revealed the following levels of renal dysfunction: control group--circulatory tubular dysfunction without azotemia; group I--polyuric acute tubular necrosis; group II and group III--severe or moderately severe polyuric acute tubular necrosis and group IV--polyuric acute tubular necrosis.