Effect of Difference in Serum Creatinine between Jaffe and Enzymatic Methods in Outpatient Kidney Transplant Recipients.

Background: Deviations in serum creatinine (SCr), due to its determination using a Jaffe or an enzymatic method, have an effect on kidney disease detection and staging. It is not yet clear how large this effect is in kidney transplant recipients (KTRs). SCr measurement differences are of particular importance here to evaluate the graft function. Methods: The results of all parallel SCr measurements (Jaffe and enzymatic method) of adult outpatient KTRs in the same serum sample at the University Hospital Essen (Germany) between January 2020 and October 2023 were evaluated. A Bland-Altman plot with 95% limits of agreement (LoA) was used to assess the difference between the Jaffe and the enzymatic SCr (eSCr). For all patients, we used the CKD-EPI 2009 and EKFC formula, and for patients ≥ 70 years, we also used the BIS1 formula for the determination of eGFR. Results: A total of 12,081 parallel SCr measurements from 1243 KTRs were analyzed, where 61% were male and the median age was 53 years. On average, Jaffe SCr was 0.03 mg/dL higher than eSCr (LoA -0.16; 0.21 mg/dL). On average, the eGFR determined by Jaffe SCr was 1.9 mL/min/1.73 m2 lower than the eGFR determined by eSCr (LoA -9.5; 5.7 mL/min/1.73 m2). The comparison of eGFR between the two SCr methods revealed a different CKD stage in 1589 (13%) of all analyzed measurements, most frequently between G2/G3a (41%) and G3a/G3b (24%). When using the EKFC and BIS1 formulas, there were approximately the same number of measurements leading to a different CKD stage. Conclusions: In more than every tenth SCr determination in outpatient KTRs, the difference between the Jaffe and enzymatic methods had an influence on the assignment to a CKD stage. This effect was comparably pronounced for all eGFR formulas applied.

Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism.

Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in people who are immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in patients who are immunocompromised and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with noncontrolled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hyporesponsiveness in individuals who fail to control chronic viral infection.

Comparing Flow Cytometry and ELISpot for Detection of IL-10, IL-6, and TNF Alpha on Human PBMCs.

ELISpot and flow cytometry are two methods often utilized side-by-side for detecting secreted and intracellular cytokines, respectively. Each application has its own advantages and challenges. ELISpot is more sensitive compared to ELISA and appears to be more consistent in detecting IL-10 production than flow cytometry. ELISpot can be used for detecting the secretion of multiple cytokines but not from the same cells simultaneously, whereas flow cytometry allows for the concurrent detection of multiple intracellular cytokines by the same cells. Flow cytometry is a convenient technique allowing for the detection of many cytokines at the same time in a population of cells. The restimulation cocktails used for cytokine detection in flow cytometry are hard on cells and lead to decreased cell viability. Using a live dead dye allows for the exclusion of dead cells when analyzing data. We illustrated the differences between ELISpot and flow cytometry by stimulating cells with two toll-like receptor (TLR) agonists, LPS or Pam3CSK4. Both activators increase production of various cytokines, including IL-10, IL-6, and TNF-alpha. The TLR2 antagonist, MMG-11, was used to inhibit this increased cytokine production. We observed some inhibition of IL-6 and IL-10 from Pam3CSK4 stimulation in the presence of MMG-11 by flow cytometry. TNF-α remains largely unchanged as its basal expression is high, but there is some reduction in the presence of MMG-11 for both methods. However, IL-10 was difficult to detect by ELISpot given the low seeding density. Overall, both ELISpot and flow cytometry are good methods for detecting secreted and intracellular cytokines, respectively, and should be used as complimentary assays.

Binding and detoxification efficiency of albumin decline after haemodialysis.

