Effects of dietary milled seed mixture on fatty acid status and inflammatory markers in patients on hemodialysis.

BACKGROUND: Plant seeds have gained interest for their health benefits due to their fatty acid content. The objective of this study was to determine the effects of dietary consumption of milled sesame/pumpkin/flax seed mixture on glycemic control, serum lipids, phospholipid fatty acid status, and inflammatory factors in patients on hemodialysis. METHODS: Thirty patients with well nutrition status (18 male, 12 female) were enrolled in the study. Participants consumed 30 g of milled sesame/pumpkin/flax (6 g/6 g/18 g, resp.) seeds mixture added to their habitual diet. RESULTS: Total n-6 and n-3 polyunsaturated fatty acids and levels of linoleic, dihomo-gamma-linolenic (DGLA), arachidonic, alpha-linolenic (ALA), eicosapentaenoic, docosapentaenoic, and docosahexaenoic (DHA) acid were increased after 12 weeks of supplementation. A significant decrease of the serum triglyceride level (P < 0.001), glucose, insulin, calculated IR HOMA (P < 0.05), and inflammatory markers (TNF-alpha, IL-6, and hs-CRP, P < 0.001) was observed after seed mixture treatment. The serum levels of CRP and TNF-alpha negative correlate with ALA, DHA, and DGLA. CONCLUSION: Results of this study indicated that dietary milled sesame/pumpkin/flax seed mixture added to a habitual diet lowered triglyceride and CRP, TNF-alpha, IL-6 levels, affect glycemic control and improved fatty acid profile and pruritus symptoms in hemodialysis patients.

Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients.

Diabetes and renal insufficiency are interrelated metabolic disorders closely associated with redox homeostasis disturbances. The aim of this study was to compare the activity of copper zinc superoxide dismutase (CuZnSOD) in the erythrocytes of hypertensive diabetic patients with or without renal insufficiency with normal healthy control subjects. In both groups of diabetic patients, blood glucose level and the content of glycosylated hemoglobin (HbA1c) were higher than in the control group. However, CuZnSOD activity was significantly higher than control only in hypertensive diabetic patients with renal insufficiency. Our results suggest that disturbances in superoxide homeostasis do correlate with long-term complication in diabetes, i.e. diabetic renal insufficiency and hypertension.

Screening of elderly for chronic kidney disease.

BACKGROUND AND AIMS: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years--one without and the other with hypertension. METHODS: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertension. Data on patients were obtained by interview, analysis of medical records and physical examinations. Serum and urine creatinine, proteinuria, microalbuminuria (MAU, turbidimetry), and urinary sediment were analyzed. RESULTS: Among the 585 patients, there were 54.5% with a positive family history for hypertension and 14% for kidney diseases. MAU was significantly more frequent (30 vs. 11%) and the mean estimated glomerular filtration rate (eGFR) higher (71 ± 14 vs. 64 ± 14 ml/min/1.73 m) in patients without hypertension than in those with hypertension. The majority of patients with stage 3 CKD had eGFR >45 ml/min/1.73 m(2) with normal urinary findings. Multivariate logistic regression analysis found age and treatment with angiotensin-converting enzyme inhibitors to be associated with reduced eGFR, MAU and proteinuria. In addition, smoking was associated with eGFR, but a family history for kidney disease and belonging to the group without hypertension were associated with MAU. CONCLUSION: The high prevalence of markers for CKD in symptomless elderly without hypertension confirmed that the elderly, as a high-risk population, should be screened based on increased age alone.

Association of blood pressure and metabolic syndrome components with magnesium levels in drinking water in some Serbian municipalities.

Chronic exposure to insufficient levels of magnesium (Mg) in drinking water increases the risk of magnesium deficiency and its association with hypertension, dyslipidemia and type 2 diabetes mellitus. The aim of the study was to assess the potential association of mineral contents in drinking water with blood pressure and other components of metabolic syndrome (MetS) (BMI as measure of obesity, triglycerides, glucose, and insulin resistance, index-HOMA IR), in a healthy population. This study was conducted in three randomly selected municipalities (Pozarevac, Grocka and Banovci), and recruited 90 healthy blood donors, aged 20-50 years. The Pozarevac area had a four times higher mean Mg level in drinking water (42 mg L(-1)) than Grocka (11 mg L(-1)). Diastolic blood pressure was lowest in subjects from Pozarevac. Serum Mg (sMg) was highest, and serum Ca(2+)/Mg (sCa/Mg) lowest in subjects from Pozarevac, and after adjustment for confounders (age, gender, BMI), only total cholesterol and sMg levels were independent predictors of diastolic blood pressure, sMg levels were independent predictors of triglycerides, and sCa/Mg predicted glucose levels. These results suggest that Mg supplementation in areas of lower magnesium levels in drinking water may be an important measure in the prevention of hypertension and MetS in general.

