Papers by George Tsirpanlis
Nephrology Dialysis Transplantation
Background and Aims Recent advances in the treatment of Autosomal Dominant Polycystic Kidney Dise... more Background and Aims Recent advances in the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) highlight the interplay between the clinical and the laboratory profile of the disease. This study aims to present the baseline characteristics of patients followed in a large ADPKD cohort from a single center in Greece, and explore possible associations between demographic, clinical and laboratory parameters. Method Patients followed in a specialized outpatient PKD clinic from December 2018 up to December 2019 were recruited in this study. At enrollment, demographics, medical and family history and laboratory data were recorded using a standardized form. Estimated glomerular filtration rate (eGFR) was calculated and Magnetic Resonance Imagining for total kidney volume (TKV) measurement was performed. Results One-hundred three females and 83 males with a mean age±SD of 41.4 ± 13 years (18.8 % < 30 years) were enrolled. Overall, 60.8% of them were classified as Chronic Kidn...
American Journal of Kidney Diseases, 2008
Cellular senescence is associated with shortened or damaged telomeres and is characterized by per... more Cellular senescence is associated with shortened or damaged telomeres and is characterized by permanent exit from the cell cycle, morphological changes, and altered function. It develops after repeated cell divisions and also can be induced prematurely by stress conditions. The senescent phenotype, depending on cell type and atherosclerosis phase, seems to be a proatherosclerotic one: it promotes endothelial dysfunction and appears to be implicated in plaque destabilization, as well as in endothelial progenitor cell alteration. Many traditional and nontraditional cardiovascular disease risk factors induce senescence in a variety of vascular cells. Several of these factors, such as diabetes, hypertension, oxidative stress, and inflammation, are clustered in patients with chronic kidney disease. In a limited number of recent studies, stress-induced premature cellular senescence in this biologically aged population also was described. The hypothesis that premature cellular senescence might be considered an additional atherosclerosis-inducing factor in patients with chronic kidney disease is proposed.
Kidney and Blood Pressure Research, 2004
Recently, Chlamydia pneumoniae is the microorganism frequently implicated in the infection-based ... more Recently, Chlamydia pneumoniae is the microorganism frequently implicated in the infection-based inflammatory atherogenous hypothesis. Although in vitro experimental data and initial sero-epidemiologic, pathology-based studies and antibiotic trials supported this interesting hypothesis, later data are conflicting. Some confounding factors are the causes of uncertainty; lacking of standard methods for C. pneumoniae detection, co-existence of other atherosclerotic risk factors and anti-inflammatory effects of antibiotics used in clinical trials seem to be the principal ones. Standardization of methodology used, antibiotic trials with a different orientation-design and a vaccine preparation that eventually will be tested in clinical trials with a long follow-up, should provide a definite answer regarding the probability C. pneumoniae to be a main, a secondary or an irrelevant factor to atherosclerosis. Studies linking C. pneumoniae to inflammation and accelerated atherosclerosis in renal failure patients are accumulated but limitations are similar to the above mentioned.
Kidney and Blood Pressure Research, 2005
In the last few years atherosclerosis has been recognized as an inflammatory process. Assessment ... more In the last few years atherosclerosis has been recognized as an inflammatory process. Assessment of low-grade inflammation with indexes like C-reactive protein (CRP) is considered indicative and potentially predictive for this disease. On the other hand, in a large number of clinical studies, a grade of microinflammation has been found to be associated with numerous other processes that may be directly, indirectly or not related to atherosclerosis. The most interesting finding these studies have yielded is that innate immunity is activated in various, previously unexpected, conditions. This phenomenon is better explained by the application of a recently proposed immune activation mechanism, namely, the &amp;amp;#39;danger model&amp;amp;#39;. It seems that many conditions related to metabolic or homeostatic stress or to pro-atherosclerotic and pre-diabetic dysfunctions, established atherosclerosis or diabetes, but also other early tissue injury -- like renal, pulmonary or connective tissue -- and several exogenous stimuli, constitute &amp;amp;#39;danger signals&amp;amp;#39; that induce inflammation which interacts with and complicates the above-mentioned processes. On this basis the complex relationships between CVD risk factors, atherosclerotic process, other tissue injury and inflammation is examined. The practical application of this hypothesis, namely the new clinical use of CRP as a sensitive -- although not specific for atherosclerosis -- index of low-grade inflammatory activity as well as to the atherosclerosis treatment are also discussed.
