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Bolesław Rutkowski

Publications and source records attributed to Bolesław Rutkowski.

At least 37 records · Page 2Linked to original sources

Disturbances of purine nucleotide metabolism in uremia.

The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. It is believed that hyperphosphatemia and metabolic acidosis triggering enhanced reutilization of purine bases are the factors responsible for changes in erythrocyte nucleotide concentration. During the past decade we have performed several studies. A summary of the obtained results is presented. A high-performance liquid chromatography technique was used for the determination of plasma and intraerythrocyte nucleotide concentrations. Labeled adenine and adenosine were used for measuring adenine incorporation. In CRF patients treated conservatively increased concentrations of ATP levels and other nucleotides such as adenosine diphosphate were found. Adenosine monophosphate and hypoxanthine levels were lower than in controls. In hemodialyzed patients both ATP and adenosine monophosphate intraerythrocyte concentrations were higher than in controls. At the same time, adenosine monophosphate and hypoxantine level were comparable with levels in healthy people. The main pattern of nucleotides during hemodialysis remained unchanged, independent from the mode of therapy. The only exception was a decreased level of hypoxantine. Results of a consecutive study have suggested that the increased rate of adenine incorporation into the adenine nucleotide pool could be partially responsible for the increased ATP concentration in uremic erythrocytes. Last but not least, trying to elucidate the pathomechanism of adenine nucleotide disturbances in uremia, we have found that the concentration of N-methyl-2-pyridone-5-carboxamide (2PY), one of the end products of nicotinamide-adenine dinucleotide degradation, were enhanced in CRF patients to values that are potentially toxic. Our findings suggest that 2PY could be a novel uremic toxin. Disturbances of nucleotide metabolism are one of the important components of uremic syndrome.

Adenosine Triphosphate↗

[Epidemiology of kidney diseases in Poland--pilot study (PolNef)].

Systematic increase of dialysis patient number in the world places an enormous responsibility upon the nephrological society in analyzing the epidemiological situation concerning renal diseases. Early diagnosis of renal disease permits treatment of not only the damaging effects of nephropathy on the kidney but also facilitates introduction of therapy that slows progression of complications due to renal insufficiency. Consequences of such strategy may allow for avoidance of terminal renal failure and to a significant degree may slow down for many years the further progression of chronic renal failure and its' impending results. The aim of the initiated pilot study is an attempt to evaluate the epidemiology of renal diseases in Poland on the basis of screening tests performed on a selected patient city in population numbering 60 thousand. In the first stages of the program, questionnaires will be distributed in order to select the patients that will require more detailed diagnostic procedures and nephrological care. Patient identification in the early stages of disease should bring not only better patient quality of life through adequate treatment but also substantial economic benefits, such as decrease in percentage of patients that will progress to terminal renal failure requiring expensive dialysis treatment.

Humans↗

[Can platelets be synthetized from nucleotides?].

In light of the existing knowledge platelets are not able to de novo synthesis of nucleotides. However single report exists about the possession by thrombocytes of the full enzymatic complex, which is essential to such synthesis. An aim of our study was the estimation of the platelets nucleotide pool of patients subjected to immunossuppresion therapy using azathioprine and mycophenolate mofetil, drugs known to block enzymes of de novo synthesis pathways. Fifty-nine patients enrolled to a study were divided to three groups: hemodialysed patients (n = 28), patients after kidney transplantation receiving azathioprine (n = 16) and kidney transplanted patients receiving mycophenolate mofetil (n = 16). Platelets nucleotides concentration was measured using HPLC. In the group of patients after the kidney transplantation receiving AZA concentration of adenine and guanine nucleotides in thrombocytes were statistically lower both with relation to hemodialysed as and with relation to the healthy group. Similarly platelets of patients after the kidney transplant receiving MMF characterized lower adenine and guanine nucleotides concentration comparatively to hemodialyzed patients. One showed also lower ADP, GDP and AMP concentration with relation to of the healthy volunteers. One from possible reasons of the obtainment of above results can be the possession by platelets enzymes, which are vital to de novo nucleotides synthesis.

Adolescent↗

[Problem of HIV-infected patients receiving dialysis].

According to UNAIDS data there are 40 millions of HIV infected people in the world. 7880 people are infected with HIV (official statistics) in Poland. Because of improvement of dialysis accessibility in Poland there is no limitations of qualification for dialysis for HIV infected patients. In this article authors present general information about HIV infection (epidemiology, diagnostic, clinical picture and treatment), post exposure management and prophylaxis in dialysis centers. We present also algorithms of management with patient with acute/chronic renal failure in dependence on result of HIV test.

AIDS-Associated Nephropathy↗

Is there any relationship between lipids and vitamin B levels in persons with elevated risk of atherosclerosis?

