[The role of aldosterone in cardiovascular alterations in patients with chronic kidney disease].
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Aldosterone↗
Biomedical subjects
Jacek Manitius
Publications and source records attributed to Jacek Manitius.
[Advanced glycation end products (AGEs) and renal failure].
In the last decade a central role has been attributed to advanced glycation end products (AGE's) in the progression of accelerated atherosclerosis and progresion of chronic renal failure, especially in diabetic nephropathy. Deleterious effects of high AGE's concentration was observed mainly in diabetic hemodialyzed patients. D. M. type 2 is the most common cause of renal failure and renal replacement therapy in Poland and in the world. Diabetic complications are of huge medical and social interest. Therefore it is import ant to reveal all the mechanisms responsible for development of diabetic complications especially diabetic nephropatyhy. A significant role is also played by high cardiovascular mortality in hemodialysis patients, which is caused by atherosclerotic changes in vessels.
Animals↗
[Cardiovascular system in patients in different stages of chronic kidney disease].
The term "chronic kidney disease" (CKD) was introduced recently to nephrological literature. CKD is a growing epidemic problem, which affects 11% of adult US population. CKD, particularly with GFR below 60 ml/min/1, 73 m2 is associated with increased risk of cardiovascular morbidity and mortality. It is a result of coexistance of "traditional" cardiovascular risk factors cumulation such as hypertension, lipid and carbohydrate disorders but also "non-traditional" cardiovascular risk factors such as: anemia, calcium-phosphate metabolism disturbances, chronic inflammation and others. The paper discusses changes in left ventricle structure and function, arterial structure and function and cardiovascular calcifications in different stages of chronic kidney disease, and their prognostic significance. Result of the study in 31 CKD patients (GFR 39,4 +/- 14, 1 ml/min/m2) and 18 appearently healthy controls are also presented in the paper. Cardiovascular risk factors assessment, echocardiography, common carotid artery USG with diameter and intima-media thickness (IMT) measurement and aortic pulse wave velocity (PWV) measurement were performed in all participants. We found higher total cholersterol, LDL-cholesterol, triglicerides, CRP, advanced glycation end-products (AGE), and calcium x phosphorus product and lower hemoglobin concentration in CKD patients. Fasting glucose and insulin concentration did not differ between CKD patients and control group but insulin/glucose ratio was higher in CKD group. Abnormal left ventricular heart structure was found in 55% of CKD patients. Carotid artery internal diameter, intima-media thickness and aortic PWV--a marker of increased arterial stiffness - were higher in CKD patients. The study indicates that cardiovascular risk factors and cardiac and arterial abnormalities should be evaluated from the start of CKD.
Adult↗
[Some metabolic and genetic risk factors and the progression of IgA nephropathy--preliminary report].
IgA nephropathy is currently the most frequently occurring type of primary glomerulonephritis. Studies aimed at determining the factors of favorable and unfavorable prognosis in the progression of the disease are conducted. Apart from the above renal disease progression factors, it seems that renal functional reserve (RFR), indirectly indicating the functional status of intrarenal vessels can be a marker assisting in determining prognosis and effectiveness of applied treatment. Decrease in RFR is one of the first symptoms of renal damage, since it precedes decrease in GFR assessed in resting condition. The aim of our study was to assess selected functional (RFR), metabolic, and genetic parameters of renal disease progression in patients with IgA nephropathy, as well as to determine their effect on clinical progression of the disease. Material and methods. The study comprised 30 patients with renal biopsy proven IgA nephropathy, aged 35,2 +/- 8,9, 12 women and 18 men, who had conducted a 12-month period of observation and treatment. The patients' RFR was measured and the following parameters in blood pressure samples were established: creatinine, BUN, uric acid, total cholesterol (TCH), HDL and LDL and TG, homocysteine, endothelium functional indicators: vWF:Ag, TPA:Ag, PAI-1, polymorphism of the human angiotensin converting enzyme gene and endothelial nitric oxide synthase gene. In 24-hour urine collection N-acetylglucosaminidase excretion and daily protein loss were measured. Results. During treatment, changes in some biochemical indicators were observed (uric acid, TCH, LDL, DUB, NAG, erythrocyturia, homocysteine), while others remained stable. Statistically significant differences in concentrations of endothelial antigens: vWF:Ag and PAI-1 were found. Conclusions. Based on the analysis of the results it was concluded that functional status of intrarenal vessels is related to functional status of endothelium and renal tubulae, and also that it probably affects the response to treatment. Decrease of proteinuria during treatment is, among others, related to decrease of metabolic disorders, while the initial results of analysis of polymorphism of the human angiotensin converting enzyme gene and endothelial nitric oxide synthase gene suggest that it may affect the decrease of proteinuria and concentration of homocysteine in the blood.
