@article{StoppePatelZarbocketal.2023, author = {Stoppe, Christian and Patel, Jayshil J. and Zarbock, Alex and Lee, Zheng-Yii and Rice, Todd W. and Mafrici, Bruno and Wehner, Rebecca and Chan, Man Hung Manuel and Lai, Peter Chi Keung and MacEachern, Kristen and Myrianthefs, Pavlos and Tsigou, Evdoxia and Ortiz-Reyes, Luis and Jiang, Xuran and Day, Andrew G. and Hasan, M. Shahnaz and Meybohm, Patrick and Ke, Lu and Heyland, Daren K.}, title = {The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial}, series = {Critical Care}, volume = {27}, journal = {Critical Care}, doi = {10.1186/s13054-023-04663-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357221}, year = {2023}, abstract = {Background Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI. Methods In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated. Results Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95\% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95\% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT. Conclusions In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT. Trial registration: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.}, language = {en} } @article{GreiteStoermerGueleretal.2022, author = {Greite, Robert and St{\"o}rmer, Johanna and Gueler, Faikah and Khalikov, Rasul and Haverich, Axel and K{\"u}hn, Christian and Madrahimov, Nodir and Natanov, Ruslan}, title = {Different acute kidney injury patterns after renal ischemia reperfusion injury and extracorporeal membrane oxygenation in mice}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {19}, issn = {1422-0067}, doi = {10.3390/ijms231911000}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288282}, year = {2022}, abstract = {The use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidney during surgery. In this study, we aimed to explore the kidney injury patterns in mouse models of ECMO and renal IRI. Kidneys of C57BL/6 mice were examined after moderate (35 min) and severe (45 min) unilateral transient renal pedicle clamping and 2 h of veno-venous ECMO. Renal injury markers, neutrophil infiltration, tubular transport function, pro-inflammatory cytokines, and renal heme oxygenase-1 (HO-1) expression were determined by immunofluorescence and qPCR. Both procedures caused AKI, but with different injury patterns. Severe neutrophil infiltration of the kidney was evident after renal IRI, but not following ECMO. Tubular transport function was severely impaired after renal IRI, but preserved in the ECMO group. Both procedures caused upregulation of pro-inflammatory cytokines in the renal tissue, but with different time kinetics. After ECMO, but not IRI, HO-1 was strongly induced in tubular cells indicating contact with hemolysis-derived proteins. After IRI, HO-1 was expressed on infiltrating myeloid cells in the tubulo-interstitial space. In conclusion, renal IRI and ECMO both caused AKI, but kidney damage after renal IRI was more pronounced including severe neutrophil infiltration and tubular transport impairment. Enhanced HO-1 expression in tubular cells after ECMO encourages limitation of hemolysis as a therapeutic approach to reduce ECMO-associated AKI.}, language = {en} } @article{AverdunkBernhagenFehnleetal.2020, author = {Averdunk, Luisa and Bernhagen, J{\"u}rgen and Fehnle, Karl and Surowy, Harald and L{\"u}decke, Hermann-Josef and Mucha, S{\"o}ren and Meybohm, Patrick and Wieczorek, Dagmar and Leng, Lin and Marx, Gernot and Leaf, David E. and Zarbock, Alexander and Zacharowski, Kai and Bucala, Richard and Stoppe, Christian}, title = {The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {9}, issn = {2077-0383}, doi = {10.3390/jcm9092936}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213126}, year = {2020}, abstract = {Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5-7}\) (rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23\% vs. 13\%; OR 2.01 (1.40-2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8\% vs. 0.4\%; OR 5.12 (0.99-33.14), p = 0.026). The GC genotype was associated with AKI (20\% vs. GG/CC:13\%, OR 1.71 (1.20-2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46-3.09), p < 0.001) and death (OR 5.58 (1.29-24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.}, language = {en} } @article{MagyarWagnerThomasetal.2019, author = {Magyar, Attila and Wagner, Martin and Thomas, Phillip and Malsch, Carolin and Schneider, Reinhard and St{\"o}rk, Stefan and Heuschmann, Peter U and Leyh, Rainer G and Oezkur, Mehmet}, title = {HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study}, series = {International Journal of Nephrology and Renovascular Disease}, volume = {12}, journal = {International Journal of Nephrology and Renovascular Disease}, doi = {10.2147/IJNRD.S165308}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177250}, pages = {9-18}, year = {2019}, abstract = {Background: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. Patients and methods: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. Results: AKI with an incidence of 23.3\% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). Conclusion: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.