Freitag, 02.10.2020

14:00 - 15:30

Poster DGfN 2020

Covid-19 1 (P035 - P044; LA08 - LA11)

 
How hemodialysis patients perceive the corona virus crisis
P035 

T. Davidovic, H. Sprenger-Mähr, A. Abbassi-Nik, E. Zitt, K. Lhotta; Feldkirch/A

Objective: The ongoing coronavirus pandemic forced many countries to implement strict and unprecedented precautions to stop the spread of the virus. On top of these measures, hemodialysis units have adopted their own rules to protect wards and patients from Covid-19. Little is known on how these measures are perceived by hemodialysis patients.
Method: The study was performed in the three hemodialysis units in Vorarlberg, the westernmost province of Austria. A questionnaire was developed consisting of 22 questions on how patients felt affected by the crisis and the general measures and by specific precautions implemented on dialysis wards. All adult patients were asked to fill out the questionnaire anonymously.
Results: Out of 202 hemodialysis patient 148 answered the the questionnaire (66.9% males, mean age 68.3±13.3 years). The vast majority (83.1%) were worried by the corona crisis and 28.4% reported a negative impact on emotional wellbeing. Their daily life was most affected by the general ban on visits (58.6%) and home confinement (35.9%). 75% of patients feared to contract Covid-19, 33.3% were afraid of economic consequences, and 16.7% of loneliness and isolation. The safety measures on dialysis wards were classified as sufficient by 97.3%. 78.2% of patients felt safe during dialysis treatment. All dialysis-specific precautions (individual transport, health check, hand desinfection, wearing a face mask and physical distancing) were rated as important or very important by almost all patients. Non of the patients acquired SARS-CoV-2 infection up to now.
Conclusion: Although the coronavirus crisis worried and affected the daily life of most hemodialysis patients, the effect on emotional wellbeing was moderate. Patients felt safe on dialysis wards and acceptance of specific precautions was high.

 
Renin-Angiotensin-Aldosterone-System Blocking Drugs in Patients with SARS-CoV-2 - Systematic Review and Meta-Analysis
P036 

C. Chu, S. Zeng, A. Hasan, C.-F. Hocher, B. K. Krämer, B. Hocher; Berlin, Potsdam, Mannheim

Objective: COVID-19 patients treated with RAAS blockers are among the patients at highest risk of poor outcome. ACE2 is the functional receptor for SARS-CoV-2. Animal studies suggest that RAAS blockers might increase the expression of ACE2 and potentially increase the risk of SARS-Cov-2 infection.

P036


Method: We conducted a systematic review and meta-analysis of published studies on the association of RASS blocking agents with lung disease related outcomes.
Results: The effect of ACE inhibitor treatment on the incidence of pneumonia in non-COVID-19 patients was analyzed in 25 studies (330,780 patients). ACE inhibitor use was associated with a 27% reduction of pneumonia risk (OR: 0.73, p<0.001). Pneumonia related death cases in ACE inhibitor treated non-COVID-19 patients were reduced by 27% (OR: 0.73, p=0.004). ARB treatment was analyzed in 10 studies (275,621 non-COVID-19 patients). The risk of pneumonia was not different between patients who did or did not use ARBs. Pooled result from 13 studies (27,704 COVID-19 patients) showed that COVID-19 related server adverse clinical outcomes were not different between patients who did or did not use RAAS blocking agents (OR: 0.87, p=0.28). All-cause mortality risk in COVID-19 patients was reduced by 27% (p=0.04).
Conclusion: Given the weak evidence coming from animal studies and the clear beneficial data of ACE inhibition in non-COVID-19 patients and the limited but promising data in COVID-19 patients, the use of RAAS blocking agents in patients with SARS-CoV-2 infection is justified. Further clinical studies analysing ARBs and ACE inhibitors separately in COVID-19 patients are needed.