Early detection of chronic kidney disease: collaboration of Belgrade nephrologists and primary care physicians.

BACKGROUND: Belgrade screening study was undertaken in order to detect persons with CKD markers in at risk populations and to educate primary care physicians how to carry out CKD screening. METHODS: The study was performed by primary care physicians from thirteen Belgrade health centers in collaboration with nephrologists from clinical centers. Subjects without previously known kidney disease were enrolled: 1316 patients with hypertension without diabetes, 208 patients with type 2 diabetes and 93 subjects older than 60 years without hypertension or diabetes. The survey consisted of an interview, consisted of an interview, estimation of glomerular filtration rate (eGFR-MDRD), single urine dipstick detection of proteinuria, hematuria, glucosuria, microalbuminuria. RESULTS: Microalbuminuria with or without proteinuria in combination with eGFR>60 ml/min/1.73 m2 was detected in 17% , 41% and 24% of patients with hypertension, diabetes and those above 60 years, respectively. Reduced eGFR (<60 ml/min/1.73 m2 ) was found in 23%, 12% and 22% of the same patient groups. The prevalence of CKD markers increased with increasing number of risk factors. CONCLUSION: High prevalence of CKD markers in at risk population detected by primary care physicians in this collaborative study seems to be the best way to encourage primary care physicians to carry out regular CKD screening.

Early detection of chronic kidney disease: Collaboration of Belgrade nephrologists and primary care physicians

Background: Belgrade screening study was undertaken in order to detect persons with CKD markers in at risk populations and to educate primary care physicians how to carry out CKD screening. Methods: The study was performed by primary care physicians from thirteen Belgrade health centers in collaboration with nephrologists from clinical centers. Subjects without previously known kidney disease were enrolled: 1316 patients with hypertension without diabetes, 208 patients with type 2 diabetes and 93 subjects older than 60 years without hypertension or diabetes. The survey consisted of an interview, consisted of an interview, estimation of glomerular filtration rate (eGFR-MDRD), single urine dipstick detection of proteinuria, hematuria, glucosuria, microalbuminuria. Results: Microalbu minuria with or without proteinuria in combination with eGFR>60 ml/min/1.73m2 was detected in 17% , 41% and 24% of patients with hypertension, diabetes and those above 60 years, respectively. Reduced eGFR (<60 ml/min/1.73m2 ) was found in 23%, 12% and 22% of the same patient groups. The prevalence of CKD markers increased with increasing number of risk factors. Conclusion: High prevalence of CKD markers in at risk population detected by primary care physicians in this collaborative study seems to be the best way to encourage primary care physicians to carry out regular CKD screening (AU)

Antecedentes: El estudio de Belgrado se realizó para detectar personas con marcadores de ERC en poblaciones de riesgo y formar a los especialistas de atención primaria sobre cómo realizar proyecciones de ERC. Métodos: El estudio fue realizado por especialistas de atención primaria de trece centros de salud en colaboración con nefrólogos de centros clínicos. Se incluyó a personas sin enfermedad renal previa conocida: 1316 pacientes con hipertensión sin diabetes, 208 pacientes con diabetes tipo 2 y 93 pacientes de más de 60 años sin hipertensión ni diabetes. El estudio consistía en una entrevista, determinación de la tasa de filtración glomerular estimada (TFGe-MDRD) y detección de proteinuria, hematuria, glucosuria y microalbuminuria con una única tira reactiva de orina. Resultados: Se detectó microalbuminuria con o sin proteinuria en combinación con una TFGe >60 ml/min/1,73m2 en el 17%, el 41% y el 24% de los pacientes con hipertensión, diabetes y mayores de 60 años, respectivamente. Se encontró una TFGe reducida (<60 ml/min/1,73m2 ) en el 23%, el 12% y el 22% de estos mismos grupos de pacientes. La prevalencia de los marcadores de ERC aumentaba cuanto mayor era el número de factores de riesgo. Conclusión: La elevada prevalencia de marcadores de ERC en una población de riesgo detectada por los médicos de atención primaria en este estudio de colaboración parece ser la mejor forma de motivar a estos especialistas para que realicen cribados de ERC con regularidad (AU)

Lower serum paraoxonase-1 activity is related to linoleic and docosahexanoic fatty acids in type 2 diabetic patients.

