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Biomedical subjects

Zbigniew Zdrojewski

Publications and source records attributed to Zbigniew Zdrojewski.

16 recordsLinked to original sources
PubMed2007

Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure.

OBJECTIVE: Sympathetic activation may contribute to both cardiovascular morbidity and the progression of chronic kidney disease. The role of the chemoreceptors in determining sympathetic nerve discharge in patients with chronic renal failure (CRF) is unknown. We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in patients with CRF. METHODS: Utilizing a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation on muscle sympathetic nerve activity (MSNA). We compared effects of breathing 100% oxygen for 15 min with effects of breathing room air for 15 min in 12 stable patients with CRF and in 12 control individuals with similar age, gender, blood pressure and body mass index. RESULTS: The baseline MSNA was elevated significantly in the patients with CRF as compared with the control individuals (50 +/- 2 vs 42 +/- 2 bursts/min; P < 0.05). Reductions in systolic blood pressure and pulse pressure in response to the administration of 100% oxygen were significantly different from those observed during administration of room air in patients with CRF. In patients with CRF, MSNA decreased by 29 +/- 7% (P < 0.01) during hyperoxia but did not change during administration of room air (5 +/- 6%; P = NS). By contrast, neither 100% oxygen or room air changed any measures in control individuals. CONCLUSIONS: Tonic activation of excitatory chemoreflex afferents contributes to increased efferent sympathetic activity to muscle circulation and to blood pressure control in patients with CRF. These findings may have important implications for understanding mechanisms underlying the link between CRF and cardiovascular disease.

Administration, Inhalation↗
PubMed2006

Randomized placebo-controlled study on the effects of losartan and carvedilol on albuminuria in renal transplant recipients.

BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg. RESULTS: The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected. CONCLUSION: Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.

Albuminuria↗
PubMed2005

Remarks on surgical strategy in creating vascular access for hemodialysis: 18 years of one center's experience.

The aim of the study is to evaluate surgical methods for creating vascular access for hemodialysis (HD) in patients with chronic renal failure. Over the last 18 years, 1,827 surgical procedures were performed in 722 patients (399 men and 323 women, mean age 43.7 +/- 17 years) in order to provide and maintain permanent vascular access for HD. Among all the surgical procedures, 992 were based on the construction of arteriovenous fistulas (AVF) and 835 were undertaken as secondary reparative surgical procedures. A total of 992 vascular accesses have been performed, including 904 AVF on upper and 14 on lower extremities as well as insertion of 74 permanent catheters. Radiocephalic AVF (RCAVF) was the principal type of AVF (58.8%). While constructing secondary angio-access after using RCAVF on the other extremity, fistulas with usage of brachial vessels were preferred. A total of 228 AVF of this type were created, including 143 brachiocephalic (BCAVF) and 85 brachiobasilic (BBAVF) AVF. Lately, synthetic grafts (arteriovenous graft, AVG) have been used more frequently, in 90 AVF. A brachial straight graft was the main type procedure performed, with polytetrafluoroethylene (95.6%). The patency of the fistulas has been evaluated. Kaplan-Meier survival curves were calculated to determine primary, primary-assisted, and secondary patency. Log-rank analysis was used to determine differences between curves. Primary, primary-assisted, and secondary patency at 12 months and 24 months were calculated. Comparing AVF patency in two patients' age periods (18-65 years, >65 years), it may be concluded that in the elderly group AVG provides better treatment for AVF. Finally, we conclude that a multidisciplinary approach to vascular access strategy offers the best option to achieve good functional AVF. Autogenous arteriovenous access should be regarded as the most suitable type in creating VA. However, individual conditions should be taken into consideration.

Arteriovenous Shunt, Surgical↗
PubMed2005

[Metabolic acidosis after kidney transplantation].

Metabolic acidosis is a common complication in patients after kidney transplantation. It is caused by inability of transplanted kidney to regenerate bicarbonate buffer. Although every type of acidosis may be present in these patients, the most frequent are renal tubular acidosis and uremic acidosis. Both insufficiency of graft and tubular dysfunction can be caused by ischemic damage, episodes of rejection and cyclosporine A--induced nephrotoxicity. Ketoacidosis due to a post-transplant diabetes mellitus and bicarbonate loss in patients after simultaneous pancreas/kidney transplantation are rarely observed. Each type of acidosis is responsible for serious metabolic disturbances that influence graft and patient survival. The proper diagnosis and appropriate treatment with oral supplements are essential.

Acidosis, Renal Tubular↗
PubMed2004

Low-dose dual blockade of the renin-angiotensin system in patients with primary glomerulonephritis.

BACKGROUND: Treatment with agents interfering with the renin-angiotensin system retards the progressive course of proteinuric chronic renal disease. However, because of unwanted effects associated with such therapy, some patients cannot be treated with these drugs at all or may be administered only very small doses. To find an optimal nephroprotective strategy for these patients, we compared antiproteinuric effects of combination therapy with an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor antagonist in very small doses with treatment with either agent alone at greater, but not maximal, doses. We compared the concomitant use of benazepril, 5 mg, and losartan, 25 mg, and monotherapy with these agents in doses 2-fold greater. METHODS: This is a randomized, open, crossover study of 3 treatments in 3 periods of 4 months each. Twenty-four patients with primary glomerulonephritis and nonnephrotic proteinuria, recognized previously as not able to be administered high doses of drugs from these classes, completed the protocol. RESULTS: Combined therapy decreased 24-hour proteinuria (-45.54% versus baseline) more effectively than either losartan (-28.17%; analysis of variance, P < 0.01) or benazepril (-20.19%; analysis of variance, P < 0.001) alone. Subgroup analysis showed that antiproteinuric effects of combination therapy, as well as losartan or benazepril alone, were significantly greater in patients with basal proteinuria greater than 2 g/24 h than in those with proteinuria less than this value (P < 0.001, P < 0.01, and P < 0.05, respectively). All therapies significantly decreased blood pressure (BP) compared with baseline, but there were no differences between treatments in BP changes. CONCLUSION: The study shows that combination therapy with very small doses of losartan and benazepril was more effective in reducing proteinuria than greater doses of either agent in monotherapy, and this greater antiproteinuric efficacy was independent of changes in BP.

Adult↗
PubMed2004

[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↗
PubMed2003

[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↗
PubMed2003

[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↗
PubMed2003

[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↗
PubMed2002

[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↗
PubMed2002

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↗
PubMed2002

[Mechanisms of statin nephroprotective actions].

The great importance of HMGCoA reductase inhibitors (statins) in treatment of hyperlipidemia is well known, and accepted. Numerous multicenter trials have shown the effectiveness of statins in lowering cholesterol concentration, slowing down progression of atherosclerosis, and in decreasing number of cardio-vascular incidents. However, since the discovery of statins experiments have been carried out showing other mechanisms of action of these drugs. Many circumstances expose the antiproliferative, and antiinflammatory influence of HMGCoA reductase inhibitors. This paper presents a review of the studies on these mechanisms with a special emphasis on their nephroprotective role.

Anticholesteremic Agents↗