 
Bevorzugte Antikoagulation für Nierenersatzverfahren auf der Intensivstation im Rahmen COVID-19 assoziierter Hyperkoagulabilität.
P037 

F. Arnold, L. Westermann, S. Rieg, E. Neumann-Haefelin, P. Biever, G. Walz, J. Kalbhenn, Y. Tanriver; Freiburg

Hintergrund: Die aktuelle COVID-19-Pandemie ist auch für Nephrologen eine große Herausforderung. Eine Infektion mit SARS-CoV2 erhöht das Risiko für akutes Nierenversagen (ANV) maßgeblich und notwendige kontinuierliche Nierenersatzverfahren werden durch eine Virus-assoziierte Hyperkoagulabilität erschwert. Thrombosierungen im extrakorporalen Kreislauf erfordern häufig eine frühzeitige Beendigung des Verfahrens. Dies reduziert die Dialysequalität, erhöht Blutverluste und kann Komplikationen begünstigen.
In unserer Studie vergleichen wir daher verschiedene Antikoagulationsstrategien um geeignete Regime zu identifizieren.
Methode: Retrospektive Single-Center-Beobachtungsstudie an 71 intensivmedizinisch behandelten COVID-19 Patienten an einem universitären Zentrum der Maximalversorgung in Deutschland.
Ergebnisse: Von 71 schwer an COVID-19 erkrankten Patienten erlitten 53 (75%) ein ANV, 23 (32%) wurden mit kontinuierlichen Dialyseverfahren therapiert.
Im Rahmen kontinuierlicher Dialyseverfahren (CVVHD) erhielten 7 Patienten (Verfahren n=13) unfraktioniertes Heparin (UFH), bei 18 Patienten (n=92) kam eine regionale Citratantikoagulation zum Einsatz. Die mittlere Dauer je Behandlung betrug in der UFH-Gruppe 21,13h (SEM: ±5,60h) und in der Citrat-Gruppe 45,57h (SEM: ±2,67h). Die Differenz von 24,44h war signifikant (p=0,0014).
Im Rahmen von SLEDD (sustained low-efficiency daily dialysis)-Verfahren erhielten 9 Patienten (n=22) UFH, 3 Patienten (n=27) Argatroban und 7 Patienten (n=71) subkutan appliziertes niedermolekulares Heparin (LMWH). Die mittlere Dauer je Behandlung betrug in der UFH-Gruppe 8,14h (SEM: ±1,33h), in der Argatroban-Gruppe 7,99h (SEM: ±0,90h) und in der LMWH-Gruppe 11,66h (SEM: ±0,57h). Die Differenzen zur LMWH-Gruppe von 3,52h respektive 3,67h waren signifikant (p=0,0047/p=0,0138).
Zusammenfassung: Die Daten zeigen, dass bei CVVHD-Verfahren eine regionale Antikoagulation mit Citrat und bei SLEDD-Verfahren niedermolekulares Heparin überlegene Antikoagulationsstrategien bei COVID-19 assoziierter Hyperkoagulabilität sind. Sie reduzieren das Risiko einer frühzeitigen Beendigung des Verfahrens durch Thrombosierung im extrakorporalen Kreislauf signifikant. Diese Antikoagulationsstrategien können zu einer besseren Dialysequalität beitragen und Risiken durch häufige Dialysesystemwechsel verringern. Sie reduzieren überdies Personalaufwand und schonen kritische Ressourcen, was in Anbetracht der aktuellen und möglicher zukünftiger Pandemien besondere Bedeutung hat.

 
Complement activation in renal biopsies from patients with COVID-19 infection
P038 

