Relationship between asymmetric dimethylarginine [ADMA] and endothelial dysfunction in chronic renal failure patients

The aim of this study was to assess serum asymmetric dimethylarginine [ADMA]and their relation to endothelial dysfunction in chronic renal failure [CRF] patients. A total of 50 CRF patients were divided to 2 groups [25 CRF patients on conservative treatment with glomerular filtration rate [GFR] 41.04 +/- 10.5 ml/min/1.73 m[2], and 25 patients on regular hemodialysis [HD], in addition to 20 healthy controls were studied. GFR was estimated by Cockroft-Gault formula. ADMA was measured by an enzyme- linked immunosorbent assay. Endothelial dysfunction was measured by flow-mediated dilatation [FMD] in brachial artery using high-resolution ultrasound. In addition, C-reactive protein [C-RP], serum albumin, total protein, total cholesterol, low density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], triglyceride and 24-h urinary proteins were performed. Compared with controls, CRF patients on conservative treatment as well as HD patients had higher levels of serum ADMA, brachial artery FMD was significantly lower among CRF patients on conservative treatment and HD patients, suggesting greater endothelial dysfunction, when CRF patients on conservative treatment were compared with HD patients, those HD patients had higher ADMA levels. Moreover, Serum ADMA levels did not change significantly after 4-hour dialysis in HD patients. In multivariate correlation, serum ADMA levels were correlated and independent predictor of FMD. serum ADMA levels were increased in CRF patients on conservative therapy and HD patients, and may be one of the contributing factors for the development of endothelial dysfunction in these patients

Influence of sympathetic activity on the progression of chronic kidney disease

There is clear evidence that chronic kidney disease [CKD] is often characterized by the presence of sympathetic hyperactivity. Data accumulating that this sympathetic hyperactivity is indeed important, because it may influence cardiovascular and renal prognosis. The aim of this study was to assess the relationship between glomerular filtration rate [GFR] and the levels of norepinephrine [NE] in serum and urine in the presence of variable degrees of renal functional impairment. A total of 75 CKD patients were divided into 5 groups according to GFR, group 1: 15 CKD patients with GFR>90ml/min/1.73m2 [stage 1CKD]. group 2: 15 CKD patients with GFR 60-89ml/min/1.73m2 [stage 2 CKD]. group 3: 15 CKD patients with GFR 30-59ml/min/1.73m2 [stage 3 CKD]. group 4: 15 CKD patients with GFR 15-29ml/min/1.73m2[stage 4 CKD]. group 5: 15 CKD patients with GFR<15ml/min/1.73m2 [stage 5, endstage renal failure], in addition to 15 healthy controls were studied. GFR was estimated by Cockroft-Gault formula. Norepinephrine was measured by an enzyme-linked immunosorbent assay. In addition, blood urea, serum creatinine, C-reactive protein [C-RP], fasting blood sugar [PBS], serum total cholesterol, triglycerides and 24-h urinary proteins were performed. Compared with controls, CKD patients had higher levels of serum norepinephrine, urinary norepinephrine was significantly lower among CKD patients. When GFR was reduced in CKD patients, serum norepinephrine was elevated and urinary norepinephrine was reduced suggesting greater renal impairment. In multivariate correlation, GFR were negatively correlated with serum norepinephrine and positively correlated with urinary norepinephrine. Serum norepinephrine levels were increased and urinary norepinephrine excretion were decreased in CKD patients, and may be one of the aggrevating factors for deterioration of renal function in those patients

Relationship between asymmetric dimethylarginine [ADMA], proteinuria and endothelial dysfunction in chronic kidney disease

The aim of this study was to assess serum asymmetric dimethylarginine [ADMA] and their relation to endothelial dysfunction in chronic kidney disease [CKD] Patients with proteinuria. A total of 54 CKD Patients with normal glomerular filtration rate [GFR] were divided into three groups based on their urinary protein excretion in 24 h: 23 patients with nonnephrotic proteinuria [< 3.5 g/d], 17 patients with nephritic-range proteinuria, 14 patients with nephrotic-range proteinuria and secondary amyloidosis [SA] by renal biopsy, in addition to 18 healthy controls. Renal function was estimated with the Cockroft-Gault formula. ADMA was measured by high-performance liquid chromatography [HPLC], assessment of endothelial dysfunction by measuring flow-mediated dilatation [FMD] in brachial artery using high-resolution ultrasound. In addition, high sensitivity C-reactive protein [hsCRP], total cholesterol, triglycerides, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], serum albumin and insulin resistance were performed for all patients. The proteinuric patients had higher levels of serum ADMA. hsCRP and insulin resistance. Compared with controls, brachial artery FMD was significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA levels and lower FMD measurements. Even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. In conclusion, serum ADMA concentrations were increased in CKD, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality

Thyroid functions on hemodialyzed patients

Abnormalities in thyroid function tests are frequently encountered in uremic patients. Disturbance in endothelial dysfunction and inflammatory processes are common in individuals with chronic renal failure. This may predispose to accelerated atherosclerosis with all its complications. The study was performed to investigate relationship between thyroid function and markers of endothelium damage and inflammation in patients with regular hemodialysis [HID]. The study was performed on 50 patients with end stage renal diseases [ESRD] on regular ND for at least 10 months. All patients and control were subjected to complete history and clinical examination and measurements of thyroid function tests, marker of inflammation [CRP], marker of endothelial damage, [intracellular adhesion molecules [ICAM]], in addition to renal function, CBC, lipid profile, total protein and serum albumin. Out of 50 patients under hemodialysis, had cardiovascular events. The following parameters were significantly higher in patients under HD than control; blood urea [p < 0.001], serum creatinine [P <0.001], CRP [p <0.001], ICAM [p <0.001] and triglycerides [P <0.01]. The following parameters were significantly lower in patients under HD than controls; serum albumin [p < 0.001], FT3 [p <0.01, but still within the normal range] and hemoglobin [p < 0.01]. Using multiple regression analysis serum FT3 negatively correlated with, duration of RD [r=-0.830, p < 0.001], albumin [r=-0.770, p <0.001], CRP [r=-0.840, p < 0.001], ICAM [r=-0.500, p < 0.01], triglycerides [r=-0.540, p <0.01], and total protein [r=-0.520, P <0.01]. Logistic regression analysis and after adjusted for age, sex, BMI, hypertension, FT3 levels were independently related to CRP [OR 206, 95% CI 1.6-5.4, P < 0.001], followed by duration of dialysis [OR 2.58, 95% CI 1.7-5.2, P <0.001], lastly serum albumin [OR 2.32, 95% CI 1.6-3.9, p <0.001]. Interestingly, and serum albumin were significantly lower, while CRP and duration of dialysis were significantly higher in patients with vascular complications than the rest of patients [P < 0.01]. We can conclude that thyroid dysfunction in HID patients related to inflammation, duration of dialysis, malnutrition and to a lesser extent endothelial dysfunction. All these factors lead to accelerated atherosclerosis and cardiovascular complications and a clinical significance of these findings merits further studies

Evaluation of serum fetuin-A: relationship with endothelial dysfunction in hemodialyzed patients

The aim of this study was to evaluate the association between serum fetuin-A concentrations and endothelial dysfunction in hemodialyzed [HD] patients. 85 patients on regular HD [55 males and 30 females] and 30 healthy controls [17 males and 13 females] were studied. We measurd serum fetuin-A by enzyme-linked immunosorbent assay. Assessment of endothelial dysfunction by measuring common carotid artery intima media thickness [CCA-IMT] and intima media thickness-inhomogeneity using high-resolution ultrasound. In addition, C-reactive protein [hsCRP], serum calcium, phosphate, intact parathyroid hormone [iPTH], albumin, total cholesterol, triglycerides, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL -C] and fasting blood sugar were performed. Compared with controls, HD patients had a lower levels of serum fetuin - A, higher levels of CRP and 'iPTH, a greater CCA-IMT as well as CCA-IMT-inhomogeneity. Dialysis patients with cardiovascular disease [CVD] had a greater CCA-IMT and IMT-inhomogeneity compared with patients without CVD. IMT-inhomogeneity strongly correlated with IMT. In multiregression analysis, serum fetuin-A correlated with IMT-inhomogeneity but not with IMT, and hsCRP neither correlated with IMT-inhomogeneity nor with IMT. In conclusion, serum fetuin-A concentrations were decreased in HD patients and may be one of the contributing factors for the development of endothelial dysfunction in these patients

Hepcidin level and its relation to ferrokinetic status in chronic renal failure patients on regular hemodialysis

