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Linz, Austria

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. Source

Wilflingseder J.,Medical University of Vienna | Sunzenauer J.,KH Elisabethinen | Toronyi E.,Semmelweis University | Heinzel A.,Emergentec Biodevelopment GmbH | And 6 more authors.
PLoS ONE | Year: 2014

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI. © 2014 Wilflingseder et al. Source

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. Source

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. Source

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. (Controlled-trials.com 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. Source

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