BACKGROUND: Serum paraoxonase-1(PON-1) activity is decreased in clinical conditions associated with low high-density lipoprotein cholesterol (HDL-C), increased lipid peroxidation and low-grade chronic inflammation, as in type 2 diabetes mellitus (T2DM). Until now there are no data about the association of any fatty acid (FA) with PON-1 activity in T2DM. METHODS: Twenty patients with T2DM and 16 healthy controls were included in this cross-sectional study. Serum PON-1 activity, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity as well as plasma glucose, HbA1c, lipids, high-sensitivity C-reactive protein (hs-CRP) and insulin resistance, homeostasis model assessment (HOMA-IR) were measured. The preparation of FA methyl esters and their gas chromatography (GC) analysis were also performed. RESULTS: HbA1c, plasma insulin, HOMA-IR and triglycerides were higher in patients with T2DM, whereas HDL-C was lower in those subjects. Levels of pro-oxidative enzyme malondialdehyde (MDA) and hs-CRP were significantly higher, and anti-oxidative enzymes SOD and PON-1 activity were decreased in T2DM patients. N-6 PUFAs were higher in T2DM patients, particularly linoleic acid (LA, 18:2 n-6) and arachidonic acid (AA, 20:4 n-6), whereas n-3 PUFA, docosahexaenoic acid (DHA, 22:6 n-3) was lower in T2DM patients. Using regression analysis, we have shown that only LA and DHA independently predicted PON-1 activity of all participants, particularly in patients with T2DM. CONCLUSIONS: Decreased serum PON-1 activity may, in part, be influenced by higher levels of LA and lower levels of DHA in patients with T2DM. Prospective, randomized studies are necessary to confirm these preliminary findings.

Treatment of lupus nephritis by mycophenolate mofetil.

BACKGROUND/AIMS: Mycophenolate mofetil (MMF) has been increasingly used for the treatment of lupus nephritis (LN). The aim of this study was to examine the efficacy and safety of MMF used with low doses of corticosteroids as maintenance therapy in patients with LN. METHODS: The study covered 35 patients, most of them with proliferative types of LN (5 WHO class III, 26 class IV), while 1 had class V and 3 class VI nephritis. MMF was administered in the dose of 1.5-2 g/24 h and prednisone at 10-20 mg/day. The treatment effects were followed over a 12-month period. RESULTS: After 3 months of therapy significant reduction in proteinuria was achieved (2.1 +/- 2.4 g/24 h vs. 1.0 +/- 1.0 g/24 h, p < 0.01) and maintained to the end of the study. In parallel, a significant rise in serum albumin, a fall of cholesterol and a significant increase in mean glomerular filtration rate were noted. Complete remission was achieved in 16 patients (45.7%), including all patients in class III and V plus 10 patients in class IV. Not a single adverse effect was observed. CONCLUSION: MMF combined with low doses of steroids is an effective and safe treatment for the maintenance of stable remission of LN.

Do components of metabolic syndrome contribute to cardiac autonomic neuropathy in non-diabetic patients?