Adult↗
[Endothelial dysfunction in peritoneal dialysis patients and its relationship to nutrition].
Endothelial dysfunction (ED) in peritoneal dialysis patients plays pivotal role in progression of atherosclerosis and hemostasis disturbances. Malnutrition is one of the most important complication of PD. Both ED and malnutrition cause higher rate of cardiovascular events in these patients. 32 PD patients were analyzed. Endothelial function was assessed by measurements of serum level of vWF:Ag; t-Pa:Ag; TM:Ag. Nutritional status assessment included: body mass index-BMI, MAMC measurements; and serum albumin, total protein, prealbumin, transferrin, cholesterol, insulin, insulin like growth factor-1 (IGF-1). There were higher levels of vWF:Ag but lower of t-PA:Ag and TM:Ag after 12 month of observation. Serum levels of prealbumin, insulin, cholesterol were stable, but there were lower levels of albumin, IGF-1, and higher of transferrin at the end of the follow up. There were no differences in anthropometric indices during the follow up. We found statistically significant linear correlations: t-Pa:Ag vs prealbumin; t-Pa:Ag vs cholesterol; TM:Ag vs albumin. In the course of 12 months observation of peritoneal dialysis patients we found deterioration of endothelial function, expressed by evaluated endothelial antigens. Some correlations found in our study might express close relationship between endothelial function markers and nutritional status.
Adult↗
Cardiac valve calcifications and left ventricular hypertrophy in hemodialysis patients.
Cardiac valve calcification (VC) is a common finding in end-stage renal disease patients. It was shown recently that VC is an independent predictor for all-cause and cardiovascular mortality in peritoneal dialysis patients. In hemodialysis (HD) patients, VC was associated with all-cause and cardiovascular mortality, but after adjusting for other cardiovascular risk factors and complications, as well as left ventricular mass index (LVMI), it lost significance. The aim of the study was to assess the relationship between VC and left ventricular hypertrophy in hemodialysis patients. Echocardiographic examination with mitral and aortic valves assessment and LVMI calculation was performed in 65 HD patients ages 49+/-12, with duration of HD therapy 38+/-32 months. VC were found in 32 of 65 patients (49%)-Group VC(+), mitral valve calcifications (MVC) in 10, aortic valve calcifications (AVC) in 9, and both valves calcifications (MVC+AVC) in 13 patients. Patients with VC were older, on HD therapy were longer, had higher systolic and pulse pressure, and had higher LVMI. Patients with both VCs had the highest LVMI. No significant differences were found with respect to Ca, P, PTH, and mean Ca x P product, but the incidence of Ca x P product above 4.43 mmol2/L2 was higher in VC(+) compared with those without VCs. VC coexists with left ventricular hypertrophy, particularly when both valves are calcified. Even short-lasting incidents of increased Ca x P product may lead to cardiac VC.
Adult↗
Interpretation of erythropoietin levels in patients with various degrees of renal anemia.
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Biomarkers↗
[Predictors of successful renal artery revascularization in atherosclerotic renovascular disease].