Kidney and Blood Pressure Research, 2005
Inflammatory indexes are frequently elevated in end-stage renal failure (ESRF) patients. It seems... more Inflammatory indexes are frequently elevated in end-stage renal failure (ESRF) patients. It seems that the pattern of inflammation is particular in this population. In the presence of a higher than normal microinflammatory background (CRP, C-reactive protein, values between 0.1 and 10-15 mg/l) that varies with time, waves of &amp;amp;amp;amp;#39;true&amp;amp;amp;amp;#39; inflammation (CRP &amp;amp;amp;amp;gt; 10-15 mg/l), mainly due to infections, are added periodically. To accurately assess the average microinflammation in these patients, multiple CRP measurements are required. As recent experimental studies showed that inflammation and particularly elevated CRP levels may be risk factors and not just a risk index for atherosclerosis, in this case, the characteristic inflammation pattern might be of importance in the evolution of this disease in ESRF patients. The causes of the inflammatory state in ESRF patients are multiple: renal insufficiency per se and its complications, coexisting diseases, established atherosclerosis, the consequences of renal replacement treatment, and frequent infections are potentially the main ones. The fluctuating inflammatory pattern is probably due to destabilization or changes in time of the above-mentioned parameters. Thus, the clinical meaning of the average microinflammation in these patients, as assessed by CRP measurements, seems to be that of an index indicative of the grade of their health aggravation by the multiple factors implicated in the inflammation formation. CRP is a sensitive, but not specific, risk index of the overall morbidity and mortality in these patients. The manipulation of the inflammation in ESRF patients should include follow-up and treatment of all the factors that contribute to this state and probably medications such as the statins. If inflammation and CRP in particular definitely prove to be risk factors for atherosclerosis, intensification of this treatment will be necessary.
Blood Purification, 2009
Although cellular senescence and inflammation have been indirectly associated, a direct connectio... more Although cellular senescence and inflammation have been indirectly associated, a direct connection was absent until recently, when two studies proved that senescence at a cellular level is directly linked to an interleukin (IL)-dependent inflammatory network. IL-6 and IL-8, two well-known proinflammatory cytokines, seem to play a central role in premature cellular senescence induction. Activation of the above-mentioned molecules and their receptors is necessary for the initiation of senescence while their deactivation ceases the process. Taking in consideration that atherosclerosis is an inflammatory process and cellular senescence is an emerging cardiovascular risk factor, these new data may be of great importance, especially for chronic kidney disease patients who suffer from increased cardiovascular disease morbidity.
Blood Purification, 2007
Atherosclerosis and vascular calcification often co-exist in chronic kidney disease (CKD) patient... more Atherosclerosis and vascular calcification often co-exist in chronic kidney disease (CKD) patients. Although the former has been recently recognized as an active inflammatory process, atherosclerosis-related calcification of the intima is still viewed as a passive epiphenomenon. Recent experimental data showed that ossification of the internal vascular wall might also be an active inflammatory process interrelated to atherosclerosis. Factors like RANKL (receptor activator of nuclear factor kappaB ligand), RANK and osteoprotegerin modulate vascular calcification and at the same time are involved in the process of atherosclerosis. Moreover, basic calcium phosphate crystals could interact with and activate monocytes-macrophages that produce proinflammatory cytokines capable of initiating - via endothelial activation and leukocyte adhesion - the atherosclerotic process. Thus, vascular calcification might be an active player and not simply an epiphenomenon in atherosclerosis. Should the above-mentioned data be confirmed in future studies, calcification of the internal vascular wall and atherosclerosis might be viewed and treated as tightly interconnected and linked by inflammation processes in CKD patients.
The effect of viable Chlamydia pneumoniae on serum cytoof intercellular signaling peptides, such ... more The effect of viable Chlamydia pneumoniae on serum cytoof intercellular signaling peptides, such as cytokines, adkines and adhesion molecules in hemodialysis patients.