BACKGROUND: Albumin, as the most abundant plasma protein, represents a target structure for both drug and physicochemical therapeutic approaches to eliminate uraemic toxins more efficiently. Potentially, this approach could reduce mortality of haemodialysis patients. However, little is known about albumin functional properties in these patients and its alteration by haemodialysis treatment. METHODS: The binding and detoxification efficiency of albumin were assessed by electron paramagnetic resonance spectroscopy using a spin-labelled fatty acid. Binding efficiency (BE) reflects strength and amount of bound fatty acids under certain ethanol concentration. Detoxification efficiency (DTE) reflects the molecular flexibility of the patient's albumin molecule, thus the ability to change the conformation depending on ethanol concentration. Percentage of BE and DTE are depicted in relation to healthy individuals (100%). RESULTS: Fifty-eight patients (59% male, median age 68 years, median time on haemodialysis 32 months) were included in the study. Before haemodialysis treatment, albumin binding and detoxification efficiency were substantially below healthy individuals [median BE 52% (interquartile range, IQR, 45%-59%); median DTE 38% (IQR 32-49%)]. After haemodialysis treatment, median BE and DTE significantly decreased [BE 28% (IQR 20-41%); DTE 11% (IQR 7%-27%; P < .001)]. BE and DTE decline after haemodialysis was not dependent on age, sex or treatment modalities, but was to a certain extent on the level of non-esterified fatty acids. CONCLUSION: Albumin binding and detoxification efficiency of fatty acids in maintenance haemodialysis patients were substantially below those in healthy individuals and even declined after dialysis treatment. These findings might be helpful when considering new therapeutic approaches in maintenance haemodialysis patients.

Effect of serum creatinine difference between the Jaffe and the enzymatic method on kidney disease detection and staging.

Background: Serum creatinine (SCr), mainly determined by the Jaffe or an enzymatic method, is the central marker to assess kidney function. Deviations between these two methods may affect the diagnosis and staging of acute kidney injury (AKI) and chronic kidney disease (CKD). Methods: The results of the first parallel SCr measurement (Jaffe and enzymatic method) of adult in- and outpatients in the same serum sample at the University Hospital Essen (Essen, Germany) between 2020-2022 were retrospectively evaluated. A Bland-Altman plot with 95% limits of agreement (LoAs) was used to assess the difference between the Jaffe and the enzymatic SCr (eSCr) method. We used the 2009 Chronic Kidney Disease Epidemiology Collaboration equation for determination of estimated glomerular filtration rate (eGFR) according to the Kidney Disease: Improving Global Outcomes guidelines. Results: A total of 41 144 parallel SCr measurements were evaluated. On average, Jaffe SCr was 0.07 mg/dl higher than eSCr (LoA -0.12; 0.25 mg/dl). In 19% of all cases there was a different CKD stage when comparing eGFR between both SCr methods, of which 98% resulted in a more severe CKD stage determined with Jaffe SCr. In 1.6% of all cases Jaffe SCr was ≥0.3 mg/dl higher than eSCr. Conclusion: The present study showed that methods of SCr measurement may affect both the diagnosis and staging of AKI and CKD. This must be taken into account when interpreting measurements of renal function in everyday clinical practice, but also when planning and comparing studies on renal diseases. One should therefore stay with one method for SCr measurement, preferably with the enzymatic method.

Single-Nucleotide Polymorphism in Genes Encoding G Protein Subunits GNB3 and GNAQ Increase the Risk of Cardiovascular Morbidity among Patients Undergoing Renal Replacement Therapy.

Single-nucleotide polymorphisms in G protein subunits are linked to an increased risk of cardiovascular events among the general population. We assessed the effects of GNB3 c.825C > T, GNAQ -695/-694GC > TT, and GNAS c.393C > T polymorphisms on the risk of cardiovascular events among 454 patients undergoing renal replacement therapy. The patients were followed up for a median of 4.5 years after the initiation of dialysis. Carriers of the TT/TT genotype of GNAQ required stenting because of coronary artery stenosis (p = 0.0009) and developed cardiovascular events involving more than one organ system (p = 0.03) significantly earlier and more frequently than did the GC/TT or GC/GC genotypes. Multivariate analysis found that the TT/TT genotype of GNAQ was an independent risk factor for coronary artery stenosis requiring stent (hazard ratio, 4.5; p = 0.001), cardiovascular events (hazard ratio, 1.93; p = 0.04) and cardiovascular events affecting multiple organs (hazard ratio, 4.9; p = 0.03). In the subgroup of male patients left ventricular dilatation with abnormally increased LVEDD values occurred significantly more frequently in TT genotypes of GNB3 than in CT/CC genotypes (p = 0.007). Our findings suggest that male dialysis patients carrying the TT genotype of GNB3 are at higher risk of left ventricular dilatation and that dialysis patients carrying the TT/TT genotype of GNAQ are prone to coronary artery stenosis and severe cardiovascular events.