Atherosclerotic renovascular disease (ARVD) is defined as a reduction in glomerular filtration rate in patient with significant renovascular bilateral occlusive disease or unilateral in a solitary kidney. ARVD is a frequent and potentially avoidable cause of end stage renal failure and the need for replacement therapy among person above 50 years old. Use of balloon angioplasty with stenting or surgical repair has been shown to improve renal potency, but there is no clear evidence that it prevents further progressive decline of renal function or blood pressure, compared to medical therapy alone. It is now recognized that severity of histopathologic damage is an important determinant and predictor of renal functional outcome. Proteinuria increases with declining renal failure and reflects the severity of parenchymal damage. Proteinuria and high renal resistance index are associated with glomerular damage and altered intrarenal perfusion. They aren't linked to renal artery stenosis (RAS) grade. Recent study indicate that abrupt decline in renal function reflects reversibility after revascularization. This should probably be undertaken in RAS patients with rapidly deteriorating renal function, refractory hypertension and in whom plasma creatinine concentration has increased by >20% during one month long administration of angiotensin-converting enzyme inhibitor. Renal biopsy may be useful to evaluate patient who will have advantage from revascularization.
Angioplasty, Balloon↗
[HIV-associated nephropathy. Case report].
The clinical case described below forces us to ask two basic questions: whether the patient is suffering from two separate, co-existing illnesses, i.e. primary nephritic syndrome or the nephritic syndrome in connection with Schoenlein-Henoch disease, with accompanies the HIV infection, or nephropathy, development of which has been triggered by HIV infection.
AIDS-Associated Nephropathy↗
Effect of parathormone on heart rate variability in hemodialysis patients.
INTRODUCTION: Parathormone (PTH) is a very potent uraemic toxin, which affects heart structure and function. PTH also plays the role in uraemic autonomic neuropathy (AN). The aim of the study was to investigate the relationship between high PTH level and AN assessed with frequency domain measures of heart rate variability (HRV). MATERIALS AND METHODS: A 24-h ECG was performed in 40 HD (F=19, M=21) patients aged 49+/-11 years, duration of HD therapy 37+/-30 months. Frequency domain measures of HRV were obtained according to European Society of Cardiology recommendations. Total spectral power (TP), high frequency band (HF) and low frequency band (LF) were computed as indexes of: total autonomic nervous system (ANS) activity, parasympathetic and sympathetic activities, respectively. LF/HF ratio was calculated. TP, HF, LF and LF/HF were expressed as natural logarithm. Patients were divided into two groups due to PTH level: PTH+ (PTH> or =275 pg/ml) and PTH- (PTH<275 pg/ml). RESULTS: The values of lnTP and lnLF were lower in patients PTH+ than in patients PTH- (6,58+/-0,76 vs. 6,99+/-0,44 ms2, p<0,05, and 4,91+/-0,99 vs. 5,33+/-0,65 ms2, respectively, p=0,06). We also found negative correlation between lnPTH and lnTP (r=-0,47; p<0,005), lnPTH and lnLF (r=-0,35; p<0,05), lnPTH and lnHF (r=-0,34; p<0,05). On multiple regression analysis, lnTP, lnLF and lnHF were independently related to lnPTH. CONCLUSIONS: Parathormone exerts effect on activity of both parts of autonomic nervous system: sympathetic and parasympathetic. High PTH level deteriorates total autonomic activity.
Adult↗
Effect of 12-month therapy with omega-3 polyunsaturated acids on glomerular filtration response to dopamine in IgA nephropathy.
