Thomas Kitzler

Publications (13) View all

• Article: Efficacy of vitamin E and N-acetylcysteine in the prevention of contrast induced kidney injury in patients with chronic kidney disease: a double blind, randomized controlled trial.

  Thomas M Kitzler, Aala Jaberi, Gerald Sendlhofer, Peter Rehak, Christian Binder, Eva Petnehazy, Rudolf Stacher, Peter Kotanko
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  ABSTRACT: Contrast induced acute kidney injury is one of the most frequent causes of hospital acquired acute kidney injury. The present study aims to investigate the efficacy of vitamin E or N-acetylcysteine as an adjunct to current standard therapy in the prevention of this clinical predicament. We tested the hypothesis that vitamin E or N-acetylcysteine added to standard therapy with 0.45 % saline is superior in preserving renal function in patients with chronic kidney disease stage 1-4 undergoing elective computer-assisted tomography with nonionic radiocontrast agents when compared to 0.45 % saline alone. Prospective, randomized, single-center, double-masked, double dummy, placebo-controlled, parallel clinical trial. The patients were randomized to either vitamin E (total dose 2160 mg i.v.) or N-acetylcysteine (total dose 4800 mg p.o.) in addition to 0.45 % saline (1 mL/kg/h over 24 h) or saline alone. Serum creatinine change between baseline and 24 h after radiocontrast was the primary outcome. Contrast induced acute kidney injury was defined as a rise in serum creatinine > 25 % over the baseline value within 48 h. Thirty patients (mean age 74.6 years; 17 females; 9 diabetics; all Caucasians; mean serum creatinine 1.35 mg/dL; mean creatinine clearance 56 mL/min) were enrolled. No patient developed contrast induced acute kidney injury. There was no significant difference in serum creatinine change between the three study arms. Following radiocontrast administration, neither vitamin E nor N-acetylcystein in addition to saline demonstrated an additional beneficial effect on kidney function when compared to saline alone.
  Wiener klinische Wochenschrift 04/2012; 124(9-10):312-9. · 0.81 Impact Factor
• Article: Determination of fluid status in haemodialysis patients with whole body and calf bioimpedance techniques.

  Li Liu, Fansan Zhu, Jochen G Raimann, Stephan Thijssen, Murat H Sipahioglu, Gregory Wystrychowski, Thomas Kitzler, Ciro Tetta, Peter Wabel, Peter Kotanko, Nathan W Levin
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  ABSTRACT: The aim of this study was to demonstrate the ability of widely used bioimpedance techniques to assess dry weight (DW) and to predict a state of normal hydration in haemodialysis patients whose post-dialysis weight had been gradually reduced from baseline in successive treatments over time. Calf bioimpedance spectroscopy (cBIS) was employed to determine DW (DW(cBIS) ) as defined by flattening of an intradialytic continuously measured resistance curve and by normalized resistivity (nRho) being in the gender-specific normal range. The wECV/TBW ratio was determined by 'classical' wrist-to-ankle whole body bioimpedance spectroscopy (wBIS); in addition, a novel whole body model (WBM) based on wBIS was used to predict normal hydration weight (NHW(WBM) ). Twenty-one haemodialysis patients were studied; 11 ± 6 measurements were performed per patient. Nine patients reached DW(cBIS) (DW(cBIS) group), while 12 patients remained fluid-overloaded (non-DW(cBIS) group). Change in wECV as measured by wBIS accounted for 46 ± 23% in DW(cBIS) group, which was higher than in non-DW(cBIS) group (33 ± 48%, P < 0.05) of actual weight loss at the end of study. In both groups the wECV/TBW ratio did not change significantly between baseline and study end. Mean predicted NHW(WBM) at baseline was 3.55 ± 1.6 kg higher than DW(cBIS) . The difference in DW(cBIS) and NHW(WBM) was 1.97 ± 1.0 kg at study end. WBM could be useful to predict a target range of normal hydration weight particularly for patients with substantial fluid overload. The cBIS provides an accurate reference for the estimation of DW so that combined use of cBIS and WBM is promising and warrants further studies.
  Nephrology 09/2011; 17(2):131-40. · 1.31 Impact Factor
• Article: Complement modulates the function of the ubiquitin-proteasome system and endoplasmic reticulum-associated degradation in glomerular epithelial cells.