Albumin redox state of maintenance haemodialysis patients is positively altered after treatment.

BACKGROUND AND AIM: Maintenance haemodialysis patients have increased morbidity and mortality which is mainly driven by an elevated inflammation level due to the uraemic milieu. A major part of this increased inflammation level is the degree of oxidative stress which can be assessed by albumin redox state (ARS). Aim of this study was to evaluate how the ARS is affected by a haemodialysis treatment and different dialyzer properties. METHODS: ARS was determined before and after haemodialysis treatment by fractionating it into reduced human mercaptalbumin (HMA), reversibly oxidized human non-mercaptalbumin 1 (HNA-1), and irreversibly oxidized human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. In healthy individuals, albumin circulates in the following proportions: HMA 70-80%, HNA-1 20-30% and HNA-2 2-5%. High flux (FX 100 [Fresenius Medical Care], BG 1.8 [Toray], Xevonta Hi 18 [B. Braun], CTA-2000 [Kawasumi]) and low flux FX10 [Fresenius Medical Care] dialyzers were used. RESULTS: 58 patients (59% male, median age 68 years, median time on haemodialysis 32 month) were included in the study. Before haemodialysis treatment, HMA (median 55.9%, IQR 50.1-61.2%) was substantially lower than in healthy individuals. Accordingly, oxidized albumin fractions were above the level of healthy individuals (median HNA-1 38.5%, IQR 33.3-43.2%; median HNA-2 5.8%, IQR 5.1-6.7%). Before haemodialysis treatment HMA was significantly higher in patients usually treated with high flux membranes (p < 0.01). After haemodialysis treatment there was a significant increase of HMA and a decrease of HNA-1 and HNA-2 (p < 0.01). These effects were more pronounced in patients treated with high flux dialyzers (p < 0.01). There were no differences of ARS alteration with regard to the dialyzer´s sterilization mode or the presence of diabetes. CONCLUSION: The study confirms that the ARS is positively altered by haemodialysis and shows for the first time that this effect depends on dialyzer properties.

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients.

Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC p < 0.001, mDC1 p < 0.001, mDC2 p = 0.005) and increased numbers of IRF8-positive monocytes (p < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections (p = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.

[Staging of kidney disease today and tomorrow]. / Stadieneinteilung von Nierenkrankheiten heute und morgen.

Since September 2022, there is a new, German-language glossary for the nomenclature of renal function and renal disease, aligned with international technical terms and KDIGO guidelines for a more precise and uniform description of the facts. Terms such as "renal disease," "renal insufficiency," or "acute renal failure" should be avoided and replaced with "disease" or "functional impairment."The KDIGO guideline recommends in patients with CKD stage G3a, in addition to the determination of serum creatinine, the additional determination of cystatin to confirm the CKD stage. A combination of serum creatinine and cystatin C to estimate GFR without taking into account the so-called race coefficient seems to be more accurate in African Americans than the previous eGFR formulas. However, there is no recommendation on this in international guidelines yet. For Caucasians, the formula does not change.Renal function impairment lasting more than 7 days but less than 3 months is called acute kidney disease (AKD). The AKD stage is the critical time window for therapeutic interventions to reduce the risk of progression in kidney disease.A future, expanded AKI definition incorporating biomarkers will allow patients to be divided into subclasses according to functional and structural limitations, thus mapping the two-dimensionality of AKI. By using artificial intelligence, large amounts of data from clinical parameters, blood and urine samples, histopathological and molecular markers (including proteomics and metabolomics data) can be used integratively for the graduation of CKD and thus contribute significantly to individualized therapy.

Effect of intraoperative haemoadsorption therapy on cardiac surgery for active infective endocarditis with confirmed Staphylococcus aureus bacteraemia.