BACKGROUND: Omega-3 polyunsaturated acids therapy is efficient in primary IgA nephropathy. It is unknown whether doses of omega-3 smaller than those given previously are still effective. The aim of the study was to examine the effect of omega-3 therapy on renal vascular function in relation to proteinuria and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). METHODS: 20 IgA patients aged 36.5 +/- 10.77 with creatinine clearance (Cr(cl)) 105.71 +/- 27.3 ml/min and proteinuria 3.31 +/- 2.01 g/24 h were given orally 810 mg EPA and 540 mg DHA daily for 12 months. Before and at the end of the study, 24-hour proteinuria, serum homocysteine, and Cr(cl) were measured. At the same time, renal vascular function was estimated as dopamine-induced glomerular filtration response (DIR). DIR was measured as: two 120-min lasting Cr(cl) (before and during 2 microg/kg b.w./min i.v. dopamine). RESULTS: The results obtained during follow-up were as follows (baseline vs. after therapy): DIR 14.9 +/- 16.4 vs. 30.3 +/- 14.3% (p < 0.01); urine protein 2.31 +/- 2.01 vs. 1.31 +/- 1.37 g/24 h (p < 0.01); (Cr(cl)) 105.71 +/- 27.3 vs. 103.9 +/- 20.9 ml/min (n.s.); NAG 8.3 +/- 1.8 vs. 6.0 +/- 1.2 U/g(creat) (p < 0.01), and homocysteine 16.2 +/- 3.15 vs. 13.8 +/- 2.6 micromol/l (p < 0.05). The only correlation found was linear correlation between basal DIR and DIR change (r = -0.570; p < 0.010) and basal NAG (r = -0.460; p < 0.50). CONCLUSIONS: Omega-3 supplementation is associated with the improvement of both renal vascular function and tubule function.
Adolescent↗
Selenium and glutathione peroxidases in blood of patients with different stages of chronic renal failure.
In patients with chronic renal failure (CRF) Se concentration in blood components is usually lower as compared with healthy controls. One of the five known forms of Se-dependent glutathione peroxidases (GSH-Px), the plasma GSH-Px, is synthesized primarily in the kidney. In CRF patients, plasma GSH-Px activity is reduced and the reduction increases with the progress of the disease. The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as complexing reagent. Activities of GSH-Px in red cells and in plasma were assayed by the coupled method with t-butyl hydroperoxide as substrate. The study group consisted of 150 patients in different stages of CRF. The results were compared with the values for 30 healthy subjects. Se concentrations in whole blood and plasma of the entire group of patients were significantly lower (p < 0.01) as compared with the healthy subjects. In the incipient stage, however, the Se levels in all blood components were non-significantly lower. In whole blood and plasma the Se levels gradually decreased, reaching in the end stage values that were lower by 29 to 32% (p < 0.0001) as compared with the control group. Total protein and albumin levels in plasma of patients were significantly lower (p < 0.0001) as compared with healthy subjects and they decreased linearly with the progress of the disease. Positive and highly significant correlations were noted between total plasma protein and plasma Se concentrations (p < 0.0001) as well as between plasma albumin and plasma Se concentrations (p < 0.0001). Red cell GSH-Px activity in the entire group of patients was lower (p < 0.05) than in the control group and did not change significantly with the progress of the disease. In plasma, however, GSH-Px activity of the entire group was lower by 33% (p < 0.0001) as compared with healthy subjects and decreased gradually with increasing renal failure. Highly significant, inverse correlations were seen between creatinine levels and plasma GSH-Px activities (p < 0.0001) as well as between urea nitrogen levels and plasma GSH-Px activities (p < 0.0001) when all stages of the disease were included. In conclusion, patients with CRF exhibit lower Se levels in blood components as compared with healthy subjects. In whole blood and plasma these levels decrease with the progress of the disease. Plasma GSH-Px activity in patients was extremely reduced and it dramatically decreased with the progress of the illness.
Adolescent↗
The role of intrinsic fibrinolytic system activation in pathogenesis of hemostasis disturbances in hemodialyzed patients with chronic renal failure.