F. Pfister, E. Vonbrunn, C. Daniel, M. Büttner-Herold, K. Amann; Erlangen

Objective: Most patients who become criticically ill following infection with COVID-19 develop acute respiratory distress syndrome (ARDS) which has been atributed to a maladaptive or inadequate immune response. Complement is an important component of the innate immune response that is involved in opsonisation of viruses but also in triggering other immune cells. Complement can be activated via 3 different cascades: (i) the classical, (ii) the alternate and (iii) the lectin pathway. Apart from the lung, the kidney is the second most common organ affected by COVID-19. Therefore, we investigated the involvement of the complement system in renal biopsies of COVID-19 patients.
Method: We investigated 5 kidney biopsies from renal transplants and 2 kidneys from autopsy material from COVID-19 infected patients. Renal tissue was analyzed for signs of renal injury and complement activation was detected by immunehistochemical staining for C1q, MASP-2, C3c and C5b9. Furthermore, platelets were detected by CD61 staining and infection of renal cells by COVID-19 was detected by insitu hybridization (RNAscope). Biopsies fom patients with hemolytic uremic syndrome (HUS, n=4), sepsis (n=3), zero-biopsies with disseminated intravascular coagulation (DIC, n=7) and zero-biopsies from living donors (n=6) served as controls.
Results: Covid-19 was detected in all renal tissues from COVID-19 patients in varying numbers, with focal localisation in endothelial and tubular cells. The highest frequency of CD61-positive platelets was detected in peritubular capillaries and arteries from COVID-19 infected renal biopsies compared to all controls. Fibrin thrombi in capillaries colocalized with MASP-2, the activator of the lectin-mediated complement pathway. Apart from COVID-19 biopsies, MASP-2 could only be detected in glomeruli with DIC. In contrast, the classical complement activation pathway (i.e. C1q) was hardly present in COVID-19 biopsies. C3c, the common marker of all three complement activation pathways was detected in renal arteries.  Prominent C5b9 deposition as part of the complement termnal membrane attac complex was detected in COVID-19 biopsies predominantly in renal arterioles and the glomerular hilus region while capillary C5b9 deposition was lower and also occured in controls.
Conclusion: Complement activation of the lectin-pathway was present in kidneys from COVID-19 patients and might be involved in worsening of renal injury. Specific complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury.

 
Psychological responses to the Covid-19 pandemic in renal transplant recipients
P039 

P. Zgoura, A. Doevelaar, C. Waldecker, F. Seibert, A. Wunsch, P. Schenker, F. Bauer, B. Rohn, R. Viebahn, N. Babel, T. H. Westhoff; Herne, Bochum

Objective: With regard to immunosuppression and the high level of cardiovascular comorbidity renal transplant recipients are supposed to be at substantially increased risk for an adverse course of Covid-19. To date, there are no data on the psychological effects of this knowledge on renal transplant recipients during the pandemic.
Method: Cross sectional study on 62 renal transplant recipients and 30 nephrological patients without immunosuppression, who served as control. The study aimed at an assessment of anxiety, mood, and quality of life during the pandemic (April 2020) and six months before. The analysis was performed by means of a questionnaire derived from KPD-38. The questionnaire encompassed 38 questions on 6 parameters. We evaluated two parameters, life satisfaction and competence to act. Statistical analysis was performed using the Wilcoxon Test for the intragroup comparison of the two timepoints and the Mann-Whitney U test for intergroup comparisons
Results: The group of renal transplant recipients reached 336 (66.5%) of 500 maximum reachable points scoring for life satisfaction within the Covid-19 pandemic whereas 396 (78.5%) points have been attained before. In the control group we noticed 240 (7.4%) versus 200 (83.3%) of 240 reachable points in maximum. Recording to the parameter “competence to act” 787 (63.5%) of 1240 reachable points were achieved in the renal transplant recipient group during the pandemic and 910 (73.4%) 6 months before. During the pandemic the control group achieved 399 (66.5%) of 600 reachable points vs. 441 (73.5%) 6 months before.
Conclusion: Life satisfaction and competence to act were significantly reduced by the Covid-19 pandemic in the group of renal transplant recipients. Although we observed similar effects in the control group, differences in the scores were not that high. Being aware of this psychological impairment we should adjust patient care in threatening situations.