OBJECTIVES: Sepsis caused by infective endocarditis (IE), due to Staphylococcus aureus, is associated with significant morbidity and mortality. Blood purification using haemoadsorption (HA) may attenuate the inflammatory response. We investigated the effect of intraoperative HA on postoperative outcomes in S. aureus IE. METHODS: Patients with confirmed S. aureus IE undergoing cardiac surgery were included in a dual-centre study between January 2015 and March 2022. Patients treated with intraoperative HA (HA group) were compared to patients not treated with HA (control group). The primary outcome was vasoactive-inotropic score within the first 72 h postoperatively and secondary outcomes were sepsis-related mortality (SEPSIS-3 definition) and overall mortality at 30 and 90 days. RESULTS: No differences in baseline characteristics were observed between groups (haemoadsorption group, n = 75, control group, n = 55). Significantly decreased vasoactive-inotropic score was observed in the haemoadsorption group at all time points [6 h: 6.0 (0-17) vs 17 (3-47), P = 0.0014; 12 h: 2 (0-8.3) vs 5.9 (0-37), P = 0.0138; 24 h: 0 (0-5) vs 4.9 (0-23), P = 0.0064; 48 h: 0 (0-2.1) vs 0.1 (0-13), P = 0.0192; 72 h: 0 (0) vs 0 (0-5), P = 0.0014]. Importantly, sepsis-related mortality (8.0% vs 22.8%, P = 0.02) and 30-day (17.3% vs 32.7%, P = 0.03) and 90-day overall mortality (21.3% vs 40%, P = 0.03) were also significantly lower with haemoadsorption. CONCLUSIONS: Intraoperative HA during cardiac surgery for S. aureus IE was associated with significantly lower postoperative vasopressor and inotropic requirements and resulted in lower sepsis-related and overall 30- and 90-day mortality. In this high-risk population, improved postoperative haemodynamic stabilization by intraoperative HA appears to improve survival and should be further tested in future randomized trials.

Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura.

BACKGROUND: The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety. OBJECTIVES: This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting. METHODS: We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls). RESULTS: Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%. CONCLUSION: Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www. CLINICALTRIALS: gov as #NCT04985318.

COVID-19 associated acute transplant failure after AB0-incompatible living donor kidney transplantation - a case report.

INTRODUCTION: Immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0-incompatible living donor kidney transplantation. CASE PRESENTATION: A 34-year-old unvaccinated patient is diagnosed with SARS-CoV-2 infection four months after kidney transplantation. With only mild symptoms and an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m2, therapy with molnupiravir was initially given. Within the next eight weeks, transplant biopsies were performed for acute graft failure. These showed acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB), and borderline rejection (BANFF cat. 3). A therapy with prednisolone and intravenous immunoglobulins was performed twice. With unchanged graft failure, the third biopsy also formally showed BANFF cat. 4 IB. However, fluorescence in situ hybridization detected SARS-CoV-2 viruses in large portions of the distal tubules. After nine weeks of persistent COVID-19 disease neither anti-SARS-CoV-2 IgG nor a SARS-CoV-2-specific cellular immune response could be detected, leading to the administration of sotrovimab and remdesivir. Among them, SARS-CoV-2 clearance, detection of IgG, and improvement of graft function were achieved. CONCLUSION: Lack of viral clearance can lead to complications of SARS-CoV-2 infection with atypical manifestations. In kidney transplant patients, before initiating therapy, the differential diagnoses of "rejection" and "virus infection" should be weighed against each other in an interdisciplinary team of nephrologists, infectious diseases specialists and pathologists.

Phenotyping of M1 and M2a Macrophages and Differential Expression of ACE-2 on Monocytes by Flow Cytometry: Impact of Cell Culture Conditions and Sample Processing.