Hepcidin, a key regulator of body iron homeostasis by blocking its intestinal absorption and its release by the reticuloendothelial system. The aim of the study was to assess serum hepcidin levels and its relation to ferrokinetic parameters in hemodialyzed [HD] patients. Fifty five patients on regular HD] [35 patients treated with erythropoietin and 20 patients without erythropoietin therapy] and 20 healthy controls were studied. Hepcidin and C-reactive protein [C-RP] were measured. Ferrokinetic parameters, complete blood count, kidney function, liver functions and lipid profile were assessed. The weekly erythropoietin dose and the patients demographics were recorded. In comparison to the healthy controls, the HD patients had higher serum ferritin, C-RP and hepcidin levels. Erythrocyte count, hemoglobin [Hb], hematocrit [Hct], serum iron, total iron binding capacity [TIBC], transferrin saturation [TSAT], total protein and albumin were low in HD patients. In univariate analysis, hepcidin levels were positively correlated with total protein, albumin, triglyceride, S. creatinine, ferritin and erythropoietin dose, and negatively correlated with age, erythrocyte count, Hb and Hct values. In multiple regression analysis, hepcidin levels were positively correlated with serum calcium, albumin, leukocyte count, triglyceride, serum iron, C-RP and TSAT and negatively correlated with hemoglobin. In conclusion, high serum levels of hepcidin in HD patients may be due to accumulation in the serum, and low grade inflammation my also be contributed. Elevated serum hepcidin levels in HD patients could be responsible, at least in part, for functional iron deficiency and anemia in these patients

Relationship between thyroid function and endothelium dysfunction in hemodialyzed patients

Chronic renal failure affects thyroid function in many ways. Disturbances in hemostasis and inflammation are common complications of kidney diseases. Endothelial dysfunction may link these two processes. The study was performed to assess thyroid hormones in relation to markers of endothelial damage and inflammation in hemodialyzed [HD] patients. Sixty patients on regular HD [40 patients treated with erythropoietin and 20 patients without erythropoietin therapy] and 30 healthy controls were studied. Thyroid hormones, markers of endotherlial damage [Von Willebrand factor [vWF], intracellular adhesion molecule [ICAM], marker of inflammation [high-sensitivity C-reactive protein [hsCRP] and tumor necrosis factor alpha [TNF alpha], hemostatic parameter [tissue plasminogen activator [tPA], kidney function tests, complete blood count, lipid profile, serum iron, serum albumin and total protein, serum calcium and phosphate were measured. The weekly erythropoietin dose and the patient demographics were recorded. Free T[3] were lower in HD patients compared with controls, markers of hemostasis, inflammation and endotherlial dysfunction were significantly higher in HD patients compared with controls. In all hemodialysis patients, free T[3] was independently related to time on dialysis, albumin, serum iron, total protein, triglycerides, total calcium, vWF, tPA and hsCRP. In the HD patients with CRP less than 6 mg/L, free T[3] was related to time on dialysis, total protein and triglycerides. While in HD patients with CRP greater than or equal to 6 mg/L, free T[3] was related to total calcium and hsCRP. Also in multiple regression analysis the predictors of free T[3] were hsCRP and dose of erythropoietin. We describe a novel relation between thyroid hormones and markers of endothelial dysfunction and inflammation in HD patients. Thyroid dysfunction is related to time on dialysis, endothelial damage, and inflammatory state, frequently encountered in uremia could be responsible for accelerated atherosclerosis and development of cardiovascular complications. Therefore, the relations between thyroid axis and endothelium in HD subjects merit additional studies

Evaluation of hepcidin level and its relation to iron status, inflammation and liver function in hemodialyzed patients

Hepcidin, a key regulator of iron metabolism by blocking its intestinal absorption and its release by the reticuloendothelial system, and modulated in response to anemia, hypoxia or inflammation. The aim of the study was to assess hepcidin correlations with markers of iron status, erythropoietin therapy, liver function and markers of inflammation in hemodialyzed [HD] patients. Fifty patients on regular HD [30 patients treated with erythropoietin and 20 patients without erythropoietin therapy] and 20 healthy controls were studied. Hepcidin and C-reactive protein [CRP] were measured. Iron status, complete blood count, liver function and lipid profile were assessed. The weekly erythropoietin dose and the patients demographics were recorded. In comparison to the healthy controls, the HD patients had higher serum ferritin, CRP and hepcidin levels. Serum iron, total iron binding capacity [TIBC], transferrin saturation [TSAT], erythrocyte count, hemoglobin [Hb], hematocrit [Hct], platelet count and albumin were low in HD patients. In the patient group, hepcidin level were positively correlated with leukocyte count, triglyceride, albumin, aspartate aminotransferase, ferritin and erythropoietin dose and negatively correlated with erythrocyte count, Hb and HCt values. In multiple regression analysis, triglyceride [beta value was 0.27, p <0.05] and albumin [beta value was - 0.30, p < 0.05] were correlated with hepcidin in HD patients. In conclusion, high serum levels of hepcidin in HD patients may be due to accumulation in the serum, low - grade inflammation, frequently found in HD patients may also contributed. Elevated hepcidin levels in HD patients could be responsible for functional iron deficiency and anemia and may be considered as a sensitive tool for functional iron deficiency in these patients