  Thomas M Kitzler, Joan Papillon, Julie Guillemette, Simon S Wing, Andrey V Cybulsky
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  ABSTRACT: In experimental membranous nephropathy, complement C5b-9 induces sublethal glomerular epithelial cell (GEC) injury and proteinuria. C5b-9 also activates mechanisms that restrict injury or facilitate recovery. The ubiquitin-proteasome system (UPS) selectively degrades damaged or abnormal proteins, while misfolded proteins in the endoplasmic reticulum (ER) undergo ER-associated degradation (ERAD). In this study, we investigated the effect of complement on the UPS and ERAD. We monitored UPS function by transfection of rat GECs with a UPS reporter, GFP(u) (CL1 degron fused with green fluorescent protein). By analogy, CD3δ-yellow fluorescent protein (YFP) was employed as a reporter of ERAD. We demonstrated decreased GFP(u) levels in GECs after incubation with antibody and complement, compared with control. Using C8-deficient serum with or without purified C8, cycloheximide (an inhibitor of protein synthesis), and the proteasome inhibitor, MG132, we confirmed that the decrease of GFP(u) was mediated by C5b-9, and subsequent proteasomal degradation of the reporter. Inhibition of the c-Jun N-terminal kinase attenuated the effect of complement on GFP(u) degradation. Complement, however, increased the level of CD3δ-YFP in GECs, implying an impairment of ERAD, likely due to an overabundance of misfolded proteins in the ER. The overall ubiquitination of proteins was enhanced in complement-treated GECs and in glomeruli of rats with experimental membranous nephropathy, although ubiquitin mRNA was unchanged in GECs. Proteasome inhibition with MG132 increased the cytotoxic effect of complement in GECs. Complement-stimulated UPS function, by accelerating removal of damaged proteins, may be a novel mechanism to limit complement-induced injury.
  Biochimica et Biophysica Acta 03/2012; 1823(5):1007-16. · 4.66 Impact Factor
• Article: Endoplasmic reticulum stress in glomerular epithelial cell injury.

  Andrey V Cybulsky, Tomoko Takano, Joan Papillon, Thomas M Kitzler, Krikor Bijian
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  ABSTRACT: Focal segmental glomerulosclerosis (FSGS) may be associated with glomerular epithelial cell (GEC; podocyte) apoptosis due to acquired injury or mutations in specific podocyte proteins. This study addresses mediation of GEC injury, focusing on endoplasmic reticulum (ER) stress. We studied signaling in cultured GECs in the presence or absence of the extracellular matrix (ECM). Adhesion to collagen supports cell survival, but adhesion to plastic (loss of contact with ECM) leads to apoptosis. Compared with collagen-adherent cells, GECs on plastic showed increased protein misfolding in the ER, and an adaptive-protective ER stress response, including increased expression of ER chaperones, increased phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), and a reduction in protein synthesis. Activation of these ER stress pathways counteracted apoptosis. However, tunicamycin (a potent stimulator of ER stress) changed the ER stress response from protective to cytotoxic, as tunicamycin induced the proapoptotic ER stress gene, C/EBP homologous protein-10, and exacerbated apoptosis in GECs adherent to plastic, but not collagen. In GECs adherent to plastic, adaptive ER stress was associated with an increase in polyubiquitinated proteins and "choking" of the proteasome. Furthermore, pharmacological inhibition of the proteasome induced ER stress in GECs. Finally, we show that ER stress (induction of ER chaperones and eIF2α phosphorylation) was evident in experimental FSGS in vivo. Thus interactions of GECs with ECM may regulate protein folding and induction of the ER stress response. FSGS is associated with induction of ER stress. Enhancing protective aspects of the ER stress response may reduce apoptosis and possibly glomerulosclerosis.
  AJP Renal Physiology 09/2011; 301(3):F496-508. · 4.42 Impact Factor
• Article: Proto-dialytic cardiac function relates to intra-dialytic morbid events.

  Julia Kolb, Thomas M Kitzler, Theodora Tauber, Nicholas Morris, Falko Skrabal, Peter Kotanko
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  ABSTRACT: Intra-dialytic morbid events (IDME) such as intra-dialytic hypotension (IDH) and muscle cramps frequently complicate haemodialysis (HD). Cardiac dysfunction is highly prevalent in HD patients. We investigated the relationship between proto-dialytic (i.e. early intra-dialytic) cardiac function and IDME in HD patients. Heart rate, beat-to-beat blood pressure (BP) and cardiac output were continuously measured during the first 30 min of dialysis treatment using the Task Force™ Monitor. Total peripheral resistance index (TPRI) was calculated from cardiac index (CI) and BP. Univariate, multivariate and logistic regression analyses were employed to relate IDME to haemodynamic predictors; Kaplan-Meier method was employed for time-to-event analysis. Fourteen HD patients (age 67 ± 15 years; 7 females) were studied. Dialysis treatment was complicated by IDH and muscle cramps in 4 and 8 out of 30 sessions, respectively. CI was higher in patients without IDME (2.6 ± 0.5 L/min/m(2)) as compared to those with muscle cramps (2.0 ± 0.3 L/min/m(2)) or IDH (1.8 ± 0.2 L/min/m(2); all P < 0.05). CI and TPRI at baseline independently predicted IDME in a multivariate regression analysis (odds ratio: 0.043 per unit of CI, 95% confidence interval: 0.003-0.611; odds ratio: 1.124 per unit of TPRI, 95% confidence interval: 1.25-1.01). Patients were stratified by tertiles of CI. IDME occurred in the two lower tertiles, whereas patients in the upper tertile were event free (log-rank test, P < 0.002). Low CI and high TPRI in the first 30 min of HD are associated with an increased risk of IDME.
  Nephrology Dialysis Transplantation 10/2010; 26(5):1645-51. · 3.40 Impact Factor