Macrophages are ubiquitously distributed throughout the various tissues of the body and perform many functions including the orchestration of inflammatory responses against pathogens by classically activated M1 macrophages and the regulation of wound healing and tissue remodeling by anti-inflammatory, alternatively activated M2 macrophages. The responsibility for these pleiotropic functions lies in the expression of a myriad of surface receptors unique to given subsets of macrophages. Much of what we know about the function of human macrophage subsets has been gleaned by studying in vitro generated macrophages matured in the presence of GM-CSF or M-CSF and polarized with different cytokines. Oftentimes, culture conditions, such as the type of serum used, the duration of the culture, and the use of polarizing cytokines, vary between studies making direct comparisons difficult. Sample preparation and processing (e.g., Ficoll® enrichment of leukocytes from whole blood) can also influence gene expression on human monocytes. Furthermore, overlap in surface marker expression can make it difficult to distinguish between different macrophage subsets.We directly compared the expression of over 20 different surface markers on M1 and M2a macrophages cultured in either serum-free media or in the presence of fetal bovine serum or human AB serum and found that the presence or type of serum used affected the expression of several markers such as CD200R1 and CD32. Moreover, we compared the expression of these surface markers on polarized and unpolarized macrophages and determined that polarization was critical to the expression of several of these markers including CD38 and SLAM F7. Differences in sample processing can alter the expression of surface markers, such as ACE-2, on monocytes. We observe that ACE-2 expression is higher on human whole blood CD14+ monocytes versus Ficoll®-enriched CD14+ monocytes derived from PBMCs (peripheral blood mononuclear cells), where expression can be reduced by up to 50%. These results indicate that differences in serum, culture media, and sample processing can alter gene expression in both human macrophages and monocytes. Importantly, the results of these studies significantly expand our knowledge of the phenotypic differences between human M1 and M2a macrophages and demonstrate the importance of culture conditions in generating these phenotypes.

Intraoperative hemoadsorption in high-risk patients with infective endocarditis.

BACKGROUND: Postoperative sepsis is an important cause of morbidity and mortality in patients with infective endocarditis undergoing surgical therapy. Blood purification using hemoadsorption therapy shows promising results in the treatment of sepsis. In this study, the clinical effects of intraoperative hemoadsorption in high-risk patients with infective endocarditis were evaluated. METHODS: Eligible candidates were high-risk patients with infective endocarditis undergoing cardiac surgery between January 2014 and December 2019. Patients with intraoperative hemoadsorption (hemoadsorption) were compared to patients without hemoadsorption (control). The endpoints were the incidence of postoperative sepsis, sepsis-associated death and in-hospital mortality. Additionally, postoperative vasopressor need, systemic vascular resistance indices and Sequential Organ Failure Assessment (SOFA) scores were compared. RESULTS: After propensity score matching, 70 high-risk patients were included. Postoperative sepsis occurred in 14 patients in the hemoadsorption group and in 16 patients in the control group, p = 0.629. Four patients died due to postoperative sepsis in the hemoadsorption group, while 11 postoperative septic patients died in the control group, p = 0.041. In-hospital mortality was 34% in the hemoadsorption group versus 43% in the control group, p = 0.461. On ICU-admission and the first postoperative day, the cumulative vasopressor need was 0.17 versus 0.25 µg/kgBW/min, p = 0.123 and 0.06 versus 0.11 µg/kgBW/min, p = 0.037, and the systemic vascular resistance index was 1448 versus 941 dyn·s·cm-5, p = 0.013 and 1156 versus 858 dyn·s·cm-5, p = 0.110 in the hemoadsorption versus control group, respectively. Postoperative course of SOFA score normalized significantly (p = 0.01) faster in the hemoadsorption group. CONCLUSIONS: In high-risk cardiac surgical patients with infective endocarditis, intraoperative hemoadsorption significantly reduced sepsis-associated mortality. Furthermore, intraoperative hemoadsorption resulted in significant faster recovery of hemodynamics and organ function. Intraoperative hemoadsorption seems to attenuate the severity of postoperative sepsis.

Severe and long-lasting alteration of albumin redox state by plasmapheresis.

Plasmapheresis (PE) is an established form of therapeutic apheresis (TA). Purpose of this longitudinal prospective single center study was to investigate the effect of PE on albumin redox state (ARS), as infusion of commercial albumin during PE may alter albumin oxidation which has an impact on its functional properties and oxidative stress level. 43 subjects with autoimmune-mediated neurological disorders were included. 20 subjects in the experimental group received five treatments of PE. 13 subjects received five treatments of immunoadsorption and 10 subjects received no TA as controls. ARS was determined before and after TA and 12 days after the last TA by fractionating it into human mercaptalbumin (HMA), human non-mercaptalbumin 1 (HNA-1), and human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. Irreversibly oxidised HNA-2 increased over the course of five PE treatments from 2.8% (IQR 1.3-3.7%) to 13.6% (IQR 10.9-15.9) (P < 0.01) and remained elevated 12 days after the last PE procedure (7.7% IQR 7.1-10.5, P < 0.05). The study showed for the first time that PE exerts a severe and long-lasting alteration on ARS indicating a new adverse effect of PE, that may influence oxidative stress level.

