| 1. |
- Carrero, J.J., et al.
(författare)
-
Telomere attrition is associated with inflammation, low fetuin : A levels and high mortality in prevalent haemodialysis patients
- 2008
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 263:3, s. 302-312
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Chronic kidney disease (CKD) predisposes to a 10- to 20-fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. METHODS: This is a cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23-86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient's leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2-42) months. RESULTS: Telomere length was shorter in CKD men, despite women being older (average +/- SD 6.41 +/- 1.23 vs. 6.96 +/- 1.48 kb, P = 0.002). Telomere length was associated with age (rho = -0.18, P = 0.01), fetuin-A (rho = 0.26, P = 0.0004), high-sensitivity C-reactive protein (rho = -0.21, P = 0.005) and IL-6 (rho = -0.17, P = 0.02). In a multivariate logistic regression (pseudo r(2) = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin-A levels. CONCLUSION: Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin-A.
|
|
| 2. |
|
|
| 3. |
- Stenvinkel, Peter, et al.
(författare)
-
Statin treatment and diabetes affect myeloperoxidase activity in maintenance hemodialysis patients
- 2006
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450 .- 1555-905X. ; 1:2, s. 281-287
-
Tidskriftsartikel (refereegranskat)abstract
- Myeloperoxidase (MPO), which is secreted during activation of neutrophils, may serve as one mechanistic link among persistent inflammation, oxidative stress, and cardiovascular disease. This study related MPO activity to inflammatory and oxidative stress biomarkers, comorbidity, and ongoing medication in prevalent hemodialysis (HD) patients. In a cross-sectional evaluation of 115 prevalent (vintage 25 mo) HD patients (62 men; 63 +/- 1 yr), data on comorbidity (Davies score), diabetes, medication (statins and antiltypertensive drugs), nutritional status (subjective global assessment), blood lipids (cholesterol, HDL cholesterol, and triglycerides), inflammatory biomarkers (serum albumin, C-reactive protein, TNF-alpha, and IL-6), oxidative stress biomarkers (pentosidine, 8-hydroxydeoxyguanosine, and MPO activity) were recorded. Patients with MPO activity greater than the median had significantly (P < 0.05) lower serum albumin levels (33.2 +/- 0.7 versus 35.0 +/- 0.5 g/L), higher 8-hydroxydeoxyguanosine levels (1.26 +/- 0.08 versus 1.05 +/- 0.06 ng/mb, and a lower prevalence of statin treatment (18 versus 36%). Therefore, the median MPO activity was significantly (P < 0.05) lower (17.7 versus 26.6 Delta OD630/min per mg protein) in the subgroup of 31 HD patients with ongoing statin treatment. In a multiple regression model, correction for the impact of age, gender, vintage, serum cholesterol, serum albumin, comorbidity, diabetes, and statin use, only diabetes (P < 0.01) and statin use (P < 0.01) were significantly associated to MPO activity. Fourteen patients who had diabetes and were receiving statin treatment had markedly (P = 0.001) lower median (19.9 versus 41.2 Delta OD630/min per mg protein) MPO activity compared with 18 who had diabetes and were not taking statins. This cross-sectional study suggests that both diabetes and statin treatment affect MPO activity in prevalent HD patients.
|
|
| 4. |
- Bárány-Wallje, Elsa, et al.
(författare)
-
A critical reassessment of penetratin translocation across lipid membranes.
- 2005
-
Ingår i: Biophys J. - 0006-3495. ; 89:4, s. 2513-21
-
Tidskriftsartikel (refereegranskat)abstract
- Penetratin is a short, basic cell-penetrating peptide able to induce cellular uptake of a vast variety of large, hydrophiliccargos. We have reassessed the highly controversial issue of direct permeation of the strongly cationic peptide across negatively charged lipid membranes. Confocal laser scanning microscopy on rhodamine-labeled giant vesicles incubated with carboxyfluorescein-labeled penetratin yielded no evidence of transbilayer movement, in contradiction to previously reported results. Confocal fluorescence spectroscopy on black lipid membranes confirmed this finding, which was also not affected by application of a transmembrane electric potential difference.A novel dialysis assay based on tryptophan absorbance and fluorescence spectroscopy demonstrated that the permeability of small and large unilamellar vesicles to penetratin is,<10^-13m/s.Taken together, the results show that penetratin is not capable of overcoming model membrane systems irrespective of the bilayer curvature or the presence of a transmembrane voltage. Thus, direct translocation across the hydrophobic core of the plasmamembrane cannot account for the efficient uptake of penetratin into live cells, which is in accord with recent in vitro studies underlining the importance of endocytosis in the internalization process of cationic cell-penetrating peptides.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Elinder, Carl-Gustaf, et al.
(författare)
-
Variations in graft and patient survival after kidney transplantation in Sweden: caveats in interpretation of center effects when benchmarking.