BACKGROUND: There is increasing evidence that plasma homocysteine level is an independent risk factor for atherosclerosis. Low levels of serum folates, cobalamin and pyridoxine are associated with increased risk of cardiovascular disease. Most dietary products contain cholesterol as well as methionine, so hyperlipidemia could be associated with a higher level of homocysteine and inversely with lower levels of B vitamins. The aim of this study was to investigate the differences in levels of lipids and vitamins affecting homocysteine metabolism in different groups of patients. MATERIAL/METHODS: We examined 38 healthy persons, 55 patients hospitalised for cardiac surgery, and 62 patients without clinical evidence of atherosclerosis but with one of the atherosclerosis risk factors (hypercholesterolemia, NIDDM or chronic renal insufficiency). The levels of total cholesterol, triglycerides, vitamin B12, folic acid and vitamin B6 index in serum were determined using routine laboratory methods. RESULTS: We found no association between lipids and B vitamins in any examined group. There were significant differences between concentrations of analysed parameters in all groups of patients as compared to controls. CONCLUSIONS: The lack of correlation between the levels of lipid parameters and B vitamins in serum indicates that these may be independent, additional risk factors for atherosclerosis. Higher vitamin B6 deficiency in dialysis patients is probably caused by low intake combined with the increased requirements of uremic patients. Permanent monitoring of B vitamins in serum is necessary in patients with elevated risk of atherosclerosis, as well as long-term education, careful diet planning and supplementation.

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↗

[Hypertensive nephropathy: pathogenesis, diagnosis and treatment].

Chronic hypertension leads to renal damage known as hypertensive nephropathy or hypertensive nephrosclerosis. Presently, this renal pathology seems to be one of the most frequent causes of end-stage renal disease requiring chronic dialysis. Unfortunately there are many problems with clinical diagnosis of hypertensive nephropathy which cause overestimation of its prevalence. Renal biopsy and morphological examination which is the gold standard of diagnosis is rarely performed in such patients. Histological lesions in hypertensive nephropathy are well recognised: myointimal hyperplasia of arterioles, hyaline arteriosclerosis, wrinkling of basement membrane, collapse of the glomerular tuft, glomerulosclerosis and tubulointerstitial involvement. These changes are believed to result from ischaemia and hyperfiltration. Genetic susceptibility and enhanced apoptosis could be involved in this process as well. One could hope that adequate treatment of hypertension according to international standards would allow to reduce the still increasing number of patients with hypertensive nephropathy. Pathogenesis, epidemiology, and clinical management of hypertensive nephropathy are currently discussed in this brief review.

Arterioles↗

[Pathomechanism of hyperlipoproteinemia in chronic renal failure].

Lipid disorders are one of the known metabolic changes associated with chronic renal failure (CRF) [1, 2]. They are present as: hypertriglyceridemia--existed in 60% of CRF patients and hypercholesterolemia observed in 20-30% of people with this syndrome. These disorders, what was shown also in our own studies, are existing in different intensity in patients treated with maintenance haemodialysis [3], peritoneal dialysis [4] and after renal transplantation as well [5]. Mechanism of hypertriglyceridemia, despite over thirty years of studies, is still not finally elucidated. The opinion that it is a result of impaired triglyceride removal (due to decreased activities of both lipoprotein and hepatic lipases) is well documented, however the role of lipogenesis in its development is obscure [6, 7]. The reports concerning this problem contain contradictory data. In our studies performed several years ago we have shown that lipogenesis rate in white adipose tissue of uremic rats is significantly augmented [8, 9, 10] due to activation of free fatty acid synthase. Therefore, recently we paid once again our attention on the activity of this lipogenesis rate limiting enzyme responsible for the long term regulation. We measured its activity, protein abundance and mRNA level in liver and epididymal white adipose tissue of rats with surgically induced renal failure (two-stage subtotal nephrectomy). The results support the thesis that lipogenesis takes a part in a hypertriglyceridemia found in renal failure. There have been observed a significant increase in plasma triglyceride and VLDL concentrations in uremic animals and it was associated with the increase of FAS activity, FAS protein abundance and FAS mRNA. The results were similar in both studied tissues. Moreover, there have been also observed the increased activities of malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. All these enzymes participate in NADPH production, which is a necessary substrate for fatty acid biosynthesis [11, 12, 13]. Concluding, it appears that the rise in plasma triglyceride and VLDL concentrations observed in CRF rats is not only the result of increased liver and white adipose tissue lipogenesis rate. One has to remember, that these date are strictly original and enabling to elucidation further pathogenesis of hyperlipidemia in CRF. In the second set of experiments performed also in rats with experimentally induced CRF we have found that hypercholesterolemia observed in those animals is dependent on the significant activation of cholesterol synthase, induced by increased production of this enzyme (increment of protein abundance and synthase mRNA [14, 15]. Simultaneously, we have performed original studies on the diurnal rhythm of cholesterologenesis, showing that activity of this process is significantly augmented during whole twenty four hours [15]. Summarizing, one have to underline that our observations have important impact to the elucidation of lipid disturbances pathomechanism. Nevertheless further studies are necessary to establish how experimental data are corresponding with human pathology.

