Stylianos Panagoutsos

Effects of L-carnitine on oxidative stress responses in patients with renal disease.

PURPOSE Hemodialyzed patients demonstrate elevated oxidative stress and reduced functional status. Exercise induces health benefits, but acute exertion up-regulates oxidative stress responses in patients undergoing hemodialysis. Therefore, the aim of the present study was to examine the effect of L-carnitine supplementation on i) exercise performance and ii) blood redox status both at rest and after exercise. METHODS Twelve hemodialysis patients received either L-carnitine (20 mg kg(-1) i.v.) or placebo in a double-blind, placebo-controlled, counterbalanced, and crossover design for 8 wk. Participants performed an exercise test to exhaustion before and after supplementation. During the test, V˙O2, respiratory quotient, heart rate, and time to exhaustion were monitored. Blood samples, collected before and after exercise, were analyzed for lactate, malondialdehyde, protein carbonyls, reduced and oxidized glutathione, antioxidant capacity, catalase, and glutathione peroxidase activity. RESULTS Blood carnitine increased by L-carnitine supplementation proportionately at rest and after exercise. L-carnitine supplementation increased time to fatigue (22%) and decreased postexercise lactate (37%), submaximal heart rate, and respiratory quotient but did not affect V˙O2peak. L-carnitine supplementation increased reduced/oxidized glutathione (2.7-fold at rest, 4-fold postexercise) and glutathione peroxidase activity (4.5% at rest, 10% postexercise) and decreased malondialdehyde (19% at rest and postexercise) and protein carbonyl (27% at rest, 40% postexercise) concentration. CONCLUSIONS Data suggest that a 2-month L-carnitine supplementation may be effective in attenuating oxidative stress responses, enhancing antioxidant status, and improving performance of patients with end-stage renal disease.

Timely transfer of peritoneal dialysis patients to hemodialysis improves survival rates.

AIMS The two main renal replacement therapies (RRT)--hemodialysis (HD) and peritoneal dialysis (PD)--have been considered to be antagonistic in most published studies on the clinical outcomes of dialysis patients. Recently, it has been suggested that the complementary use of both modalities as an integrated care (IC) strategy might improve the survival rate of end-stage renal disease patients. The aim of this study was to estimate the final clinical outcome of PD patients when they transfer to HD because of complications related to PD. MATERIALS AND METHODS We retrospectively analyzed data from the following patients that started RRT during the last 10 years: 33 PD patients (IC group; age 55 +/- 15 years, mean +/- SD) who transferred to HD, 134 PD patients (PD group, age 64 +/- 11 years) who remained in PD, and 132 HD patients (HD group, age 48 +/- 16 years) who started and continued in HD. The main reasons for the transfer to HD were relapsed peritonitis and loss of ultrafiltration, while various comorbid risk factors were adjusted by Cox hazards regression model (age, presence of diabetes or/and cardiovascular disease, serum hemoglobin and albumin levels, as well as the modality per se). RESULTS 3- and 5-year survival rates for the IC, PD and HD groups were 97% and 81%, 54% and 28%, and 92% and 83%, respectively. The 5-year survival rate was significantly higher in IC patients than in PD patients (p < 0.00001) but, was not different from that in HD patients. CONCLUSIONS Our results show that the IC of dialysis patients undergoing RRT improves the survival of patients on PD if they are transferred to HD upon the appearance of PD related complications.

Acute exercise may exacerbate oxidative stress response in hemodialysis patients.

Background/Aims: Hemodialyzed patients (HD) demonstrate elevated oxidative stress (OXS) levels. Exercise effects on OXS response and antioxidant status of HD was investigated in the present study. Methods: Twelve HD and 12 healthy controls (HC) performed a graded exercise protocol. Blood samples, collected prior to and following exercise, were analyzed for lactate, thiobarbituric acid-reactive substances (TBARS), protein carbonyls (PC), reduced (GSH) and oxidized glutathione (GSSG), total antioxidant capacity (TAC), catalase, and glutathione peroxidase (GPX) activity. Results: HC demonstrated higher time-to-exhaustion (41%), lactate (41%) and VO2 peak (55%) levels. At rest, HD exhibited higher TBARS, PC, and catalase activity values and lower GSH, GSH/GSSG, TAC, and GPX levels. Although exercise elicited a marked change of OXS markers in both groups, these changes were more pronounced (p < 0.05) in HD patients. After adjusting for VO2 peak, differences between groups disappeared. VO2 peakwas highly correlated with GSH/GSSG, TBARS, TAC and PC at rest and after exercise. Conclusions: These results imply that HD demonstrate higher OXS levels and a lower antioxidant status than HC at rest and following exercise. Acute exercise appears to exacerbate OXS response in hemodialyzed patients probably due to diminished antioxidant defense. However, aerobic capacity level seems to be related to OXS responses in this population.

Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients

BACKGROUND Increased arterial stiffness and aortic blood pressure (BP) are independent predictors of cardiovascular outcomes in end-stage renal disease. The 3-day interdialytic interval is associated with elevated risk of cardiovascular morbidity and mortality in haemodialysis. This study investigated differences in ambulatory aortic BP and arterial stiffness between the second and third day of the long interdialytic interval. METHODS Ambulatory BP monitoring with Mobil-O-Graph monitor (IEM, Stolberg, Germany) was performed in 55 haemodialysis patients during a 3-day interval. Mobil-O-Graph records oscillometric brachial BP and pulse waves and calculates aortic BP and augmentation index (AIx) as measure of wave reflections, and pulse wave velocity (PWV) as measure of arterial stiffness. RESULTS Ambulatory aortic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher during the third versus second interdialytic day (123.6 ± 17.0 versus 118.5 ± 17.1 mmHg, P < 0.001; 81.5 ± 11.8 versus 78 ± 11.9 mmHg, P < 0.001, respectively). Similar differences were noted for brachial BP. Ambulatory AIx and PWV were also significantly increased during the third versus second day (30.5 ± 9.9 versus 28.8 ± 9.9%, P < 0.05; 9.6 ± 2.3 versus 9.4 ± 2.3 m/s, P < 0.001, respectively). Differences between Days 2 and 3 remained significant when day-time and night-time periods were compared separately. Aortic SBP and DBP, AIx and PWV showed gradual increases from the end of dialysis session onwards. Interdialytic weight gain was a strong determinant of the increase in the above parameters. CONCLUSIONS This study showed significantly higher ambulatory aortic BP, AIx and PWV levels during the third compared with the second interdialytic day. These findings support a novel pathway for increased cardiovascular risk during the third interdialytic day in haemodialysis.

Chromosome instability in patients with chronic renal failure.

OBJECTIVE The aim of this study was to investigate the frequency of sister chromatid exchanges (SCEs), the presence of cytostaticity, cytotoxicity, and therefore, the possible genetic instability in patients with chronic renal failure (CRF) in human cultured peripheral blood lymphocytes. METHODS Peripheral blood lymphocytes were cultured from 32 patients with CRF (average 55.2 years) and 18 healthy blood donors (average 44.6 years), and the SCE method was applied afterward. The increase in SCE frequency was evaluated as an immediate DNA damage index, while the reduction in the values of the proliferating rate indices was evaluated as a cytostatic index and the mitotic indices as a cytotoxic index was also measured. RESULTS A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls. It is notable that there was no significant difference in SCE levels among patients with CRF and cancer, and patients with CRF alone. CONCLUSIONS This study illustrates increased genetic instability in patients with CRF. These results could also be of a great importance in early diagnosis to prognosticate a possible generation of neoplasm in the future.

Low T3 syndrome and long-term mortality in chronic hemodialysis patients.

AIM To investigate the predictive value of low freeT3 for long-term mortality in chronic hemodialysis (HD) patients and explore a possible causative role of chronic inflammation. METHODS One hundred fourteen HD patients (84 males) consecutively entered the study and were assessed for thyroid function and two established markers of inflammation, high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Monthly blood samples were obtained from all patients for three consecutive months during the observation period for evaluation of thyroid function and measurement of inflammatory markers. The patients were then divided in two groups based on the cut-off value of 1.8 pg/mL for mean plasma freeT3, and were prospectively studied for a mean of 50.3 ± 30.8 mo regarding cumulative survival. The prognostic power of low serum fT3 levels for mortality was assessed using the Kaplan-Meier method and univariate and multivariate regression analysis. RESULTS Kaplan-Meier survival curve showed a negative predictive power for low freeT3. In Cox regression analysis low freeT3 remained a significant predictor of mortality after adjustment for age, diabetes mellitus, hypertension, hsCRP, serum creatinine and albumin. Regarding the possible association with inflammation, freeT3 was correlated with hsCRP, but not IL-6, and only at the first month of the study. CONCLUSION In chronic hemodialysis patients, low plasma freeT3 is a significant predictor of all-cause mortality. Further studies are required to identify the underlying mechanisms of this association.

Pivotal Role of Paricalcitol in the Treatment of Calcific Uremic Arteriolopathy in the Presence of a Parathyroid Adenoma

Calcific uremic arteriolopathy, or calciphylaxis, is a serious and life-threatening complication of end-stage renal disease. Its pathogenesis is not yet fully elucidated and treatment is controversial. In the presence of severe hyperparathyroidism, parathyroidectomy should be considered. We report a case of a woman on maintenance hemodialysis therapy with calciphylaxis and parathyroid adenoma who refused to undergo parathyroidectomy. She was treated successfully with a combination of noncalcium phosphate binders, cinacalcet, and paricalcitol. Subcutaneous plaques disappeared, and the necrotic lesion was healed. Discontinuation of paricalcitol led to an increase in serum parathyroid hormone levels and reappearance of the patients symptoms, whereas its reintroduction resulted in complete remission of the clinical picture. Paricalcitol, a less calcemic vitamin D analogue, is also a selective vitamin D receptor activator with a number of nonclassic actions (such as inhibition of inflammation and ossification-calcification) that could prove beneficial in cases of calciphylaxis.

Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy

AIMS We sought to determine the predictive value of Matrix Gla Protein MGP T-138C polymorphism in relation to all-cause mortality, cardiovascular mortality and cardiovascular events in patients with diabetic nephropathy (DN). METHODS MGP T-138C polymorphism was assessed in 40 diabetic patients without nephropathy and 118 patients at different stages of DN, including patients on hemodialysis. Measurement of carotid intima-media thickness (cIMT) was performed using real-time B-mode ultrasonography. Plasma levels of dephoshorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) were determined in a subgroup of 67 patients by ELISA. Mortality and cardiovascular events were assessed during a 7year follow-up. RESULTS TT homozygotes for the MGP T-138C polymorphism had higher values of cIMT compared to combined TC and CC genotypes (P=0.006) whereas no association was observed between cIMT and dp-ucMGP levels. MGP T-138C polymorphism was a strong independent predictor of cIMT (P<0.0001), after adjustment for several well-known atherosclerosis risk factors. Patients with TT genotype presented a significantly higher all-cause and cardiovascular mortality risk compared to patients with TC and CC genotypes (P=0.01 and P=0.04 respectively), after adjustment for several traditional risk factors. CONCLUSIONS MGP T-138C polymorphism is a strong and independent predictor of increased cIMT as well as all-cause and cardiovascular mortality in DN patients.

Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus

Background: Inflammation plays a pivotal role in the pathogenesis of diabetes and its complications. Arachidonic acid lipoxygenases have been intensively studied in their role in inflammation in metabolic pathways. Thus, we aimed to explore variants of lipoxygenase genes (arachidonate lipoxygenase genes) in a diabetes adult population using a case-control study design. Methods: Study population consisted of 1285 elderly participants, 716 of whom had type 2 diabetes mellitus. The control group consisted of non-diabetes individuals with no history of diabetes history and with a glycated haemoglobin <6.5% (<48 mmol/mol)] and fasting plasma glucose levels <126 mg/dL. Blood samples were genotyped on Illumina Infinium PsychArray. Variants of ALOX5, ALOX5AP, ALOX12, ALOX15 were selected. All statistical analyses were undertaken within PLINK and SPSS packages utilising permutation analysis tests. Results: Our findings showed an association of rs9669952 (odds ratio = 0.738, p = 0.013) and rs1132340 (odds ratio = 0.652, p = 0.008) in ALOX5AP and rs11239524 in ALOX5 gene with disease (odds ratio = 0.808, p = 0.038). Rs9315029 which is located near arachidonate ALOX5AP also associated with type 2 diabetes mellitus (p = 0.025). No variant of ALOX12 and ALOX15 genes associated with disease. Conclusion: These results indicate a potential protective role of ALOX5AP and 5-arachidonate lipoxygenase gene in diabetes pathogenesis, indicating further the importance of the relationship between diabetes and inflammation. Larger population studies are required to replicate our findings.

Brucellosis in dialysis patients. Does it exist

BACKGROUND Brucellosis is a zoonotic disease transmittable to humans. It is diagnosed either by isolation of Brucella organism in culture of blood or other sample types (e.g., bone marrow or liver biopsy specimens), or by a combination of serological tests and clinical findings. Dialysis patients constitute a special population group with an impaired autoimmune system and a propensity to develop infections, such as brucellosis. This paper presents the high incidence of brucellosis in our dialysis patients during last year, while there was not any zoonotic infection recorded in the previous at least 5 year period. METHODS-RESULTS This is a retrospective study including 8 dialysis patients, undergoing renal replacement therapies (5 patients were on hemodialysis (HD) and 3 on peritoneal dialysis (PD)), who out of a total of 124 patients developed brucellosis, during the last year. Four patients were male and four female and their mean age was 67 +/- 9 years. Clinical presentation of Brucellosis infection was mild with low-grade fever and symptoms of influenza. All patients were living in places where animal brucellosis was prevalent. Infection was diagnosed on the basis of clinical symptoms and signs and with polymerase chain reaction (PCR) analysis of peripheral blood. The affected patients had consumed fresh unpasteurized milk and cheese and were treated with oral doxycycline and oral rifampicin for 6 weeks. All patients are in follow up for at least 1 year, during which there were no relapses. CONCLUSIONS Brucellosis is a zoonotic disease that can occur in dialysis patients who are susceptible to infection under certain conditions. Our brucellosis patients lived in agricultural and veterinary areas and had consumed unpasteurized milk and cheese and insufficiently cooked meat derived from infected animals.