 
Low Seroprevalence of SARS-CoV-2 Antibodies during Systematic Screening for COVID-19 Infection in a German Cohort of Kidney Transplant Recipients
P040 

M. Choi, F. Bachmann, M. Naik, B. Zukunft, M. Dürr, W. Düttmann, T. Schwarz, V. Corman, L. Liefeldt, K. Budde, F. Halleck; Berlin

Objective: The COVID-19 pandemic caused by SARS-CoV-2 is affecting nearly every country and denotes a global health issue. Despite groups like old, immunocompromised or chronic diseased patients being at high risk, data regarding incidence in kidney transplant recipients (KTR) are sparse.
Method: From March 19th to May 19th we performed a systematic screening for COVID-19 from KTR. Tests included serum analysis for SARS-CoV-2 antibody tests using S protein–based immunofluorescence and anti-SARS-CoV-2 S1 IgG and IgA ELISAs and/or qRT-PCR from nasal-throat swabs. Serum samples were taken at outpatient visits and from KTR with PCR-confirmed COVID-19. Swab samples were derived from recipients (+donor) right before undergoing renal transplantation.
Results: Overall 342 patients were examined for recent or previous COVID-19 infection. We obtained serum samples from 223 patients, from which 62 patients were symptomatic in the past with upper airway symptoms (N=46), diarrhea (N=3), and/or other unspecific complaints (N=13). From these we identified 13 KTR (5.8%) with solely positive anti-SARS-CoV-2-IgA and 3 (1.3%) with both positive anti-IgA and anti-IgG. Using immunofluorescence analysis in addition, recent COVID-19 infection remained highly suspicious for 2 KTR. All 27 swab tests taken prior to transplantation (from 19 deceased-donor recipients and 4 live-donor recipient pairs) were negative. Outside from outpatient visits 5 out of 2,044 KTR from our follow-up program were symptomatic and tested COVID-19 positive by PCR, 4/5 patients recovered, one died. All patients showed seroconversion of IgA and IgG during the course of disease.
Conclusion: Using systematic serologic screening for the prevalence of COVID-19 infection we could demonstrate a low seroprevalence in a representative cohort of renal transplant patients. Effective containment strategies including face masks for source control, social distancing, hygienic education, doctor to patient distancing and implementation of telemedical services very likely accounted to the fact that numbers of COVID-19 infections were low and enabled us to continue our transplant program. Moreover, seroconversion with positive SARS-CoV-2 antibodies in KTR after CODIV-19 could be confirmed.

 
Plasma exchange in critically ill COVID-19 patients
P041 

C. Morath, M. Weigand, M. Zeier, C. Speer, T. Hippchen, S. Tiwari-Heckler, U. Merle; Heidelberg

Objective: The spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to respiratory failure and death of patients. Severely affected patients may develop a cytokine storm-like clinical syndrome with multi-organ failure and a mortality rate of up to 90%. Recently it has been suggested that plasma exchange (PE) may positively influence this unfavorable course.
Method: Here we report on five COVID-19 patients with a median age of 67 years who were treated at the intensive care unit due to respiratory failure. Prophylactic antibiotic, antimycotic, and antiviral/immunomodulatory therapy was initiated in all patients upon admission. During the course of the disease, patients developed circulatory shock and persistent fever together with increased interleukin 6-levels compatible with the cytokine storm-like clinical syndrome. In addition, all patients had multi-organ failure with acute respiratory-distress syndrome (ARDS, 4 severe, 1 moderate) and acute kidney injury of at least KDIGO stage 2.
Results: A single PE with a median of 3.39 L of fresh frozen plasma was initiated in all patients followed by one additional treatment in patients 1, 3, and 5. During the PE, striking reduction of inflammatory markers C-reactive protein (-47%, P=0.0078) and interleukin 6 (-74%, P=0.0078), as well as significant reduction of ferritin (-49%, P=0.0078), LDH (-41%, P=0.0078), and D-Dimer (-47%, P=0.016) were observed (Figure 1A-E).

P041

Due to circulatory shock, four patients received vasopressor treatment at the start of the PE that could be substantially reduced during treatment (-71%, P=0.031, Figure 1H). Biochemical and clinical improvement continued over the following days together with an increase in the oxygenation index in 4 out of 5 patients (Figure 1I). These improvements were achieved with only 1 to 2 PE, which might be a possible indication of a direct pathophysiological influence of PE on the COVID-19-associated cytokine storm-like clinical syndrome. Three of the 5 most critically ill patients are alive, while a 71-year-old male and a 76-year-old female patient died after the therapy was limited due to persistent severe ARDS.
Conclusion: It has been suggested that a cytokine storm-like clinical syndrome may be responsible for a significant proportion of COVID-19-associated patient deaths. PE improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes. Further studies to test whether (repeated) PE can alter the course of critically ill COVID-19 patients are clearly indicated.