OBJECTIVE: To evaluate whether autonomic dysfunction exist in patients with metabolic syndrome (MetS) to establish any association with components of MetS. METHODS: From July 2008 to January 2009, 32 outpatients attending the University Clinical Center, Zemun, Belgrade, Serbia, 15 with MetS, 17 with type 2 diabetes mellitus (T2DM), and 15 control subjects were recruited for cross-sectional study among adults. The study was completed at the University Clinical Center, Bezanijska Kosa, and University Clinical Center, Dragisa Misovic, Belgrade, Serbia. Inclusion criteria were the presence of MetS without T2DM, T2DM and healthy controls, matched for age and gender. Exclusion criteria were uncontrolled diabetes (glycosylated hemoglobin [HbA1c] higher than 9%), advanced complications of diabetes (retinopathy, nephropathy, coronary heart disease, or peripheral angiopathy). Besides anthropometric and metabolic parameters cardiovascular autonomic reflex tests, ambulatory ECG monitoring, and blood pressure monitoring for 24 hours was obtained. Power spectral analysis of heart rate variability (HRV) was carried out by Fourier transformation. RESULTS: Mean total power (TP) log-transformed (ln), very low frequency (VLF)ln power, and high frequency (HF)ln power were significantly lower in T2DM patients, when compared with controls, and only HFln power was significantly lower in the MetS group. The average value of low frequency (LF)/HFln ratio was significantly higher in T2DM and MetS, and significantly correlated with glucose level of the last one. CONCLUSION: Disturbed HRV indices were present in patients with MetS before the development of T2DM. With this in mind, improvement of glucose metabolism, as well as early detection of cardiac autonomic dysfunction should be important.

Insulin resistance and chronic inflammation are associated with muscle wasting in end-stage renal disease patients on hemodialysis.

Muscle wasting is independent predictor of mortality in end-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD). We investigated the effect of insulin resistance on lean body mass (LBM), and association between insulin resistance, chronic inflammation, and body composition in these patients. We analyzed cross-sectionally body composition, nutritional status and biochemical parameters in 35 non-diabetic ESRD patients who were on MHD. Bioelectrical impedance analysis was performed to quantify body fat, lean body mass and total body water (FAT (%), FAT (kg), LBM (%), LBM (kg) and TBW(%)). The association between LBM (kg) and gender, FAT (kg), high sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment score (HOMA-IR) was recorded. Multiple linear regression analysis using LBM (kg) as dependent variable showed that FAT (kg) (beta = 0.563, p = 0.05), HOMA-IR (beta = 0.619, p = 0.03), and hs-CRP (beta = 0.488, p = 0.04) were independently associated with LBM in males. In females, only FAT (kg) (beta = 0.648, p = 0.001) significantly predicted LBM. Those variables explained 37% of variance of LBM (kg) in males, and 44% in females. It seems that insulin resistance participates independently in the pathogenesis of muscle wasting in both sexes, particularly in males. The effect of chronic inflammation was not so strong in females, and this point out that regulation of muscle wasting in female patients probably differs from that in males.

Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study.

BACKGROUND/AIMS: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. METHODS: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. RESULTS: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9-8.4) to 1.28 g/day (IQR 0.5-2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13-6.48) to 0.84 (IQR 0.42-2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 +/- 3.46 to 2.16 +/- 2.46, between the first (visits 1-2) and last (vists 4-5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 +/- 31.8 to 65.3 +/- 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. CONCLUSION: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

Effect of n-3 fatty acids on nutritional status and inflammatory markers in haemodialysis patients.

AIMS: Nutrition as an aetiological factor participates a great deal in premature atherosclerosis in haemodialysis (HD) patients. The basic mechanisms of end-stage renal disease and premature atherosclerosis are connected with changes in cell functions at the membrane level. We investigated the red cell membrane fatty acids and the effects of fish oil supplements on nutritional status and inflammatory markers in HD patients. METHODS: We examined 42 HD patients (mean age 55 +/- 8 years). The control group consisted of 16 healthy subjects of similar age and sex to the tested group. HD patients were administered supplements with 2.4 g of n-3 polyunsaturated fatty acids per day for 2 months. Before and after supplementation, we examined plasma lipids, cell membrane erythrocyte phospholipids content, serum albumin, haemoglobin, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). RESULTS: Baseline values in the tested group confirmed the presence of essential fatty acids deficiency. A statistically significant negative correlation between TNF-alpha and eicosapentaenoic acid (EPA) (r = -0.497; P < 0.05) and IL-6 and EPA (r = -468; P = 0.03) was found in HD patients before supplementation. There was a significant increase in docosahexaenoic acids, high density lipoprotein cholesterol, plasma albumin, haemoglobin levels in HD patients after supplementation (P = 0.0001). There was a significant increase in EPA (P = 0.01) after treatment, and there was a significant decrease in inflammatory markers (IL-6 and TNF-alpha, P = 0.0001) after supplementation in the tested group. CONCLUSION: A dietary regime with fish oil could be used in dialysis patients to slow down the development of atherosclerosis and improve nutritional parameters.