[Treatment and progression management of acute kidney injury]. / Behandlung und Progressionsbeeinflussung des akuten Nierenversagens.

Acute kidney injury (AKI) represents one of the greatest global health challenges and is associated with high mortality. The often multifactorial etiology and complex pathophysiological mechanisms have so far hampered the development of causal therapeutic options. The treatment should be stage-adapted according to the current KDIGO guideline: avoid nephrotoxicity, optimize volume status and perfusion pressure, monitor serum creatinine, urine output and proteinuria. New insights into the influence of mitochondrial dysfunction and cellular senescence in AKI, well-defined study endpoints, and innovations through nanotechnology may enable targeted drug-based AKI therapy in the future. Especially the weeks following an AKI are a vulnerable phase and crucial for progression management.

Early Treatment with Monoclonal Antibodies or Convalescent Plasma Reduces Mortality in Non-Vaccinated COVID-19 High-Risk Patients.

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants.

Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients.

BACKGROUND: Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. METHODS: In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. RESULTS: The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P  = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P  = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P < 0.0001). Furthermore, thromboelastometry showed fibrinolysis shutdown among COVID-19 patients with significantly lower maximum of lysis than among sepsis patients (EXTEM: 0.6 ± 1.2 % vs. 3.3 ± 3.7 %; P  = 0.013). Seven of 20 COVID-19 patients experienced thromboembolic events, whereas no patient in the sepsis group experienced such events. CONCLUSIONS: ROTEM analysis showed significantly different pathological findings characterized by hypercoagulability and fibrinolysis shutdown among COVID-19 patients with a severe disease course compared to patients with severe sepsis. These abnormalities seem to be associated with thromboembolic events.

Extracorporeal cytokine adsorption: Significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery.

BACKGROUND: Extracorporeal cytokine adsorption is an option in septic shock as an additional measure to treat a pathological immune response. Purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamic parameters in patients with acute kidney injury (AKI) on continuous renal replacement therapy (CRRT) and septic shock after cardiac surgery. METHODS: In this retrospective study, a total of 98 patients were evaluated. Hemoadsorption was performed by the CytoSorb® adsorber. In all patients cytokine adsorption was applied for at least 15 hours and at least one adsorber was used per patient. To compare cumulative inotrope need in order to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg, we applied vasoactive score (VAS) for each patient before and after cytokine adsorption. A paired t-test has been performed to determine statistical significance. RESULTS: Before cytokine adsorption the mean VAS was 56.7 points. This was statistically significant decreased after cytokine adsorption (27.7 points, p< 0.0001). Before cytokine adsorption, the mean noradrenalin dose to reach a MAP of ≥ 65 mmHg was 0.49 µg/kg bw/min, the mean adrenalin dose was 0.12 µg/kg bw/min. After cytokine adsorption, significantly reduced catecholamine doses were necessary to maintain a MAP of ≥ 65 mmHg (0.24 µg/kg bw/min noradrenalin; p< 0.0001 and 0.07 µg/kg bw/min adrenalin; p < 0.0001). Moreover, there was a significant reduction of serum lactate levels after treatment (p< 0.0001). The mean SOFA-score for these patients with septic shock and AKI before cytokine adsorption was 16.7 points, the mean APACHE II-score was 30.2 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.7 points was 77,0%, respectively 73,0% on APACHE II-score, while the all-cause in-hospital mortality rate of the patients in this study was 59.2%. CONCLUSION: In patients with septic shock and AKI undergoing cardiac surgery, extracorporeal cytokine adsorption could significantly lower the need for postoperative inotropes. Additionally, observed versus SOFA- and APACHE II-score predicted in-hospital mortality rate was decreased.