}, language = {en} } @article{TerposKleberEngelhardtetal.2015, author = {Terpos, Evangelos and Kleber, Martina and Engelhardt, Monika and Zweegman, Sonja and Gay, Francesca and Kastritis, Efstathios and van de Donk, Niels W. C. J. and Bruno, Benedetto and Sezer, Orhan and Broijl, Annemiek and Bringhen, Sara and Beksac, Meral and Larocca, Alessandra and Hajek, Roman and Musto, Pellegrino and Johnsen, Hans Erik and Morabito, Fortunato and Ludwig, Heinz and Cavo, Michele and Einsele, Hermann and Sonneveld, Pieter and Dimopoulos, Meletios A. and Palumbo, Antonio}, title = {European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications}, series = {Haematologica}, volume = {100}, journal = {Haematologica}, number = {10}, doi = {10.3324/haematol.2014.117176}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141913}, pages = {1254 -- 1266}, year = {2015}, abstract = {The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging. In asymptomatic myeloma, bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given continuously, but it is not clear if patients who achieve at least a very good partial response benefit from its continuous use (grade 1B). Treatment with erythropoietic-stimulating agents may be initiated in patients with persistent symptomatic anemia (hemoglobin < 10g/dL) in whom other causes of anemia have been excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if no adequate hemoglobin response is achieved. For renal impairment, bortezomib-based regimens are the current standard of care (grade 1A). For the management of treatment-induced peripheral neuropathy, drug modification is needed (grade 1C). Vaccination against influenza is recommended; vaccination against streptococcus pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or valacyclovir) is recommended for patients receiving proteasome inhibitors, autologous or allogeneic transplantation (grade 1A).}, language = {en} } @article{SchickBaarFlemmingetal.2014, author = {Schick, Martin A. and Baar, Wolfgang and Flemming, Sven and Schlegel, Nicolas and Wollborn, Jakob and Held, Christopher and Schneider, Reinhard and Brock, Robert W. and Roewer, Norbert and Wunder, Christian}, title = {Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model}, series = {Intensive Care Medicine Experimental}, volume = {2}, journal = {Intensive Care Medicine Experimental}, number = {34}, doi = {10.1186/s40635-014-0034-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126111}, year = {2014}, abstract = {Background Up to 50\% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. Methods Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. Results All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. Conclusions The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI.}, language = {en} } @article{NassWeissbrichHuberetal.2012, author = {Nass, Maximilian and Weissbrich, Benedikt and Huber, Moritz and Schneider, Elisabeth Marion and Weiss, Manfred}, title = {BK viremia in critically ill surgical patients with hemorrhagic or septic shock}, series = {BMC Research Notes}, volume = {5}, journal = {BMC Research Notes}, number = {100}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124136}, year = {2012}, abstract = {Background Infections with polyomavirus BK virus (BKV) are a common cause of renal dysfunction after renal transplantation and may also be harmful in surgical patients with shock. The aim of the present study was to determine the frequency of BKV viremia in critically ill surgical patients with septic or hemorrhagic shock, and, if viremia is detectable, whether viremia may be associated with renal dysfunction. Findings A total of 125 plasma samples from 44 critically ill surgical patients with septic or hemorrhagic shock were tested by real-time polymerase chain reaction (PCR) for BKV DNA during their stay on the intensive care unit (ICU). BKV viremia occurred in four patients, i.e. in three of the septic and in one of the hemorrhagic shock group. There was no association between viremia and renal dysfunction. All positive samples contained a low viral load (< 500 copies/ml). Conclusions Since BK viremia was rarely found and with low viral load only in critically ill surgical patients with shock, it is very unlikely that BK viremia results in BK nephropathy later on.}, language = {en} } @article{BrevoordKrankeKuijpersetal.2012, author = {Brevoord, Daniel and Kranke, Peter and Kuijpers, Marijn and Weber, Nina and Hollmann, Markus and Preckel, Benedikt}, title = {Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0042179}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134471}, pages = {e42179}, year = {2012}, abstract = {Background: Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. Methods and Results: Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95\% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference -0.28 [-0.47, -0.09]). Conclusion: There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.}, language = {en} }