[Inflammatory markers, nutritional parameters and polyunsaturated fatty acids in hemodialysis patients].

INTRODUCTION: Malnutrition and inflammation are associated with end-stage renal disease. Inflammation leads to reduced synthesis of albumin, transferin, and other negative acute-phase proteins and increases their catabolic rates. The causes of inflammation are multifactorial, including oxidative modification of plasma proteins, interaction of blood with nonbiocompatible membranes, and other infectious processes. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) powerfully predict death from cardiovascular disease in dialysis patients as well as progression of vascular injury. The aim of our study was to establish a correlation between markers of inflammation and parameters of malnutrition in hemodialysis patients. MATERIAL AND METHODS: We examined 42 hemodialysis patients at the mean age of 55+/-8 with dialysis duration 52.6+/-42. For nutritional assessment subjective global assessment (SGA), anthropometric parameters, bio-electric impedance (BIA), and biochemical nutritional parameters were used. We measured their plasma levels of inflammatory markers: C-reactive protein, IL-6 and TNF-alpha. Patients with severe malnutrition had higher level of IL-6 and TNF-alpha. RESULTS AND DISCUSSION: The following correlations between measured parameters emerged. There was a negative correlations between serum albumin concentration and inflammatory markers (r=-0.31; p=0.05). Anthropometric parameters in hemodialysis patients were lower when inflammatory markers were higher and correlation was significant (p=0.05). A statistically significant negative correlation between TNF-alpha and EPA (r=-0.497; p<0.05) and IL-6 and EPA (r=-468; p=0.03) was found in hemodialysis patients. CONCLUSION: The main findings of this study were that the decrease of nutritional parameters in hemodialysis patients were related to the degree of inflammation. Nutritional factors, as essential fatty acids, could lead to permanent changes in the inflammatory process.

[Predictors of mortality in dialysis patients--association between malnutrition, inflammation and atherosclerosis (MIA syndrome)]. / Prediktori mortaliteta kod bolesnika na dijalizi--povezanost malnutricije, inflamacije i ateroskleroze (mia syndrome).

INTRODUCTION: Numerous recent studies have shown increased comorbidity and mortality in dialysis patients with malnutrition. Protein-energy malnutrition with muscle wasting occurs in a large proportion of patients with chronic renal failure and is, in addition to atherosclerosis, a strong risk factor for mortality in patients undergoing dialysis. Malnutrition is also associated with increased cardiovascular mortality in dialysis patients. PATHOGENIC FACTORS OF MALNUTRITION IN DIALYSIS PATIENTS: Malnutrition is associated with a number of metabolic and vascular abnormalities. These factors include hypoalbuminemia, dyslipidemia with raised triglyceride concentrations, low-density lipoprotein and very low-density lipoprotein concentrations, insulin resistance and high concentrations of acute-phase proteins. Low serum albumin concentration, usually used as an index of malnutrition, is highly associated with increased mortality risk in dialysis patients. However, serum albumin is affected by factors other than malnutrition and high concentrations of acute-phase proteins, such as C-reactive protein (CRP), which correlate with low serum albumin in malnourished patients on dialysis. Oxidative stress has emerged as an important cofactor for development of endothelial dysfunction as premature atherosclerosis. In this context, malnutrition, inflammation and markers of oxidative stress are associated with vascular diseases. ETIOLOGY OF MALNUTRITION IN DIALYSIS PATIENTS: In recent studies several reports have suggested that inflammation, alone or in combination with low protein intake, plays a significant role in etiology of malnutrition in uremic patients. Lipid abnormalities may not only be a consequence of renal disease, but also contribute to its progression. Lipoprotein (a) is also associated with various atherosclerotic diseases. THERAPY OPTIONS: New treatment strategies, such as high protein/energy vs. standard protein/energy nutritional regimens, are necessary as well as food intake and dietary supplements. Intensive supplementation of (1.5 g protein/kg/d and 45 kcal/kg/d) is necessary to improve nutritional status of dialysis patients. CONCLUSION: Cellular basis of pathogenetic factors in malnutrition is unclear. It is, however, now recognized that oxidative stress and inflammatory cytokine aggravates the nutritional status of these patients.