Jacek Furmaga

Polymorphism of the renalase gene in end-stage renal disease patients affected by hypertension

BACKGROUND Renalase is a novel flavin adenine dinucleotide-dependent amine oxidase that is secreted by the kidney. It circulates in the blood and modulates the cardiac function and systemic blood pressure. Insufficiency of renalase in patients with chronic kidney disease may explain the frequent occurrence of hypertension among patients with end-stage renal disease (ESRD) and an increased risk of cardiovascular events in this group. The aim of the study was to assess the relationship of two renalase gene polymorphisms with hypertension in dialysed patients. METHODS Rs2576178 polymorphism was genotyped in 369 patients, rs10887800 polymorphism was genotyped in 421 dialysed patients, using polymerase chain reaction (PCR) and subsequent cleavage with Msp I and Pst I restriction endonucleases. RESULTS Genotype distribution and allele frequencies of rs2576178 polymorphism were compared in the following subgroups of patients: dialysed patients with hypertension: ESRD HY + (n = 200) and dialysed patients without hypertension: ESRD HY - (n = 169). There was a significant difference in the frequency of the G allele carriers. G allele carriers were associated with a 1.55 times higher risk of hypertension [odds ratio (OR) = 1.55; 95% confidence interval (CI): 1.023-2.357, P = 0.039]. Distribution of genotypes and frequencies of alleles of rs10887800 polymorphism were compared in the following subgroups of patients: ESRD HY + (n = 278) and ESRD HY - (n = 143). The G allele carriers were recognized with a significantly higher frequency in ESRD HY + patients (0.46 in ESRD HY + versus 0.37 in ESRD HY - ) [OR = 1.76; 95% CI: (1.159-2.667, P = 0.008)]. CONCLUSIONS Our results are the first to suggest an association between renalase gene polymorphisms analysed and hypertension in dialysed patients. It may be an important step towards gaining a deeper insight into cardiovascular pathophysiology. Furthermore, it might provide an optimal treatment and better prognosis for patients with chronic kidney disease.

Takotsubo syndrome in a patient after renal transplantation

Summary Background Takotsubo syndrome (TTS) is a transient cardiomyopathy of unknown origin, clinically manifesting as acute coronary syndrome (ACS). This syndrome mainly occurs in postmenopausal women and has a temporary relationship with emotional or physical stress. Case Report TTS occurred in 46-year-old female patient on the first day after renal transplantation. The predominant symptoms were connected with ACS, performed with low grade troponin elevation and characteristic shape of left ventricle depicted in echocardiography. Taking into consideration the risk of the development of contrast-induced nephropathy, coronary angiography (CA) was delayed; myocardial perfusion scintigraphy and iodine-123 metaiodobenzylguanidine (123I-mIBG) myocardial uptake were performed to confirm the clinical suspicion. Myocardial perfusion scintigraphy (MPS) performed in rest condition showed normal perfusion but myocardial uptake of 123I-mIBG was impaired. Within 6 months after surgery, full recovery of all biochemical and functional parameters of the left ventricle were observed. At that time CA was done, depicting normal coronary arteries. Conclusions TTS could be diagnosed by the use of non-nephrotoxic tests – 123I-mIBG myocardial scintigraphy, MPS and echocardiography.

Aortic Stiffness, Left Ventricle Hypertrophy, and Homogeneity of Ventricle Repolarization in Adult Dialyzed Patients

