KH Elisabethinen

Linz, Austria

KH Elisabethinen

Linz, Austria
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PubMed | Red Cross, Regional Blood Transfusion Center, Institute of Hematology and Transfusion Medicine and KH Elisabethinen
Type: Case Reports | Journal: Transfusion | Year: 2016

The Rhesus (Rh) complex consists of a core comprising the Rh proteins (RhD/RhCE) and the Rh-associated glycoprotein (RhAG) with accessory chains (GPB, LW, CD47). Molecular defects of the RHAG gene may cause a regulator Rhnull phenotype without Rh antigen expression or a Rhmod phenotype with decreased Rh antigen expression.Blood samples of a donor with strongly diminished Rh antigens and five family members were analyzed by serological phenotyping, flow cytometry, molecular testing, and gene expression analysis of Rh complex candidate genes.RHAG sequencing identified a missense mutation, c.241G>C (p.Gly81Arg) and a splice site mutation, c.640 + 3del14, among the cohort. Compound heterozygosity of these novel alleles identified in the propositus and two siblings gave rise to a strongly diminished expression of RhAG, Rh, and CD47 antigens on the RBC surface.The Rhmod phenotype was caused by a novel RHAG splice site mutation in association with a non-functional allele. The primary depression of RhAG is most likely due to posttranslational events that affect the interaction and processing of the RhAG glycoprotein and gave rise to a secondary depression of RhD, RhCE, and CD47, the major members of the Rh complex.

Magpantay L.,Medical University of Vienna | Ziai F.,Medical University of Vienna | Oberbauer R.,KH Elisabethinen | Haas M.,Medical University of Vienna
Journal of Renal Nutrition | Year: 2011

Objective: Transplant recipients are generally instructed to increase their daily fluid intake so as to preserve kidney function. However, studies supporting this hypothesis are lacking. Setting: Prospective, randomized study at a tertiary care university hospital. Patients: Patients with chronic kidney transplant failure. Intervention: Assignment to normal fluid intake (NFI: 2 L/day) or high fluid intake (HFI: 4 L/day) for 12 months. Main Outcome Measure: The effect of fluid intake on the decrease in estimated glomerular filtration rate (eGFR) was estimated by a mixed-effects general linear model. The analysis was adjusted for the observation period, age, intake of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers, diuretics, and transplant duration. Results: A total of 33 patients were randomized to NFI and 29 to HFI. After 12 months, the mean eGFR had decreased to a similar extent in both groups (NFI: 44 ± 9 mL/min vs. 41 ± 9 mL/min; HFI: 46 ± 15 mL/min vs. 44 ± 15 mL/min). In the multivariate analysis, only the observation period had a significant effect on the decrease in eGFR. Randomization to NFI or HFI nor any other variable was associated with kidney function. The association between urine volume and urine osmolality was lost after 12 months. Conclusions: Recommendation of higher fluid intake does not seem to improve chronic kidney transplant failure. However, the lack of association between urine osmolality and reported urine volume at a later stage implies a loss of adherence to fluid intake over time. © 2011 National Kidney Foundation, Inc.

Amatschek S.,KH Elisabethinen | Amatschek S.,Medical University of Vienna | Wilflingseder J.,KH Elisabethinen | Wilflingseder J.,Medical University of Vienna | And 9 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival. Methods: A placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation. Results: Of the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p = 0.40 and p = 0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR = 0.63 95% CI [0.29, 1.36], p = 0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR = 1.02 95% CI [0.50, 2.10], p = 1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death. Conclusions: Steroid pretreatment of organ donors did not improve outcomes after liver transplantation. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Kainz A.,KH Elisabethinen | Kainz A.,Medical University of Vienna | Wilflingseder J.,KH Elisabethinen | Wilflingseder J.,Medical University of Vienna | And 4 more authors.
Transplant International | Year: 2012