In the hemodialysis patient, hemostasis changes may occur. The contribution of fibrinolysis in pathogenesis of these disorders is unclear. The aim of the study was to estimate intrinsic fibrinolysis pathway in patients treated with hemodialysis (HD) because of chronic renal failure caused by chronic glomerulonephritis. The study was performed with 43 patients; the control group consisted of 51 healthy volunteers chosen by sex and age. The following parameters were determined: concentration of the urokinase plasminogen activator antigen (uPA:Ag), plasmin--antiplasmin complexes (PAP), fibrin and fibrinogen degradation products (FDP), activity of prekallikrein (PK) and C1-inhibitor (C1-INH) and also euglobulin clot lysis time (ELT). The above parameters were assessed in the patients before and after HD and were compared with the control group. In the HD patients, in comparison with the control group, prolonged statistically ELT [153 (125;215) vs. 105 (75;142) min.; p<0.001], with increase of PAP (508.6 +/- 274.7 vs. 184.7 +/- 69.4 microg/L; p<0.001) and FDP concentrations [5 (5;15) vs. 2.5 (0;0.3) microg/mL; p<0.05] before the procedure were determined. It suggests increased plasmin production and fibrin digestion despite determination of decreased general fibrinolytic activity. The C1-INH activity before HD was also significantly increased as compared with the control group [157 (136;171) vs. 107 (100;124)%; p<0.001], and its significant decreased after the HD is 157.7 +/- 23.9 vs. 122.3 +/- 20.3%; p<0.001, as it seems to be a nondirect proof of intrinsic pathway contribution in fibrinolysis activation in the HD patients. The remaining examined parameters did not change significantly after the dialysis procedure.
Adult↗
The influence of intravenous 1,25(OH)2D3 therapy on glucose metabolism in hemodialyzed patients with secondary hyperparathyroidism.
Glucose intolerance, insulin resistance and hyperinsulinemia are common findings in end-stage renal disease patients. Parathormone (PTH) and vitamin D3 are linked with disturbances of glucose metabolism. Glycated hemoglobin (HbA1c) reflects long-term glycemic control. HbA1c is a marker of increased risk of death in diabetic patients but also in general population. The aim of the study was to investigate the influence of 1,25(OH)2D3 therapy on long-term control of glycemia in hemodialyzed (HD) patients with severe secondary hyperparathyroidism (SHP). Eight HD patients with SHP (PTH=1088.6+/-472.2) were given intravenous 1,25(OH)2D3 1-2 microg thrice a week, for 12 weeks (mean dose 4.5 microg/week). At baseline and after 12 weeks fasting blood was sampled for: glucose, insulin, HbA1c, PTH. Insulin/glucose ratio (I/G) was calculated as marker of insulin resistance. Results were compared with 14 healthy volunteers (controls) matched for age, sex and BMI. At baseline I/G was higher in HD vs controls 0.110+/-0.045 vs 0.073+/-0.021 (p = 0.02), and of borderline significance at follow-up (0.106+/-0.053, p=0.05 vs controls). PTH decreased significantly to 506.1+/-646.3 (p<0.02) during therapy. Significant decrease of HbA1c in HD patients was observed (5.84+/-0.40 vs 5.13+/-0.51; p=0.01), while fasting glucose, insulin and I/G did not change significantly. Intravenous 1,25(OH)2D3 therapy is successful, even in patients with severe secondary hyperparathyroidism. Significant decrease in HbA1c with stable insulin concentration may indicate positive impact of intravenous 1,25(OH)2D3 therapy on long-term glucose metabolism.
Adult↗
Selenium supplementation on plasma glutathione peroxidase activity in patients with end-stage chronic renal failure.
Patients with chronic renal failure (CRF) usually have a lower than healthy level of selenium (Se) in whole blood and plasma. Plasma glutathione peroxidase (GSH-Px) is synthesized mostly in the kidney. In CRF patients, activity of this enzyme is significantly reduced and its reduction increases with the progress of the disease. The aim of the study was to evaluate the effect of Se supplementation to CRF patients at various stages of the disease on Se concentration in blood components and on plasma GSHPx activity. The study group comprised 53 CRF patients at various stages of the disease supplemented with Se (200 microg/d for 3 mo as Se-enriched yeast, containing about 70% L-selenomethionine [SeMet]). The control group consisted of 20 healthy subjects. The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as a complexing reagent. GSH-Px activity in red cell hemolysates and plasma was assayed by the coupled method with tert-butyl hydroperoxide as a substrate. The Se concentration in whole blood and plasma of CRF patients is significantly lower as compared with healthy subjects, but similar at all stages of the disease. In the patients' plasma, total protein and albumin levels are also significantly lower than in healthy subjects. Plasma GSH-Px activity in patients is extremely low, and contrary to Se concentration, it decreases linearly with the increasing stage of the illness. Se-supplied patients show an increased Se concentration in all blood components and at all disease stages, whereas plasma GSH-Px activity is enhanced only at the incipient stage of the disease. Se supply has no effect on plasma GSHPx activity in uremic patients at the end stage of the disease. Total plasma protein and albumin levels did not change after Se supplementation. Our data seem to show that in patients with CRF lower total protein and albumin levels in plasma may be the chief cause of the low blood and plasma Se concentrations. GSH-Px activity decreases along with the kidney impairment. At the end stage of the disease, Se supplementation in the form of Se-enriched yeast has no effect on the increase in plasma GSH-Px activity.