Aim. Study was designed to assess relationship between aortic compliance and homogeneity of heart electrical activity in dialysis patients. Methods. Study group was consisted of 120 dialyzed patients; 57 (age 50,7 ± 7,1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51,6 ± 7,6) were hemodialyzed (HD). Three-dimensional vectorocardiographic (VCG) monitoring was done to assess: QRS-T angle, T el and T az. Echocardiography was performed to assess: Aomax, Aomin, ASI (aortic siffness index). Results. ASI in HD as well as in CAPD patients was significantly higher compared to controls [resp., 5,51 (±1,32), 5,83 (±1,41), 3,07 (±1,09)]. Cut-off value of ASI was 5,67. In HD patients strong correlations between ASI and QRS-T angle, T el and T az were determined (resp., r = 0,429, P < 0,001; r = 0,432, P ≤ 0,001 and r = 0,387, P = 0,001). In CAPD group were significant association between ASI and QRS-T angle, T el and T az (resp., r = 0,452, P < 0,001; r = 0,417, P < 0,001 and r = 0,390, P = 0,001). ASI was independently and markedly associated with: QRS-T angle, T elev, T az, ADMA, cTnT, CRP, Total-chol, LDL-chol in HD and CAPD patients. Conclusions. ASI and VCG indices are higher in HD and CAPD patients. Correlation between ASI and VCG parameters may reflect unfavourable influence of poor aortic compliance on the electrical activity of the heart in dialyzed patients. Hypertrophy aggravates repolarization disturbances in hemodialyzed patients.

The effect of a single dialysis session on spatial QRS-T angle in haemodialysis patients

BACKGROUND Abnormal values of the spatial angle between the directions of ventricular depolarization and repolarization (QRS-T) reflect the action potential inhomogeneities and predict cardiac events and mortality in various patient groups. The study was designed to (i) compare QRS-T in haemodialysis (HD) patients and healthy subjects, (ii) assess the influence of HD on QRS-T and (iii) evaluate the possible associations between QRS-T and echocardiography, haemodynamic as well as biochemical parameters. METHODS The angular differences between the maximum spatial QRS and T vectors were measured in 73 HD patients and in 57 controls. QRS-T in patients was estimated pre- and post-dialysis together with the evaluation of blood chemistry and haemodynamic parameters. RESULTS Pre-dialysis QRS-T was higher compared with controls (30.18 ± 9.84 and 13.65 ± 7.23, respectively; P < 0.001). HD induced an increase of QRS-T (41.09 ± 11.74; P < 0.001). Pre-dialysis QRS-T adjusted for left ventricular mass index correlated with troponin T (r = 0.398, P = 0.001) and HDL (r = -0.270, P = 0.043). The differences between pre- and post-dialysis (Δ) QRS-T correlated with Δ potassium (r = 0.453, P < 0.001), Δ calcium (r = -0.309, P = 0.011) and Δ stroke index (SI; r = 0.311, P = 0.017). On multivariate analysis, troponin T was found to be an independent predictor of pre-dialysis QRS-T, whereas independent predictors of the HD-induced increase in QRS-T were potassium and cardiac index changes. CONCLUSIONS QRS-T is high in HD patients. HD enhances the inhomogeneities of action potential. Pre-dialysis QRS-T is mainly associated with troponin T elevation. HD-induced increase in QRS-T is mainly associated with potassium and SI changes. The possible clinical importance of the higher QRS-T in HD patients remains to be confirmed in further studies.

Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients

This study was performed to investigate the relationship between left atrium (LA) volume index (LAVI) and left ventricle electrical activity presumably repolarization in end‐stage renal disease patients. Study group was consisted of 120 dialyzed patients divided into two subgroups: 57 (age 50.7 ± 7.1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 ± 7.6) were hemodialyzed (HD). All patients were undergoing three‐dimensional vectorcardiographic (VCG) monitoring to assess parameters concerning T vector: QRS‐T angle, Tel, and Taz. Standard echocardiography was performed to assess: LAmax, LAshort, LAlong. LAVI was calculated due to formula: LAVI = (π/6X [LAmax × LAshort × LAlong])/m2. LAVI in HD as well as in CAPD patients was significantly higher compared with controls (respectively: 36.29 ± 10.92; 36.41 ± 11.06; 20.64 ± 6.77 mL/m2). The calculated cutoff value of LAVI was 36.32 mL/m2. In HD patients, the strong correlations between LAVI and QRS‐T angle and Tel were determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006). Similarly in CAPD group were significant associations between LAVI and QRS‐T angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The QRS‐T angle, Tel and Taz are independently and markedly associated with LAVI in both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD patients. Correlation between QRS‐T angle and LAVI may reflect unfavorable influence on the electrical activity of the heart in dialyzed patients with left ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for stratification of ventricle repolarization disturbances in those patients.