Anemia is a common problem after renal transplantation. Therefore, the patients are treated with erythropoietin stimulating agents (ESAs). The varying response to treatment contributes to hemoglobin variability, which might be associated with mortality. We conducted a retrospective cohort study of first kidney allograft recipients between 1990 and 2008 represented in the Austrian Transplant Registry. We included 1441 patients of whom 683 received ESAs at any time after transplantation. Cox regression with cubic splines and linear estimates and the purposeful selection algorithm of covariables were used. The measure of variability was the moving standard deviation computed at three monthly intervals for the entire graft life. The hazard ratio (HR) of mortality and graft loss in the spline models increased with hemoglobin variability. The linear HR for mortality was 2.35 (95% confidence interval 1.75-3.17, P < 0.001) and functional graft loss 2.45 (1.76-3.40, P < 0.001). In an adjusted Cox model (ESA use, hemoglobin, age, diabetes, days on dialysis, eGFR, biopsy confirmed acute rejection and year of transplantation), hemoglobin variability was associated with mortality (HR: 2.11; 1.51-2.94; P < 0.001). No association with functional graft loss could be detected (HR: 1.34; 0.93-1.93; P = 0.121). These findings suggest that hemoglobin variability is associated with mortality of renal allograft recipients. © 2012 European Society for Organ Transplantation.

Amatschek S.,KH Elisabethinen | Haller M.,KH Elisabethinen | Oberbauer R.,KH Elisabethinen | Oberbauer R.,Medical University of Vienna
European Journal of Clinical Investigation | Year: 2010

Background: Renal reabsorption of inorganic phosphate is critical for the maintenance of phosphate homeostasis. The sodium dependent phosphate cotransporters NaPi-IIa and NaPi-IIc have been identified to fulfill this task at the brush border membrane of proximal tubule cells. Various factors including dietary phosphate intake, parathyroid hormone, or the so called phosphatonins such as FGF23 have been shown to regulate activity of these transporters. Design: This review seeks to give an update on our current knowledge about regulatory mechanisms involved in human renal phosphate reabsorption. Results: Recently, an increasing number of genes have been identified that are directly associated with inherited phosphate wasting disorders (Klotho, PHEX, DMP1 and NHERF1). Several of these genes are predominantly expressed by osteocytes and osteoclasts in the bone suggesting indispensable signalling pathways between kidneys and the skeleton. Conclusion: In this review, the affected gene products in these inherited hypophosphataemias and their contribution to phosphate homeostasis are discussed. © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

Wilflingseder J.,KH Elisabethinen | Wilflingseder J.,Medical University of Vienna | Regele H.,Medical University of Vienna | Perco P.,Emergentec Biodevelopment GmbH | And 7 more authors.
Transplantation | Year: 2013

Background. Increasing evidence accumulates on the central involvement of microRNAs (miRNAs) in disease pathophysiology. We identified distinctly deregulated miRNAs in human renal allograft biopsies from patients undergoing acute cellular rejection, antibody-mediated rejection (ABMR), and delayed graft function (DGF). Methods. Sixty-five posttransplantation kidney biopsy samples covering 41 cases with acute rejection (15 vascular rejection, 15 interstitial rejection, and 11 ABMR), 14 DGF cases, and 10 protocol biopsies serving as controls were analyzed using the Affymetrix GeneChip miRNA Array. Differentially regulated miRNAs were identified by Student's t test and Bonferroni correction. Target genes for the set of miRNAs were retrieved from miRTarBase (experimentally verified targets) as well as by applying the target prediction routines DIANAmT, miRanda, and Targetscan. Results. Patients with acute cellular rejection, ABMR, and DGF discriminate from the control group (protocol biopsies) in unsupervised clustering of miRNA profiles, clearly identifying deregulated miRNAs in rejection and DGF. Angiogenesis, apoptosis, and transforming growth factor-A signaling were identified as relevant pathways in ischemic response following an integrative analysis of miRNA targets and mRNA expression profiles. Inflammation by chemokine and cytokine signaling, T-cell activation, and B-cell activation were identified as relevant in acute rejection accordingly. Conclusion. These data suggest that distinct miRNA signatures playing a role in specific biological pathways discriminate acute cellular and humoral rejection and DGF. This finding serves as valuable tool for a rational selection of diagnostic, prognostic, and potentially therapeutic molecular targets of posttransplantation events. © 2013 Lippincott Williams & Wilkins.