Background. Chlamydia pneumoniae has been implicated as an inflammatory agent in atherosclerosis.... more Background. Chlamydia pneumoniae has been implicated as an inflammatory agent in atherosclerosis. Clinical studies in this field have yielded conflicting results, which may have resulted from a lack of standardization for C.pneumoniae detection. We attempted to accurately estimate C.pneumoniae prevalence and to examine whether C.pneumoniae is associated with atherosclerosis and inflammation in haemodialysis (HD) patients. To do this, we assessed C.pneumoniae presence by a combination of methods and correlated its levels with inflammatory and atherosclerotic indexes in these patients. Methods. Chlamydia pneumoniae was identified by polymerase chain reaction (PCR) in DNA extracted from cell cultures inoculated with patient buffy coats and by serum IgG antibodies against C.pneumoniae (IgGCp). Inflammation was assessed by C-reactive protein and serum amyloid A and atherosclerosis was evaluated from clinical and laboratory data. Results. Of the 130 patients, only nine had viable C.pneumoniae in peripheral blood mononuclear cells (PBMCs) while 64 had serum IgGCp. Although patients with viable C.pneumoniae had higher athero-sclerotic scores, seropositive and negative patients showed similar scores. Patients with atherosclerosis exhibited higher inflammatory indexes. Neither patients with detectable C.pneumoniae in PBMCs nor seropositive subjects had higher inflammation than negative patients. Conclusions. We found that viable C.pneumoniae in PBMCs, assessed by cell culture and PCR, was present in a small percentage of HD patients and was correlated with atherosclerosis. Seropositivity was much higher in HD patients but was not associated with viable C.pneumoniae or with atherosclerosis. Further studies in HD patients using high sensitivity and specificity methods in larger populations will be necessary to clarify the relationship between C.pneumoniae and atherosclerosis.
Cellular and Molecular Biology Letters, 2015
Patients suffering from renal failure exhibit an impaired immune system function. We wanted to in... more Patients suffering from renal failure exhibit an impaired immune system function. We wanted to investigate the transcription of the tumor suppressor genes p53 and RB to record, if these cells could be stimulated in vitro in order to divide, after the addition of antigenic and inflammatory factors. This expression was measured by real-time PCR in peripheral blood mononuclear cells (PBMCs) from three different groups: ten healthy individuals, ten patients with chronic kidney disease (CKD), and ten dialysis patients with end stage renal disease (ESRD). The transcription rate of these genes was also measured after the cultivation of PBMCs under four different conditions: just with the culture medium, with lipopolysaccharide (LPS), with C-reactive protein (CRP), and with lipoxin A 4 (LXA 4 )-LPS. Our results show that in most cases after the cultivation with additives, the transcription levels were higher in dialysis patients compared to those of the other two groups. Our findings serve as indications of cellular senescence on a molecular level, while it seems that these cells are less easily stimulated in vitro in order to duplicate.
Pediatric Nephrology, 2005
Antiphospholipid syndrome (APS) is an autoimmune disease. Less than 1% of patients with APS prese... more Antiphospholipid syndrome (APS) is an autoimmune disease. Less than 1% of patients with APS present with life-threatening catastrophic APS (CAPS). We report here a case of CAPS in a young girl with cardiac, gastrointestinal and renal involvement. Although the management was complicated, the outcome was better than expected. We suggest that CAPS be included in the differential diagnosis of acute renal failure in children with multi-organ involvement and prolonged phospholipid-dependent coagulation time and promptly treated with immunomodulating agents and anticoagulants.
Nephrology Dialysis Transplantation, 2004
Background. Systemic microinflammation is correlated with atherosclerosis. It needs a reliable as... more Background. Systemic microinflammation is correlated with atherosclerosis. It needs a reliable assessment. This study explores the temporal variations of three inflammatory indexes [C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6)] in a period free of clinical events and tests the reliability of their multiple measurements for the assessment of microinflammation in haemodialysis (HD) patients, a population at high risk of atherosclerotic cardiovascular disease. Methods. For 4 months, serum CRP, SAA and IL-6 were measured in 29 HD patients during the weeks they were free of inflammatory clinical events (!12 measurements for each index in every patient). The components of the variance as well as the reliability of two to five measurements for each index, aimed at assessing microinflammation precisely, were computed. Results. The median (interquartile range) of CRP was 2.3 (0.9-4.9) mg/l, of SAA 3.7 (2.1-9.3) mg/l and of IL-6 4.4 (2.2-7.7) pg/ml. Patients were approximately equally distributed between three groups of low, intermediate and high variability for each index. The contribution of intraindividual (biological) variation to the total of variance was 71.3%, 69.3% and 86.7% for CRP, SAA and IL-6, respectively (higher than in all other similar studies in healthy populations). Using two measurements, the estimated reliability was 57-68% for CRP in two-thirds of the patients (comparable with that found in healthy subjects) and 57% for SAA and IL-6 in only one-third of the patients. Increasing the number of measurements up to five did not change the reliability.