 
Transplant patients are able to mount SARS-CoV2-reactive T-cell response with the magnitude and functionality comparable to non-immunosuppressed patients
P042 

N. Babel, M. Anft, A. Blazquez-Navarro, K. Paniskaki, A. Doevelaar, F. Seibert, B. Hoelzer, C. Thieme, M. Konik, T. Brenner, S. Dolff, T. Roch, O. Witzke, U. Stervbo, T. H. Westhoff, R. Viebahn; Herne, Essen, Berlin, Bochum

Objective: The optimal management of COVID-19 in transplant patients is not defined so far. The major concern is the ability of transplant patients to generate a sufficient antiviral response under immunosuppressive treatment.
Method: Here, we analysed T-cell immunity directed against Spike, Membrane and Nucleocapsid proteins of SARS-CoV-2 in a small cohort of 6 transplant patients (TP) with COVID-19 in comparison to 28 non-immunousppressed patients (NIP).
Results: The median patient age of transplant cohort (3 renal transplant, 1 lung, and 1 compbined liver-kidney and 1 pancreas-kidney) as well as gender did not differ from NIP. We also did not find statistical differences for the time between the diagnosis of COVID-19 and analysis of T-cell immunity between the two cohorts. Notalby, despite immunosuppressive therapy, we were able to detect a strong antiviral response in transplant patients. TP generated SARS-CoV-2 reactive T-cells against all three proteins with predominance of CD4+ T cells with pro-inflammatory Th1 phenotype. Moreover, SARS-CoV-2 reactive CD4+ and CD8+ T cells were able to produce multiple pro-inflammatory cytokines demonstrating their potential protective capacity. Of interest, the frequencies and cytokine production patterns of SARS-CoV-2 reactive T-cells did not show any differences between TP and NIP.
Conclusion: A strong polyfunctional T-cell response directed against all three SARS-CoV-2 proteins can be generated in transplant despite immunousppressive treatment. In comparison to non-immunosuppressed patients, the antiviral immunity is non-inferior. Since the dosage of immunosuppression in analysed patients was reduced, further studies are required to assess the antiviral immunity under standard immunosuppression.

 
Kidney findings in COVID-19 patients – results of a comprehensive autopsy study on 21 cases
P043 

T. Menter, J. Haslbauer, K. Mertz, M. Herzig, A. Tzankov, H. Hopfer; Basel/CH, Liestal/CH

Objective: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly evolved into an extensive worldwide pandemic. SARS-CoV-2 does not only affect the lungs but is rather a systemic disease with pathologies in various organ systems particularly in the kidneys. In fact, acute kidney injury in COVID-19-patients is a risk factor for poor outcome.
Method: In order to provide insight into morphologic changes of the kidneys in COVID-19patients, we examined specimens of 21 autopsies by conventional histology and immunohistochemistry. Selected cases were further investigated by electron microscopy and presence of viral RNA was tested throughout by qPCR.
Results: Acute kidney injury manifesting as acute tubular damage and interstitial edema was present in most patients. There was no evidence of glomerulonephritis or virally induced acute interstitial nephritis in any case. Focal signs of thrombotic microangiopathy interpreted as manifestations of disseminated intravascular coagulation were seen in three cases. Several kidneys showed chronic changes attributable to hypertensive and/or diabetic nephropathy. By electron microscopy, virus-like particles confined to small vesicles could be detected in tubular epithelial cells. The rate of acute or acute-on-chronic renal failure was high in our cohort both at the time of hospital admission and during hospitalization (12/18 and 14/18 patients with available data, respectively).
Conclusion: Kidneys are affected by COVID-19, which primarily manifests as acute tubular injury in the majority of patients. This finding is unspecific and might be due to many different causes including generalized systemic inflammatory reaction, shock or hypoxia. However, we provide evidence for the presence of SARS-CoV-2 in the kidney itself which could serve as an argument for possible direct involvement of the virus in the pathogenesis of acute tubular injury. However, the virus does not seem to induce an inflammatory reaction in the kidney. Further studies are warranted to improve our understanding of renal pathophysiology in COVID-19.