Wiesbauer F.,Medical University of Vienna | Heinze G.,Medical University of Vienna | Regele H.,Medical University of Vienna | Horl W.H.,Medical University of Vienna | And 5 more authors.
Transplantation | Year: 2010

Introduction: The efficacy of tight glycemic control for the prevention of death and renal failure in the general diabetic population is well established. However, in diabetic renal-allograft recipients, the effect of different treatment strategies on outcomes is undetermined. Methods: We conducted a cohort study of 798 diabetic, renal-allograft recipients transplanted at the Medical University of Vienna between 1990 and 2004. We studied the influence of glucose parameters and diabetes treatment on mortality and graft loss. Marginal-structural models and multivariable Cox regression analysis were used to control for confounding. Results: Maximal glucose levels but not HbA1c were independently associated with mortality. Being in the highest quartile of maximal glucose increased the adjusted risk of death by a factor of 2.2 (P value for trend 0.009). Furthermore, in patients receiving insulin, the risk of death was increased 1.7-fold (95% confidence interval 0.9-3.1) compared with diet and 2.0-fold (95% confidence interval 1.1-3.7) compared with oral medication. Maximal glucose, HbA1c, or diabetes treatment did not influence death-censored functional graft survival. Discussion: In conclusion, maximal glucose levels and insulin treatment were independently associated with higher rates of mortality in our cohort of diabetic, renal-allograft recipients. However, graft survival was unaffected. Copyright © 2010 by Lippincott Williams & Wilkins.

Kainz A.,KH Elisabethinen | Kainz A.,Medical University of Vienna | Mayer B.,Emergentec Biodevelopment GmbH | Kramar R.,Austrian Dialysis and Transplant Registry | And 2 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. Anaemia is a common complication in dialysis patients. In most cases, it is treated with erythropoietinstimulating agents (ESA). It is not entirely clear whether the variability of haemoglobin caused by changing ESA response is associated with increased mortality. Therefore, we conducted a retrospective cohort study to evaluate ESA responsiveness and haemoglobin variability in association with mortality. Methods. We used the Austrian dialysis and transplant registry, and identified 932 patients who were on maintenance haemodialysis in the years 2005-08 with recorded weekly ESA doses and haemoglobin concentrations. ESA response was defined as a positive regression slope over the observation period. Cox regression analysis with spline functions and purposeful variable selection algorithms were used. Results. Adjusted Cox regression analysis showed an increased mortality risk in subjects with wide ranges of haemoglobin variability (from <10 to > 12 g/dL) (HR = 2.38, 95% CI 1.20-4.71, P = 0.013). Furthermore, patients that never reached haemoglobin levels >10 g/dL despite ESA therapy exhibited the highest risk of mortality (HR = 6.37, 95% CI 2.15-18.82, P < 0.001). ESA hypo-responsiveness was associated with increased risk of mortality in the low as well as high haemoglobin ranges [HR = 2.06, 95% CI 1.49-2.86 at haemoglobin of 9.5 g/dL and HR = 1.64, 95% CI 0.68-3.92 at 13.5 g/dL both vs. 11 g/dL (reference)]. ESA dose equivalents >16 000 units per week were associated with increased mortality in ESA responders (HR = 1.30, 95% CI 1.02-1.64). However, in hypo-responders, mortality is not associated with ESA dose (HR = 1.02, 95% CI 0.87-1.20) [both at weekly ESA dose of 20 000 units vs. 16 000 (reference)]. Conclusions. These findings suggest that the risk of mortality of haemodialysis patients requiring ESA therapy is lowest if the haemoglobin concentration is stably maintained in the range between 10 and 12 g/dL with weekly ESA dose equivalents <16 000 units. © The Author 2010.

