Vimentin cleavage in end-stage renal disease is not related to apoptosis

Open Medicine ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Felix Liebscher ◽  
Tobias Arnold ◽  
Ying Liang ◽  
Thomas Reiter ◽  
Georg Böhmig ◽  
...  
Keyword(s):  
Renal Disease ◽  
Healthy Volunteers ◽  
End Stage Renal Disease ◽  
Caspase 3 ◽  
Vimentin Expression ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

AbstractAnti-vimentin auto-antibodies contribute to chronic allograft nephropathy. They exist in sera of end-stage renal disease patients on hemodialysis (ESRD) already before renal transplantation. We found recently that a 49 kDa vimentin fragment is increased in lymphocytes of ESRD patients which is presented on the cell surface. In vitro studies showed that such a fragment is formed during apoptosis by active caspase-3. We hypothesized that vimentin degradation in leukocytes of ESRD patients correlates to caspase-3 activation in vivo. Lymphocytes and monocytes were isolated from ESRD patients and from healthy volunteers and analyzed for vimentin expression and caspase-3 activation. In addition, apoptosis was induced in vitro and quantified by flow cytometry. ESRD monocytes have shown only the full length 60 kDa vimentin isoform. ESRD lymphocytes, however, showed in addition a strongly increased expression of the 49 kDa vimentin in all samples. Caspase-3 activation was found in 60% of ESRD lymphocytes and 66% of ESRD monocytes but not in healthy volunteers. UV-mediated induction of apoptosis was not associated with vimentin degradation. These experiments could confirm increased vimentin degradation in ESRD lymphocytes. However, we could not validate any correlation to apoptosis.

scholarly journals Single-Dose Pharmacokinetics, Safety, and Tolerability of Albinterferon Alfa-2b in Subjects with End-Stage Renal Disease on Hemodialysis Compared to Those in Matched Healthy Volunteers

2010 ◽  
Vol 55 (2) ◽  
pp. 473-477 ◽  
Author(s):  
Denise B. Serra ◽  
Haiying Sun ◽  
Sylwia Karwowska ◽  
Jens Praestgaard ◽  
Atef Halabi ◽  
...  
Keyword(s):  
Renal Disease ◽  
Healthy Volunteers ◽  
End Stage Renal Disease ◽  
Hepatitis C Virus Infection ◽  
Time Curve ◽  
And Gender ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Laboratory Adverse Event

ABSTRACTAlbinterferon alfa-2b (albIFN) is being developed, in combination with ribavirin, for the treatment of hepatitis C virus infection. This study was designed to evaluate the pharmacokinetics, safety, and tolerability of a 900-μg dose of albIFN administered as a single subcutaneous injection in end-stage renal disease (ESRD) patients on hemodialysis and matched healthy volunteers (by age [±5 years], weight [±5 kg], and gender). The maximum concentration in plasma (Cmax) and the area under the concentration-time curve from time zero to infinity (AUC0-∞) were 42.8 ± 14.0 ng/ml and 16,414 ± 4,203 ng·h/ml, respectively, for healthy volunteers, while theCmaxand AUC0-∞were 49.9 ± 20.9 ng/ml and 18,919 ± 8,008 ng·h/ml, respectively, for ESRD patients. The geometric least-squares mean ratios were 1.15 (90% confidence interval [CI], 0.78, 1.68) forCmaxand 1.11 (90% CI, 0.83, 1.48) for AUC0-∞. Adverse events were as expected for an interferon (e.g., flu-like symptoms), with the main laboratory adverse event being a decline in total white blood cell count, which was specifically related to a decline in the neutrophil count. This effect was somewhat greater in the ESRD patients, with the maximal decreases in neutrophil counts from those at the baseline being (−2.6 ± 0.32) × 109and (−2.19 ± 0.58) × 109cells/liter for the ESRD patients and the healthy volunteers, respectively. This study indicates no significant effect of renal failure on the pharmacokinetics of albIFN. Safety and tolerability were as expected for an interferon.

Differences between KT/V Measured during Dialysis and KT/V Predicted from Manufacturer Clearance Data

1992 ◽  
Vol 15 (8) ◽  
pp. 465-469 ◽  
Author(s):  
L.K. Saha ◽  
J.C. Van Stone
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Urea Clearance ◽  
Blood Flows ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