Assessment of cytokine release after in vitro stimulation of whole blood with legionella pneumophila in immunocompromised patients.

This study we examined ex vivo potential of the immune response after stimulation of whole blood with L. pneumophila SG 1, SG 2-14 and L. pneumophila standard strain ATCC 33152 in immunocompromised patients, such as: hemodialysis patients and patients after renal transplantation. The levels of TNF-α and IFN-γ in supernatants were measured with the use of commercial ELISA kits. The synthesis of TNF-α and IFN-γ after stimulation with L. pneumophila were analyzed in two aspects: differentiated stimulatory activity in relation to SG 1, SG 2-14 and ATCC 33152 L. pneumophila and differentiated response of the hemodialysis patients and patients after renal transplantation in relation to the control group. The positive and negative results of anti-L. pneumophila antibodies of two groups of our patients were found for the analysis of the stimulatory activity of L.pneumophila as a primary or secondary response. In patients with immunosuppression the response in the secretion of cytokines (TNF-α and IFN-γ) was reduced after stimulation of L. pneumophila SG 1 but in varying degrees after stimulation of L. pneumophila SG 2-14, which indicates that the risk of the infection is varied.

Evaluation of immature monocyte-derived dendritic cells generated from patients with colorectal cancer

UNLABELLED Dendritic cells are heterogeneous population of the leukocytes and most potent APC in activation of naive T lymphocytes. Therefore the DCs generated in vitro are under research for their application in anti-tumor immunotherapy. The aim of the study was generation of the immature dendritic cells from peripheral blood monocytes collected from colorectal cancer patients and comparison of their ability to endocytosis, cytokine production and immunophenotype to DCs generated from healthy donors. MATERIAL AND METHODS 16 adenocarcinoma stage II patients were included in the study. Dendritic cells were generated in the presence of rhGM-CSF and IL-4. PBMC were isolated from the blood of patients and 16 healthy donors - control group. Immunophenotype, ability of endocytosis of Dextran- FITC as well as intracellular IL-12 expression of the generated dendritic cells was measured using flow cytometry. The cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration in the supernatants of DCs culture was measured by ELISA. RESULTS The percentage of the immature dendritic cells and expression of CD206 and CD209 antigens was significantly higher in patients group (p <0.05 and p <0.001 respectively). Significantly (p <0.001) higher expression of the antigens which initiate the Th2 immune response (CD80-/CD86 + and B7-H2 + / CD209 +) was in the patients group. There were no differences in endocytosis ability and the cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration between investigated groups. CONCLUSIONS High immature markers expression on the generated dendritic cells together with identical endocytosis ability in patients group is advantageous in antitumor autologous cells immunotherapy planning. However there is one troubling fact--high expression of markers, which may induce tolerance to particular antigen. It seems to be more reasonable to use the autologous DCs in the antitumor immunotherapy, especially due to the incompatibility in allogenic cells in the context of HLA complex.

Prevalence of Legionella antibodies in immunocompromised patients

IntroductionDialysis patients and patients post-renal transplantation can be predisposed to Legionella infections. The aim of this work was to investigate the prevalence of L. pneumophila serogroups 1–7 (SG 1–7) antibodies in dialysis patients and in patients following renal transplantation, in order to analyse the potential risk factors for infections.Material and MethodsCommercial ELISA kits were used for detection of serum IgG (SG 1–7, SG 1) and IgM (SG 1–7) present in patients and the control group. Results: In the studied group of patients, positive results (IgM and/or IgG SG 1–7) were obtained in 20 patients (7.12%). One patient only had two classes of antibodies. From the total study group, the antibodies against L. pneumophila SG 1 were detected in only one patient on dialysis. Patients with L. pneumophila antibodies who are on dialysis or post-renal transplantation did not differ significantly in any of the usually evaluated risk factors of clinical infection.ConclusionsThe reported outbreaks of Legionnaires’ disease in chronic dialysis patients and those with renal transplants, as well as our results of IgG and IgM antibodies, merit further identification of the sources of this infection but also the ways in which cellular immune system can be managed in the immunocompromised patients with Legionella infection.