 
coviki.org : The really good ideas and the scientific record on Covid-19 viral disease.
P044 

O. Groth; Zerbst/Anhalt

Objective: coviki.org collects citations of the peer-reviewed literature on covid-19 disease and additional sources from news, predators and social media to keep the record of our knowledge, to fast-access knowledge on a given concept and to highlight unanticipated data on any related topic. coviki.org serves the individual clinician, the individual scientist but it is basically intended to give public health leaders hints on policy-changing developments and ideas. coviki.org is intended to give a indexing platform to the unproven hypotheses years before experimental validation and commercial exploitation. Database URL: http://www.coviki.org
Method: With old methods from my metatextbook of medicine available at www.moremed.org and using a wikimedia content management system for more sophisticated deep indexing, the db PubMed and PMCentral has been accessed on May 8th on term (covid19 OR covid-19 OR covid19 OR sars-cov2 OR sars-cov-2 OR 2019-ncov OR 2019ncov). A draft contents index has been set up and optimized with more data streaming in. Any valid on-topic paper is to be included. Very important papers are highlighted in the 'Unproven Ideas' section.

P044


Results: About 60 main categories with about 8000 papers are available to speed up individual learning. Subcategorization is in process intending to put the nephrology and pregnancy topics into a higher resolution. Most impact topic is Pathobiology with hints on Dysendotheliosis as a unifying concept for any organ manifestations of covid or general nosology of the systems diseases.
Conclusion: coviki.org is the basic resource to use to get into covid and to stay tuned on the unknown hypotheses. it is a superspreader for pre-clinical and pre-investigational ideas to feed those people wo run and control health systems and those engaged in drug development.
I felt a need of that kind of essential resource as I got the idea to look into magnesium and to tell others to look at this personal hit, I contacted anybody with absolutely no response.

 
Course and management of the Covid-19 pandemic in a German dialysis network
LA08 

Objective: Die globale Covid-19 Pandemie traf eine breitere Dialysepopulation in einer angeschlossenen Dialyseeinrichtung der Heinsberger Region. Wir beschreiben hier das Management der Erkrankung in einem größeren Dialysenetzwerk.
Method: Es wurde umgehend ein Triage-System für alle 65 beteiligten Dialyseeinrichtungen eingeführt, um den Betrieb der Dialyseeinrichtungen zu ermöglichen:

Klasse Maßnahmen
A Patienten mit bestätigter Covid-19 Infektion sowie schweren klinischen Symptomen sind umgehend stationär einzuweisen, weitere Dialysen finden im stationären Bereich statt.
B Patienten mit bestätigter Covid-19 Infektion und milden oder fehlenden klinischen Symptomen werden in ihrer Dialyseeinrichtung dialysiert jedoch in isolierter Umgebung bis eine zweifache Negativtestung vorliegt. Parallel ist eine private Quarantäne einzuhalten.
C Patienten mit Symptomen und ausstehendem Abstrichergebnis werden in separierten Räumen dialysiert bis das Ergebnis vorliegt. Die weitere Klassifikation eines Patienten richtet sich nach dem Ergebnis. Eine private Quarantäne ist einzuhalten.
D Patienten ohne Symptome und / oder negative Abstrichergebnis aber mit Kontakt zu Personen mit bestätigter Covid-19 Infektion werden nach Möglichkeit für 14 Tage in separaten Räumen dialysiert. Eine private Quarantäne ist einzuhalten.
0 Patienten ohne Kontakt zu infizierten Personen, ohne Symptome und ohne Abstrich bzw. negativem Abstrichergebnis werden in separaten Räumen dialysiert.