Reindl-Schwaighofer R.,KH Elisabethinen | Oberbauer R.,KH Elisabethinen | Oberbauer R.,Medical University of Vienna
Transplantation Reviews | Year: 2014

Post transplant anemia (PTA) is a common issue in kidney transplant recipients. Most importantly it is associated with an impaired allograft function. Other important factors associated with PTA are immunosuppressive drugs (MPA, AZA and SRL), iron deficiency, infections (Parvo B19), older donor age, rejection episodes, an increased inflammatory state, and erythropoietin hyporesponsiveness. As there are no adequately powered RCTs in the kidney transplant population on anemia treatment with ESA, we have to rely on what we know from the large RCTs in the CKD population. The recently published KDIGO guidelines do not recommend treatment with ESA if Hb is >. 10. g/dl. Repletion of iron stores is emphasized. Post transplant leukopenia (PTL) and thrombocytopenia (PTT) are frequent complications especially in the first six months after kidney transplantation. Myelosuppression caused by immunosuppressive agents (MPA, AZA, SRL, rATG), antimicrobial drugs (VGCV), and CMV infection is the predominant cause. There are no widely accepted guidelines on treatment strategies, but most often dose reduction or discontinuation of causative medication is done. Most clinicians tend to decrease MPA dose, but this is eventually associated with an increase in acute rejection episodes. VGCV dose reduction (preemptive treatment instead of CMV prophylaxis) may be a successful strategy. In severe cases G-CSF treatment is an important management option and seems to be safe. © 2014 Elsevier Inc.

Kainz A.,Medical University of Vienna | Wilflingseder J.,Medical University of Vienna | Mitterbauer C.,Medical University of Vienna | Haller M.,KH Elisabethinen | And 5 more authors.
Annals of Internal Medicine | Year: 2010

Background: Posttransplantation acute renal failure (ARF) occurs in roughly 25% of recipients of organs from deceased donors. Inflammation in the donor organ is associated with risk for ARF. Objective: To determine whether administering corticosteroids to deceased organ donors reduces the incidence and duration of ARF in organ recipients more than placebo. Design: Parallel, blocked randomized trial, performed between February 2006 and November 2008, with computer-generated randomization and centralized allocation. Investigators were masked to group assignment. ( registration number: ISRCTN78828338) Setting: 3 renal transplantation centers in Austria and Hungary. Patients: 306 deceased heart-beating donors and 455 renal transplant recipients. Interventions: Organ donors were administered an intravenous infusion of either 1000 mg of methylprednisolone (136 donors) or placebo (0.9% saline) (133 donors) at least 3 hours before organ harvesting. Measurements: Incidence of ARF, defined as more than 1 dialysis session in the first week after transplantation, was the primary end point. Secondary and other end points included duration of ARF and trajectories of serum creatinine level. The suppression of immune response and inflammation by the intervention was assessed in the donor organ on a genome-wide basis. Results: 52 of 238 recipients (22%) of kidneys from steroid-treated donors and 54 of 217 recipients (25%) of kidneys from placebo-treated donors had ARF (difference, 3 percentage points [95% CI, -11 to 5 percentage points]). One graft was lost on day 1 in each group, and 1 recipient in the placebo group died of cardiac arrest on day 2. The median duration of ARF was 5 days (interquartile range, 2 days) in the steroid group and 4 days (interquartile range, 2 days) in the placebo group (P = 0.31). The groups had similar trajectories of serum creatinine level in the first week (P = 0.72). Genomic analysis showed suppressed inflammation and immune response in kidney biopsies from deceased donors who received corticosteroids. Limitation: Donors and recipients were mainly white, and all were from 3 transplantation centers in central Europe, which may limit generalizability. Conclusion: Systemic suppression of inflammation in deceased donors by corticosteroids did not reduce the incidence or duration of posttransplantation ARF in allograft recipients. Primary Funding Source: Austrian Science Fund and Austrian Academy of Science. © 2010 American College of Physicians.

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