- 2009
-
Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:11, s. 1051-7
-
Tidskriftsartikel (refereegranskat)abstract
- Benchmarking and comparisons between transplantation centers are becoming more common. A crude comparison indicated a 50% difference in patient survival between centers in Sweden. A 'task group' was formed to refute or confirm and learn from this observation. Patient survival and graft survival of 5 933 patients transplanted at three different transplantation centers in Sweden (Stockholm, Göteborg, and Malmö) were followed up until February 2007. Patient survival and graft survival were compared between the centers with and without consideration being given to important covariates such as time period, type of donation (living or deceased donor), gender, and age. A refined cohort of 2,956 adult patients that had been transplanted for the first time between 1991 and 2007 was assessed in more detail using Cox regression analysis. The difference in patient and transplant outcome observed in the crude comparison diminished considerably after adjustment for differences in case mix and time period of transplantation, and was neither evident nor significant after 1999. Patient survival and graft survival have improved considerably during the time period since 1991. The adjusted hazards ratio for mortality was 0.39 (95% CI 0.29-0.53) for patients who were transplanted after 1999 when compared with those transplanted between 1991 and 1994. Crude comparisons between results from transplantation centers may be severely confounded not only by case mix but also by differences in the proportion of patients transplanted during different time periods. Patient outcome and graft outcome have improved considerably since 1991, and after 1999 center effects were no longer apparent in Sweden.
|
|
| 8. |
- Furuland, Hans, 1956-
(författare)
-
Effects of Hemoglobin Normalization with Epoetin in Chronic Kidney Disease
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.
|
|
| 9. |
- Hayashi, Shirley Yumi, et al.
(författare)
-
Left ventricular function in patients with chronic kidney disease evaluated by colour tissue Doppler velocity imaging
- 2006
-
Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 21:1, s. 125-132
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD) patients. Tissue Doppler velocity imaging (TVI) is a new objective method that accurately quantifies myocardial tissue velocities, deformation, time intervals and left ventricular (LV) filling pressure. In this study, TVI was compared with conventional echocardiography for the assessment of left ventricular (LV) function in pre-dialysis patients with different stages of CKD. The results obtained by TVI were used to analyse possible relationships between LV function and clinical factors such as hyperparathyroidism and hypertension that could influence LV function. Methods. Conventional echocardiography and TVI images were recorded in 40 patients (36 men and 4 women, mean age 60 +/- 14 years, range 28-80 years) and in 27 healthy controls (21 men and 6 women, mean age 58 +/- 17 years, range 28-82 years). Twenty-two patients had mild/moderate CKD (CCr > 29 ml/min; Group 1) and 18 patients had severe CKD (CCr <= 29 ml/min; Group 2). Using TVI, the myocardial tissue velocities (v; cm/s) for isovolumetric contraction (IVCv), peak systole (PSv), early (E') and late (A') diastolic filling velocities as well as strain rate (SR), mitral annulus displacement, isovolumetric relaxation time (IVRT) and LV filling pressure were estimated using TVI. The average of six LV wall measurements was used to evaluate LV global function. Results. Using TVI, we were able to identify significantly more patients with diastolic dysfunction than using conventional echocardiography (33 vs 26, P < 0.05). There was no difference in the prevalence of diastolic dysfunction between Group 1 and 2. However, using TVI, Group 2 CKD patients had lower E' velocities (6.2 +/- 1.9 vs 8.0 +/- 2.9 cm/s, P < 0.05) and higher IVRT (137.4 +/- 13 vs 88.2 +/- 26 ms, P < 0.001) in comparison with controls, indicating more accentuated diastolic dysfunction. Systolic blood pressure (SBP) was associated with E' velocities (rho = -0.68, P < 0.005) and E'/A' was strongly associated with SBP (rho = -0.60; P < 0.01) and PTH (rho = -0.64, P < 0.005) in Group 2. Using conventional echocardiography, there was no difference in the prevalence of systolic and diastolic dysfunction between patients with and without LVH. However, using TVI, patients with LVH had significantly lower IVCv (2.8 +/- 1.3 vs 3.8 +/- 1.5 and 3.8 +/- 1.5 cm/s, P < 0.05) and PSv (5.5 +/- 1.0 vs 6.3 +/- 1.2 and 6.4 +/- 1.3 cm/s, P < 0.05) compared with patients without LVH and controls, and they also had lower E' velocities (7.1 +/- 2.7 vs 8.0 +/- 2.9 cm/s, P < 0.05) compared with controls, indicating disturbances in systolic and diastolic left ventricular function. Conclusions. TVI provided additional information on left ventricular function in CKD patients. In patients with advanced renal failure, TVI revealed more accentuated diastolic dysfunction associated with increased systolic blood pressure (SBP) and increased levels of PTH. TVI also demonstrated disturbances in contractility and contraction in patients with LVH, which could not be detected by conventional echocardiography.
|
|
| 10. |
|
|