Nach Rückgang der initial bundesweit hohen Infektionszahlen wurde ein Ampel-System eingeführt, das Eskalationsstufen von Hygienemaßnahmen in angeschlossenen Praxen regelt
Results: Ein Ausdehnen des lokalen Infektionsgeschehens innerhalb der Einrichtungen konnte verhindert werden. Das eingeführte Ampelsystem konnte einzelne Covid-19 positive Patienten identifizieren und trägt somit zur frühen Identifikation von Covid-19 positiven Patienten sowie zur Eindämmung der Pandemie bei. Insgesamt konnte innerhalb des Netzwerks so das Infektionsgeschehen Seit Mai 2020 auf sporadische Fälle begrenzt gehalten werden.
Conclusion: Das geschilderte Management mit einer Kombination aus Hygienemaßnahmen und lokalem Patientenmanagement hat sich in einem größeren Dialysenetzwerk bewährt und stellt nach unserer Ansicht ein adäquates Umgehen mit der Covid-19 Pandemie dar.

 
Recovery from Acute Kidney Injury in COVID-19 patients
LA09 

H. Stockmann, J.-H. Hardenberg, A. Aigner, C. Hinze, I. Gotthardt, K.-U. Eckardt, K. M. Schmidt-Ott, P. Enghard; Berlin

Objective: Acute kidney injury (AKI) represents a frequent complication of severe COVID-19 disease with many patients requiring kidney replacement therapy (KRT). While the in-hospital mortality of these patients is high, little is known about the renal prognosis of survivors. AKI survivors in general are known to be at increased risk for chronic kidney disease (CKD) and end stage kidney disease (ESKD). Lack of resolution of AKI on hospital discharge is known to be a risk factor for adverse outcomes. Data on renal outcome after COVID-associated AKI are currently not available.

Method: We conducted a retrospective analysis of 77 COVID-19 patients with Stage 3 AKI according to the “Kidney Disease: Improving Global Outcomes” (KDIGO) classification, who were treated at three tertiary care hospitals between March 1st and June 3rd, 2020. Patients were followed up until August 18th, 2020 for death, kidney function upon discharge from the hospital, duration of AKI, and degree of renal recovery.

Results: Of 77 patients with Stage 3 AKI 96.1% required KRT. All patients were treated in intensive care units at the time of AKI Stage 3 onset. As of August 18th, five (6.5%) patients continued to be in the intensive care unit, 35 (45.5%) were deceased, and 37 (48.1%) had been discharged from the hospital. No patient had rapid reversal of AKI Stage 3, as defined by resolution below Stage 3 within 48 hours. The majority of patients (n=58, 75.3%) had AKI Stage 3 lasting ≥ 7 days. On hospital discharge, 23 patients (29.9%) had full renal recovery (resolution to no AKI). Partial recovery (resolution to AKI stage 1 or 2) upon hospital discharge was reached by another seven patients (9%). Seven patients (9%) had ongoing KRT upon hospital discharge. As of August 18th, 2020, 27 patients (35,1% of all AKI 3 patients, 73% of all discharged patients) had full renal recovery. The median time to full resolution of AKI in all patients was 23 days (IQR 11-50). The median duration of AKI Stage 3 was 16 days (IQR 7-39). The longest duration of AKI stage 3 before full resolution was 103 days.

Conclusion: Severe AKI in COVID-19 patients is associated with high in-hospital mortality. However, in surviving patients, full renal recovery is common even after a long course of dialysis dependency.

 
COVID-19-assoziierte akute Nierenschädigung ist assoziiert mit schwerem Krankheitsverlauf und systemischer Inflammation
LA10 

J.-H. Hardenberg, H. Stockmann, A. Aigner, P. Enghard, C. Hinze, I. Gotthardt, K.-U. Eckardt, K. M. Schmidt-Ott; Berlin