Organ Retrieval in Donors Suspected of Cancer: Single-Center Experience

BACKGROUND The transmission of cancerous cells with a transplanted organ is among the most serious complications of transplant surgery. Detailed preoperative tests seek to reduce the risk of transmission of viral and bacterial infections as well as to prevent donor-derived malignancy following organ transplantation. The objective of this study was to report our experience among cadaveric donors who we suspected of cancer. MATERIALS AND METHODS We performed a retrospective search of the medical records of 75 potential cadaveric donors referred to our unit between January 2007 and December 2010. Our focus, however, was on donors suspected of cancer. RESULTS Among 75 potential cadaveric donors 22 (29%) revealed features suggestive of cancer: physical signs of tumor pre- or intraoperatively: elevation of serum levels of a cancer marker; or an abnormal finding on radiological imaging. Among the latter group, 15 donors necessitated urgent histopathologic examination to rule out or confirm cancer. In four cases, organ transplantation was abandoned following the examination, including three cases in which a tissue diagnosis of cancer was evident and in one case, the examination was inconclusive to exclude cancer. In the remaining 14 cases, the histopathologic examination did not reveal cancer; thus transplantation was performed. CONCLUSIONS Thorough histopathologic examination is essential in all potential donors who are suspected of cancer to prevent donor-derived malignancy following transplantation. In some cases, however, the tissue sampling is not conclusive; hence, transplantation must be abandoned. Even the most precise examination of the donor does not protect the recipient from the risk of transmission of cancer.

Varices of the Descending Duodenum Explored During Emergency Gastro-Duodenal Resection for Upper Gastrointestinal Haemorrhage. Case Report

Upper gastrointestinal haemorrhage is a major medical emergency and accounts for approximately 7,000 admissions to hospitals in Scotland each year. Over the last 10 years there has been a number of improvements in diagnosis and conservative management of the condition, which significantly reduced the ratio of life-threatening cases requiring an emergency surgery. Despite these achievements surgical intervention or, if accessible, endovascular procedures must be undertaken as emergency actions, should conservative management fail. Vascular malformations of the duodenum are less frequent causes of upper GI bleeding. Duodenal varices found endoscopically occur in 0.4% of patients with portal hypertension (PHT) and are believed to be caused mainly by liver cirrhosis, idiopathic PHT, extrahepatic PHT, or previous surgical trauma. The duodenal bulb is their most common site, followed by the second portion of the duodenum. Forty per cent of patients with PHT have duodenal varices at angiography; however, their penetration unusually affects submucosa, hence no symptoms develop. Isolated bleeding duodenal varices are scarcely reported in literature, although present a significant surgical problem: massive haemorrhage combined with failure to identify them as a source has led to catastrophic outcomes with mortality rate of 40%. The case hereby presented is unique in several aspects. Duodenal varices were explored on emergency laparotomy rather than on prior endoscopies, which, performed by the same well-established endoscopists, were twice negative. This corresponds to the study by Cottam et al. stating that duodenal varices may not penetrate the submucosa, hence haemorrhages of their origin may even be more difficult to diagnose on endocsopy. Secondly, the haemorrhage here reported was undoubtedly a life-threatening condition that required a multidisciplinary team to be managed successfully. Along with Shirashi et al. we confirm that surgical ligation followed by the excision of duodenal / small intestinal varices may be an effective method of their management--both cases have been free of recurrence at 15 months postoperatively. In contrast to the study by Hashizume et al. the duodenal varices here presented were not associated with portal hypertension (PTH). Finally, duodenal varices located in the posterolateral aspect of the descending duodenum are less common as the majority of cases reported so far were of duodenal bulb location.