We retrospectively analyzed data from 3,863 dialysis treatments in 329 end-stage renal disease patients over a period of 33 months to evaluate the accuracy of in vitro KT/V estimated by manufacturer's urea clearance data in relation to in vivo measured KT/V. In 1,087 urea clearances measured, mean actual clearance was 87% of predicted. At all blood flows, actual clearances were significantly lower than predicted (8-16% lower than predicted). In 2,807 KT/V measurements, predicted KT/V was 1.238 ± 0.005 whereas the mean of actual measured KT/V was 16% lower or 1.024 ± 0.005 (P < 0.0001). At different blood flows and with different dialyzers, predicted KT/V overestimated actual values. With increasing numbers of reuse, actual/predicted clearance ratios and actual/predicted KT/V ratios progressively dropped. Prescribing dialysis treatments using manufacturer's in vitro generated clearance data can lead to marked underdialysis of patients.

scholarly journals A potential role of fecal oxalate-degrading activity in oxalate homeostasis in end-stage renal disease patients; a descriptive pilot study

2021 ◽  
Vol 10 (3) ◽  
pp. e19-e19
Author(s):  
Natalia Stepanova ◽  
Ganna Tolstanova ◽  
Lesya Korol ◽  
Iryna Akulenko ◽  
Olena Savchenko ◽  
...  
Keyword(s):  
Pilot Study ◽  
Renal Disease ◽  
Healthy Volunteers ◽  
Effect Size ◽  
End Stage Renal Disease ◽  
Potential Role ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Introduction: End-stage renal disease (ESRD) patients have significant differences in plasma oxalic acid (POx) concentration under the same treatment conditions. Objectives: In the present study, we adopted the method of redoximetric titration with a KMnO4 solution to evaluate the effect of total fecal oxalate-degrading activity (ODA) on oxalate homeostasis in ESRD patients which has never been reported before. Patients and Methods: A total of 56 participants were enrolled in this cross-sectional pilot study, including 24 healthy volunteers (a control reference group) and 32 ESRD patients. Among the ESRD patients, there were 21 hemodialysis (HD) and 11 peritoneal dialysis (PD) patients. Total ODA in fecal samples as well as POx concentration, daily urinary oxalate (UOx) and PD effluent oxalate excretion were determined. Cohen’s d was computed to calculate the effect size using post-hoc analysis. Results: Total ODA in fecal microbiota ranged from -23 to 24%/0.01 g of feces and was statistically higher in healthy volunteers compared with the ESRD patients. The ESRD patients with positive total fecal ODA status had higher UOx excretion level and lower POx concentration compared with the patients with negative total fecal ODA status. Cohen’s d effect size was 1.99 and 1.05, respectively. Total fecal ODA was an independent risk factor associated with POx elevation in the ESRD patients. Conclusion: Our pilot study firstly demonstrated a potential role of total fecal ODA in oxalate homeostasis in ESRD patients. The results might be useful for determining sample size considerations and providing groundwork for future research projects.

Increased Levels of Anaphylatoxin (C5a) and Bradykinin in End-Stage Renal Disease Patients on Maintenance Hemodialysis. Potential Relevance to Heparin Mediated Hemodynamic Responses

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4079-4079
Author(s):  
Cafer Adiguzel ◽  
Vinod Bansal ◽  
Josephine Cunanan ◽  
Evangelos Litinas ◽  
Debra Hoppensteadt ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Sandwich Elisa ◽  
Maintenance Hemodialysis ◽  
Control Group ◽  
Contact Activation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Abstract Besides the upregulation of inflammatory mediators, end stage renal disease (ESRD) patients maintained on hemodialysis are subjected to periodic exposure to heparin and contact activation due to procedural settings. Recently the presence of a heparin contaminant, namely hypersulfated chondroitin sulfate was linked with the adverse reactions and deaths observed in these patients (Kishmoto, et al. N J Med 2008). To validate this report we measured both the C5a anaphlatoxin and bradykinin levels in ESRD patients prior to and after maintenance hemodialysis. The control group comprised of 40 normal healthy individuals were included to establish the normal level of these mediators. A sandwich ELISA method utilizing a monoclonal antibody which is specific for human C5a and bradykinin were used in these studies. Both the C5a and bradykinin were elevated in pre-dialysis samples from ESRD patients (C5a: 3.2±0.6 ng/ml vs 14.2± 4.6 ng/ml, bradykinin: 6.4±1.8 ng/ml vs 9.3±2.4 ng/ml). Moreover, dialysis itself produced an increase in both the C5a and bradykinin levels. Moreover, the postdialysis samples were further increased, suggesting that dialysis and heparinization itself result in the up-regulation of these mediators. Supplementation of heparin to the plasma also resulted in the generation of both C5a and bradykinin. The plasma samples included in these studies represents patients who were not treateded with the contaminant heparin. Additional studies on in-vitro generation of these markers with contaminated heparin and the isolated contaminant showed that both of these triggered the generation of C5a and bradyknin. These results suggest that both C5a and bradykinin are up-regulated in ESRD patients and this level can be further augmented by dialysis and heparinization. Therefore, additional factors may have contributed to the complex adverse reaction profiles and deaths in patients administrated with contaminated heparin.