Hintergrund: Eine akute Nierenschädigung (acute kidney injury, AKI) stellt eine schwere Komplikation in COVID-19 dar. Allerdings sind die Epidemiologie und Pathophysiologie von COVID-19-assoziiertem AKI unvollständig verstanden. Ziel dieser Studie ist es, durch eine detaillierte Analyse klinischer Patientencharakteristika, ein besseres Verständnis für die Entwicklung eines COVID-assoziierten AKI zu erlangen.
Methode: Dies ist eine retrospektive Kohortenstudie an 223 konsekutiven COVID-19-Patienten, die in drei Kliniken der Maximalversorgung betreut wurden. Detaillierte demographische und klinische Baseline-Charakteristika sowie longitudinale Labor- und klinische Parameter wurden erhoben. AKI wurde entsprechend der „Kidney Disease: Improving Global Outcomes“ (KDIGO)-Klassifikation definiert und nach Schweregrad graduiert. Um klinische Parameter und Laborparameter zu identifizieren, welche unabhängig mit der Entwicklung eines schweren AKI (definiert als KDIGO Stadium 3) assoziiert sind, wurde eine multivariable Cox-Regression mit zeitabhängigen Kovariaten durchgeführt.
Ergebnisse: Von 117 Patienten (52,4%), die ein AKI entwickelten, hatten 70 Patienten (31%) ein schweres AKI. Patienten mit schwerem AKI waren älter, überwiegend männlich, hatten mehr Komorbiditäten und wiesen eine höhere Mortalität auf. Ein schweres AKI trat fast ausschließlich in Patienten auf der Intensivstation auf. 97,3% der Patienten mit schwerem AKI waren respiratorisch insuffizient, 95,7% waren dialysepflichtig. Invasive Beatmung, Katecholamintherapie und Entzündungsparameter (Procalcitonin und Leukozytenzahl) waren unabhängige Risikofaktoren für die Entwicklung eines schweren AKI. Es zeigte sich ein enger zeitlicher Zusammengang zwischen ansteigenden Entzündungsparametern und der Entwicklung von schwerem AKI.
Zusammenfassung: Die Entwicklung eines schweren AKI bei COVID-19-Patienten ist eng mit Krankheitsschwere und systemischer Entzündung assoziiert und entwickelt sich nicht als isolierte Organkomplikation.

 
COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTP
LA11 

A. Doevelaar, M. Bachmann, B. Hoelzer, F. S. Seibert, B. Rohn, F. Bauer, O. Witzke, U. Dittmer, M. Bachmann, S. Yilmaz, R. Dittmer, S. Schneppenheim, N. Babel, U. Budde, T. H. Westhoff; Herne, Hamburg, Essen, East Lansing/USA

Objective: Thrombotic microangiopathy (TMA) has been repeatedly described in COVID-19 and may contribute to SARS-CoV-2 associated hypercoagulability. The underlying mechanisms remain elusive. We hypothesized that endothelial damage may lead to substantially increased concentrations of Von Willebrand Factor (VWF) with subsequent relative deficiency of ADAMTS13.
Method: A prospective controlled trial was performed on 75 patients with COVID-19 of mild to critical severity and 10 healthy controls. VWF antigen (VWF:Ag), ADAMTS13 and VWF multimer formation were analyzed in a German hemostaseologic laboratory.
Results: VWF:Ag was 4.8 times higher in COVID-19 patients compared to healthy controls (p<0.0001), whereas ADAMTS13 activities were not significantly different (p=0.24). The ADAMTS13/VWF:Ag ratio was significantly lower in COVID-19 than in the control group (24.4±20.5 vs. 79.7±33.2, p<0.0001). Fourteen patients (18.7%) undercut a critical ratio of 10 as described in thrombotic thrombocytopenic purpura (TTP). Gel analysis of multimers resembled the TTP constellation with loss of the largest multimers in 75% and a smeary triplet pattern in 39% of the patients. The ADAMTS13/VWF:Ag ratio decreased continuously from mild to critical disease (ANOVA p=0.026). Moreover, it differed significantly between surviving patients and those who died from COVID-19 (p=0.001) yielding an AUC of 0.232 in ROC curve analysis.
Conclusion: COVID-19 is associated with a substantial increase in VWF levels, which can exceed the ADAMTS13 processing capacity resulting in the formation of large VWF multimers identical to TTP. The ADAMTS13/VWF:Ag ratio is an independent predictor of severity of disease and mortality. These findings render further support to perform studies on the use of plasma exchange in COVID-19 and to include VWF and ADAMTS13 in the diagnostic workup.

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