Study of selected cytokines [tumour necrosis factor -alpha and interleukin-18] in patients with diabetic nephropathy

The aim of the present study was to investigate tumour necrosis factor- alpha [TNF-alpha] and interleukin-18 [IL-18] levels, their roles in the pathogenesis of diabetic complications especially diabetic nephropathy. Sixty patients with diabetes mellitus [30 with type 1 insulin dependent diabetes mellitus [IDDM] and 30 with type 2 non -insulin dependent diabetes mellitus [NIDDM] patients and 20 healthy controls were studied. Serum TNF-alpha and IL-18 was measured by enzyme linked immunosorbent assay [ELISA] for all subjects. In addition, fasting blood sugar [FBS], 2 h postprandial blood sugar [2h PPBS], glycosylated hemoglobin [Hb[AIC]], urinary albumin levels, triglyceride, total cholesterol, low density lipoprotein cholesterol [LDL-c], and high density lipoprotein cholesterol [HDL-c] were performed for all subjects. Increased serum levels of TNF-alpha and IL - 18 was evident in both IDDM and NIDDM patients as compared to the control group. Similarly, their levels in patients with diabetic nephropathy increased gradually according to the clinical stage of the disease, being highest in macroalbuminuric stage. Correlation analyses showed that serum TNF-alpha and IL-18 concentration were positively correlated with each other and positively with FBS,2h PPBS, Hb[A1C], triglyceride and urinary albumin excretion levels and negative correlation between TNF-alpha and HDL-c were also found in diabetic subjects. In conclusion, high serum levels of TNF-alpha and IL-18 suggested that they might play a role in the pathogenesis of diabetes mellitus [DM] and in the development of nephropathy in diabetic patients whether of type 1 or 2

Serum adiponectin in type 1 diabetic patients with nephropathy

The aim of the study was to elucidate whether serum adiponectin is associated with renal function, low - grade inflammatory markers, metabolic control and insulin resistance in type 1 diabetic patients with and without nephropathy. A total of 95 type 1 diabetic patients were divided into three groups based on their urinary albumin excretion rate [AER]: patients with normal AER had no antihypertensive medication, while patients with microalbuminuria or macroalbuminuria were all treated with an angiotensin converting enzyme [ACE] inhibitor. Renal function was estimated with the Cockroft-Gault formula. Adiponectin was measured by an immunofluorometric assay. In addition, glycosylated hemoglobin [HB[AIC]], estimated glucose disposal rate [GDR], urinary albumin levels, triglyceride, total cholesterol, high density lipoprotein cholesterol [HDL-c] were performed for all patients. Adiponectin concentrations were higher in women than in men. The levels of adiponectin in type 1 diabetic patients with nephropathy increased gradually according to the clinical stage of the disease, being highest in macro album inuric stage. In a univariate analysis, adiponectin was positively associated with serum creatinine, systolic blood pressure, HB[AIC], total cholesterol, HDL-C and negatively with estimated glomerular filtration rate [GFR] and waist to hip ratio [WHR]. In a multiple linear regression analysis including the above variables, estimated GFR, AER and WHR were independently associated with adiponectin levels. In conclusion, serum adiponectin concentrations were increased in type 1 diabetic patients with nephropathy, and levels were further associated with renal insufficiency

Frequency of pulmonary tuberculosis in cirrhotic patients with resistant chest infection

24 cirrhotic patients with resistant chest infection were selected for this study. Full clinical assessment, liver function tests, abdominal ultrasonography, and tuberculin skin test were done for all patients. Also, bacteriological examination of sputum for acid fast bacilli [AFB] by direct stained film and cultured on Lowenstein-Jensen [L-J] medium for mycobacteria PCR to search for mycobacterium tuberculosis complex DNA using primer set for DNA segment of the IS 6110 was performed for all cases. The prevalence of tuberculosis among the 24 patients was 29.2% by one or more employed technique. Direct microscopy alone showed 2 positive cases [8.3%] for AFB, and L-J cultures were positive in 5 cases [20.8%] whereas PCR revealed 5 [20.8%] patients, 2 of them were negative by direct microscopy and L-J culture. The sensitivity and specificity of direct stained film were 40% and 100% respectively. Whereas the sensitivity and specificity of PCR in diagnosing tuberculosis were 100% and 89.5%. There were significant difference between tuberculous and non tuberculous patients as regard prolonged fever and elevated enzymes whereas no significant difference as regard other studied parameters. In pulmonary tuberculosis is not uncommon cause of resistant chest infection in cirrhotic patients and should be considered as an important cause of such resistance. PCR is rapid, sensitive, specific and valuable tool for diagnosing pulmonary tuberculosis especially in immunocompromised patients