Adult↗
Tubular injury: the first symptom of hypertensive kidney involvement?
BACKGROUND: Tubular injury is an important component of hypertensive nephropathy, but its pathogenesis is not completely clear. We attempted to determine whether tubular injury precedes glomerular involvement, and to evaluate the role of vascular damage and metabolic disturbances in this process. MATERIAL/METHODS: 25 patients with newly diagnosed primary non-treated hypertension without microalbuminuria were studied. 15 healthy volunteers served as controls. We measured total urine activity of N-acetyl-beta-D-glucosaminidase (NAG) as a marker of tubular injury, albumin excretion, serum concentrations of insulin, uric acid and lipids. Intravenous glucose tolerance tests and oral fructose loading tests were performed to assess carbohydrate and purine metabolism. The plasma glucose area (PGA) under the curve of glucose levels obtained from the former test was calculated, as well as the plasma uric acid area (PUAA) under the curve of uric acid levels from the latter. Hypertensive vascular injury was investigated by direct ophthalmoscopy. RESULTS: Significantly higher NAG activity was found in hypertensives in comparison with healthy controls. NAG activity was not influenced by the extent of ophthalmoscopically detectable vascular injury. We found positive correlation between urine NAG activity and PGA. A borderline significant association was also found between NAG activity and PUAA in hypertensive patients. CONCLUSIONS: Our results suggest that tubular injury is present in the early stages of hypertensive nephropathy and may precede glomerular damage. Ischemia due to changes in small vessels may not be the only factor responsible for this injury. Metabolic disturbances, especially carbohydrate abnormalities, may also play a role.
Acetylglucosaminidase↗
[Torasemide (Trifas) in clinical practice--own experience].
Torasemide (Trifas, Berlin Chemie/Menarini) is a loop diuretic and its site of action in the nephron is the afferent section of Henle's loop. Associated with this is its increased effectiveness and reduction of side effects in comparison with other loop diuretics like furosemide. Torasemide acts proportionately to the administered dose, which allows to asses its diuretic effect. It has been used in our Clinic in patients not responding to previous diuretic treatment. The diuretic effect of torasemide has been satisfactory, with no side effects. However, the trial group has not been numerous and was non-homogeneous in regard to renal failure and other disorders.
Acute Kidney Injury↗
[Influence of erythropoietin on immunological system of patients with chronic renal failure].