Humans↗

[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↗

[Quality of life and therapy in the elderly patients on chronic peritoneal dialysis].

UNLABELLED: In this study quality of life adequacy of treatment was assessed in 32 PD patients over 65 years of age and compared with younger patients on PD (age 40 on average). Quality of life was examined with help of QLQ-C30 questionnaire, negative emotions with use of HADS and own Aggression Scale, life satisfaction on the Cantril's Ladder. Total weekly clearances were used for adequacy assessment as well as nutrition parameters and rate of anaemia and EPO use. Frequency of complications was also compared. Elderly patients were starting dialysis with lower GFR, but in the course of observation neither total clearances nor nutrition parameters and degree of anaemia did not differ between the groups. Elderly used EPO significantly less frequently in comparison to the younger patients. Peritonitis rate was similar and exit site infections were less frequent in elderly population. There was no difference between quality of life and level of negative emotions between the groups. IN CONCLUSION: PD appears to be effective and acceptable method of dialysis for the elderly.

Adult↗

[Lipid disturbances in the nephrotic syndrome].

Disturbances of lipid metabolism are a constant feature of nephrotic syndrome. In patients with NS they compose a significant risk factor of atherosclerosis and progression of renal insufficiency. However, mechanisms leading to these disturbances are still not fully understood. The paper presents summary of hitherto published studies, experimental, as well as clinical trying to elucidate the patomechanism of lipid disturbances in the course of nephrotic syndrome.

Arteriosclerosis↗

Long-term therapy with recombinant human erythropoietin decreases percentage of CD152(+) lymphocytes in primary glomerulonephritis haemodialysis patients.

BACKGROUND: Recombinant human erythropoietin (rHuEpo) may affect the human immune system. The aim of the 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 interleukins (IL) 2, 6, 10, 12 and tumour necrosis factor alpha (TNF alpha) in primary glomerulonephritis chronic haemodialysis (HD) patients before and under rHuEpo treatment. METHODS: Expression of T-cell surface molecules was measured in 14 HD patients ex vivo by flow cytometry of lymphocytes sampled from peripheral blood and in vitro using whole blood cell cultures stimulated either with phytohaemagglutinin (PHA) or with physiological as well as non-physiological doses of rHuEpo. The concentrations of the cytokines were measured in the supernatants from non- or PHA-stimulated cultures using bioassays (IL2, IL6, TNF alpha) or ELISA tests (IL10, IL12). RESULTS: Compared with findings before the start of rHuEpo 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(+)CD152(+) cells. All these effects became apparent after 6 months of rHuEpo treatment. In vitro stimulation of whole blood cultures revealed that the addition of PHA up-regulated the percentage of CD152(+) lymphocytes, while physiological concentrations of rHuEpo decreased the percentage of CD8(+)152(+) T cells. None of the stimuli used affected the percentage of CD8(+) T cells. The pattern of the cytokines shifted toward TH1 phenotype (increase of IL2 and 12 levels) with a decreased level of proinflammatory cytokines (decrease of IL6 and TNFalpha levels). CONCLUSIONS: The observed decrease of CD152(+) lymphocytes together with the decrease of CD8(+) cells may reflect the improved immune response observed in HD patients under rHuEpo treatment.

Abatacept↗

[Renal replacement therapy in the elderly patients in the Gdansk Pomeranian region].

Aging of population is a common phenomenon all over the civilized world. It results in increasing number of aged patients with end-stage renal disease. We analysed patients over 65 years who have been qualified for renal replacement therapy (RRT) since 1997. From that time age was no longer barrier for RRT in Pomerania region. Number of aged patients starting RRT raised systematically and achieved 61 pts in 2000. It was 25% of all starting this therapy in our region. In this period we observed changes in the causes of primary renal diseases: diabetic nephropathy raised from 15 to 27.8%, but hypertensive nephropathy unexpectedly was stable at 5%. Most of elderly patients qualified for RRT lived in town--74.6%. It means that many of them living in rural areas did not have adequate nephrological care and probably some of them have not been qualified for RRT. Late referral in this group is still a great problem. Many patients have never been referred to nephrologist before starting RRT. In majority of those cases no definitive diagnosis of ESRD was established. At present we are aiming at international standards and patients are started on RRT with lower level of serum creatinine than earlier. Increasing number of patients with diabetic nephropathy and in advanced age will require great effort both from nephrological community and health care system.

Aged↗

Benefits and menaces related to the use of statins in patients after renal transplantation.

Hypercholesterolemia in patients after renal transplantation composes a significant risk factor of cardio-vascular disease, it may also worsen graft survival. Statins are the most potent drugs to lower blood cholesterol. They also posses numerous pleiotropic abilities. The paper presents benefits of the use of statins in patients after renal transplantation, as well as the dangers related to the side effects of these drugs. It underlines that adequate use of statins is worth considering in patients after renal transplantation, taking into account not only their ability to lower cholesterol but also their additional properties positively influencing graft survival.

Atorvastatin↗