scholarly journals 41Ca and Accelerator Mass Spectrometry to Monitor Calcium Metabolism in End Stage Renal Disease Patients

2005 ◽  
Vol 51 (11) ◽  
pp. 2095-2102 ◽  
Author(s):  
Robert L Fitzgerald ◽  
Darren J Hillegonds ◽  
Douglas W Burton ◽  
Terrance L Griffin ◽  
Scott Mullaney ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bone Resorption ◽  
Renal Disease ◽  
Accelerator Mass Spectrometry ◽  
End Stage Renal Disease ◽  
Isotope Ratios ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Abstract Background: Monitoring bone resorption with measurements of bone density and biochemical markers is indirect. We hypothesized that bone resorption can be studied directly by serial measurements of the ratio 41Ca/Ca in serum after in vivo labeling of calcium pools with 41Ca. We report the preparation of an intravenous 41Ca dose suitable for humans, an analytical method for determining 41Ca/Ca isotope ratios in biological samples, and studies in human volunteers. Methods: 41Ca was formulated and aliquoted into individual vials, and to the extent possible, the 41Ca doses were tested according to US Pharmacopeia (USP) guidelines. A 10 nCi dose of 41Ca was administered intravenously to 4 end stage renal disease (ESRD) patients on hemodialysis and 4 healthy control individuals. Distribution kinetics were determined over 168 days. Calcium was isolated with 3 precipitation steps and a cation-exchange column, and 41Ca/Ca ratios in serum were then measured by accelerator mass spectrometry. Results: The dosing solution was chemically and radiologically pure, contained &lt;0.1 endotoxin unit/mL, and passed USP sterility tests. Quantification of 41Ca/Ca ratios was linear from 6 × 10−14 to 9.1 × 10−10. The run-to-run imprecision (as CV) of the method was 4% at 4.6 × 10−11 and 6% at 9.1 × 10−10. The area under the curve of 41Ca in the central compartment vs time was significantly less for ESRD patients than for controls (P &lt;0.005). Conclusions: Isotope ratios spanning 5 orders of magnitude can be measured by accelerator mass spectrometry with excellent precision in the range observed in samples collected from patients who have received 10 nCi of 41Ca. The 41Ca at this dose caused no adverse effects in 8 volunteers. This is the first report of the use of 41Ca to monitor differences in bone turnover between healthy individuals and ESRD patients.

scholarly journals Increased carbamylation level of HDL in end-stage renal disease: carbamylated-HDL attenuated endothelial cell function

2016 ◽  
Vol 310 (6) ◽  
pp. F511-F517 ◽  
Author(s):  
Jia Teng Sun ◽  
Ke Yang ◽  
Lin Lu ◽  
Zheng Bin Zhu ◽  
Jin Zhou Zhu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Paraoxonase 1 ◽  
Healthy Control ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

It is thought that carbamylated modification plays a crucial role in the development and progression of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). However, information on the biological effects of carbamylated high-density lipoprotein (C-HDL) in ESRD is poor. The present study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy control subjects ( n = 22) and patients with ESRD ( n = 30). The carbamylation level of HDL was detected using ELISA. Isolated C-HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells were treated with C-HDL or native HDL to assess their migration, proliferation, and angiogenesis properties. HDL-associated paraoxonase 1 activity was also determined by spectrophotometry assay. Compared with healthy control subjects, the carbamylation level of HDL in ESRD patients was increased and positively correlated with blood urea concentration. In vitro, C-HDL significantly inhibited migration, angiogenesis, and proliferation in endothelial cells. Mechanistic studies revealed that HDL-associated paraoxonase 1 activity was decreased and negatively correlated with the carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of VEGF receptor 2 and scavenger receptor class B type I signaling pathways in endothelial cells. In conclusion, the present study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair functions.

Adipokines and Gut Hormones in End-Stage Renal Disease

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 298-302
Author(s):  
Robert H. Mak ◽  
Wai Cheung
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Poor Quality ◽  
Mortality And Morbidity ◽  
Novel Therapeutic Strategies ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Cachexia is common in end-stage renal disease (ESRD) patients, and it is an important risk factor for poor quality of life and increased mortality and morbidity. Chronic inflammation is an important cause of cachexia in ESRD patients. In the present review, we examine recent evidence suggesting that adipokines or adipocytokines such as leptin, adiponectin, resistin, tumor necrosis factor α, interleukin-6, and interleukin-1β may play important roles in uremic cachexia. We also review the physiology and the potential roles of gut hormones, including ghrelin, peptide YY, and cholecystokinin in ESRD. Understanding the molecular pathophysiology of these novel hormones in ESRD may lead to novel therapeutic strategies.

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