UNLABELLED: Recombinant human erythropoietin (epoetin) administration is a well established therapy of anaemia in maintenance hemodialysis (HD) patients. During the treatment, along with an increase in haemoglobin (Hb) level also an improvement of physical and sexual activity and cognitive functions was observed. Moreover, recent studies have shown an impact of epoetin on lipid-carbohydrate and protein metabolism, endocrinological functions and immune system [1-7]. It is still unclear whether all these changes are caused by direct epoetin activity or they are associated with the correction of anaemia and better oxygen supply and therefore an improvement of the conditions required for many metabolic function. The goal of the first study performed in our centre was to estimate the influence of epoetin alpha (Eprex) administered in the doses not affecting erythropoiesis (7-10 IU/kg/three times a week for 12 weeks) on serum levels of interleukin (IL) 2, 6 and tumor necrosis factor TNF-alpha [8, 9]. 10 HD patients (3 F, 7 M) aged from 33 to 62 years participated in that study. The level of IL-2, IL-6 and TNF-alpha was measured by means of bioassay using a highly sensitive cell line respectively CTLL, B9 and fibrosarcoma--WEHI 164 (clone 13). Cells viability was tested by colorimetric MTT assay. During the first period of observation stable Hb concentration and unchanged although significantly higher than in healthy people levels of TNF-alpha and IL-6 were noticed. Serum level of IL-2 increased significantly and in the 10 week it reached the values observed in healthy humans although after that period of time it dropped to the initial values. The aim of the following study was to estimate the influence of epoetin on IL-2, IL-10 and TNF-alpha production by whole blood cell culture [1, 2]. 10 HD patients (2 F, 8 M) aged from 35 to 53 years receiving standard doses of epoetin alpha (Eprex) for six months (in vivo experiments) and another 10 HD patients (3 F, 7 M) aged from 40 to 60 years not receiving epoetin participated in the study (in vitro experiments--cell culture were stimulated with different doses of (epoetin alpha--Eprex and epoetin beta--Recormon): 0.05; 0.1; 0.5; 1.0 IU/ml). IL 2 and TNF-alpha were measured using the bioassay mentioned above, IL 10 by ELISA immunoassay. The levels of IL10 increased in all epoetin treated patients and it was accompanied by transitory decrease of TNF-alpha. The levels of IL-2 increased in 7/10 patients under the study. Addition of epoetin in vitro to the whole blood culture of HD patients before implementation of epoetin confirmed that it is able to directly stimulate IL-2 production. The highest levels of stimulation of IL-2 secretion were observed for the physiological doses of epoetin (0.05 IU/ml). The aim of the more recent study was to examine changes in CD4+ and CD8+ T-cell subpopulations, the expression of the inhibitory molecule, CD152+ on T lymphocytes and the levels of IL-2, IL-6, IL-10, IL-12 and TNF-alpha in HD patients [10]. Additionally serum levels of C reactive protein (CRP), C3, C4 components of complement and immunoglobulin IgG, IgM and IgA were measured. 14 patients (8 F, 6 M) aged from 31 to 64 years receiving standard doses of epoetin alpha (Eprex) for twelve months (in vivo experiments) and another 4 HD patients (2 F, 2 M) aged from 43 to 57 years not receiving epoetin participated in the study (in vitro experiments--cell culture were stimulated with epoetin as in previous study). METHODS: IL-2, IL-6, and TNF-alpha were measured using bioassays described above, IL-12 and IL-10 by ELISA immunoassay. Expression of T-cell surface molecules was measured both in vivo by flow cytometry of lymphocytes sampled from peripheral blood and in vitro using whole blood cell culture stimulated with physiological as well as non-physiological doses of epoetin. The levels of C3, C4, IgG, IgM and IgA were estimated using nephelometric method. Compared with the findings before the start of epoetin therapy the CD4+/CD8+ ratio increased after 1 year of follow-up, whereas the percentage of CD152+ peripheral blood lymphocytes decreased. The increase of the CD4+/CD8+ ratio was dependent on a decrease of the percentage of CD8+ cells. The decrease of CD152+ population affected mainly CD8+152+ T cells. All these effects became apparent after 6 months of epoetin treatment. In vitro stimulation of whole blood cultures revealed that the addition of physiological concentration of epoetin decreased the percentage of CD8+152+ T cells. The pattern of the cytokines shifted towards Th1 phenotype (increase of IL-2 and IL-12) with a decreased level of proinflammatory cytokines (decrease of IL-6 and TNF-alpha). Treatment with epoetin did not alter plasma CRP, C3, C4 components of complement, immunoglobulin, as well as total count of lymphocytes. Summing up, administration of epoetin to maintenance HD patients not only treats the anaemia but also results in favourable changes in immune system. Epoetin is probably not only hemopoietic factor but also an immunomodulatory cytokine.
Antigens, CD↗