Nephrology Dialysis Transplantation, 2003
Background. Chlamydia pneumoniae has been implicated as an inflammatory agent in atherosclerosis.... more Background. Chlamydia pneumoniae has been implicated as an inflammatory agent in atherosclerosis. Clinical studies in this field have yielded conflicting results, which may have resulted from a lack of standardization for C.pneumoniae detection. We attempted to accurately estimate C.pneumoniae prevalence and to examine whether C.pneumoniae is associated with atherosclerosis and inflammation in haemodialysis (HD) patients. To do this, we assessed C.pneumoniae presence by a combination of methods and correlated its levels with inflammatory and atherosclerotic indexes in these patients. Methods. Chlamydia pneumoniae was identified by polymerase chain reaction (PCR) in DNA extracted from cell cultures inoculated with patient buffy coats and by serum IgG antibodies against C.pneumoniae (IgGCp). Inflammation was assessed by C-reactive protein and serum amyloid A and atherosclerosis was evaluated from clinical and laboratory data. Results. Of the 130 patients, only nine had viable C.pneumoniae in peripheral blood mononuclear cells (PBMCs) while 64 had serum IgGCp. Although patients with viable C.pneumoniae had higher atherosclerotic scores, seropositive and negative patients showed similar scores. Patients with atherosclerosis exhibited higher inflammatory indexes. Neither patients with detectable C.pneumoniae in PBMCs nor seropositive subjects had higher inflammation than negative patients. Conclusions. We found that viable C.pneumoniae in PBMCs, assessed by cell culture and PCR, was present in a small percentage of HD patients and was correlated with atherosclerosis. Seropositivity was much higher in HD patients but was not associated with viable C.pneumoniae or with atherosclerosis. Further studies in HD patients using high sensitivity and specificity methods in larger populations will be necessary to clarify the relationship between C.pneumoniae and atherosclerosis.
Nephrology Dialysis Transplantation, 2005
Nephrology Dialysis Transplantation, 2005
Acute renal failure with severe loin pain and patchy renal ischaemia after anaerobic exercise (AL... more Acute renal failure with severe loin pain and patchy renal ischaemia after anaerobic exercise (ALPE) (exercise-induced acute renal failure) in a father and child with URAT1 mutations beyond the W258X mutation Sir, ALPE is defined as (i) acute renal dysfunction or failure due to (ii) anaerobic exercise, accompanied by (iii) loin pain and (iv) normal or only slight elevation of creatine phosphokinase or serum myoglobin . It has been reported that 51% of ALPE cases involve patients with renal hypouricaemia . After cloning of the SLC22A12 gene (URTA1: uric acid transporter 1) [3], seven renal hypouricaemic patients with exercise-induced acute renal failure were analysed for mutations of URAT1 [3-6]. Five patients were homozygotes for W258X, one patient was a heterozygote for W258X and one patient was a compound heterozygote for W258X/Q297X [3-6].
Nephrology, 2005
Background: Infectious agents may be implicated in the inflammatory atherosclerotic process. Not ... more Background: Infectious agents may be implicated in the inflammatory atherosclerotic process. Not only specific microorganisms but also the infectious burden, defined as the number of pathogens to which a patient is exposed, has been associated with atherosclerosis. In the present study, the infectious burden, determined directly (by identification of viable pathogens in peripheral blood mononuclear cells (PBMC)) and indirectly (by serum antibodies detection) is correlated to the inflammatory and atherosclerotic status in haemodialysis (HD) patients, a population at high risk for cardiovascular disease.
Nephrology, 2006
Telomerase preserves telomeres' function and structure preventing cellular senescence. Its activi... more Telomerase preserves telomeres' function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients. Methods: Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate ≥ 80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-α (TNF-α ) and interleukin-10 (IL-10) were also measured in both groups by ELISA. Results: Ox-LDL was negatively correlated to percentage telomerase activity in PBMC ( r = − 0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = − 0.559, P < 0.001 in HD patients). TNF was also inversely associated with percentage telomerase activity in the whole group studied ( r = − 0.492, P = 0.000) while IL-10 was not. In stepwise multiple linear regression, taking into consideration the most important characteristics of the HD patients and control group, the only significant predictors for percentage telomerase activity in PBMC were ox-LDL and TNF ( β = − 0.421, t = − 4.083, P = 0.000 and β= − 0.381, t = − 3.691, P = 0.000, respectively) while examining separately HD patients, the predictors for the same parameter were ox-LDL and HD duration ( β = − 0.671, t = − 4.709, P = 0.000 and β= − 0.349, t = − 2.447, P = 0.023, respectively). Conclusion: Ox-LDL serum level is inversely correlated to telomerase activity in PBMC of HD patients. Our study proposes a new consequence of increased oxidative stress in HD patients: the premature cellular senescence potentially related to atherosclerosis through LDL oxidation.
Kidney International, 2006
Kidney International, 2004
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Papers by George Tsirpanlis