MODERATORS: Luuk Hilbrands, NL – Ron Gansevoort, NL

Kidney replacement therapy in the ICU in patients with COVID-19: treatment considerations.
PRESENTER: Claudio Ronco, IT
PANELLIST:   Casper Franssen, NL

How to prevent transmission in your dialysis unit?
PRESENTER: Rita S. Suri, CAN
PANELLIST:   Mario Cozzolino, IT

e-seminar Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Ronald Gansevoort

The coronavirus COVID-19 pandemic presented an unprecedented challenge to healthcare services worldwide in the previous months. The disease afflicts multiple organ systems and may also target kidney cells and cause acute kidney injury. On the other hand, patients with existing chronic kidney disease (CKD) are at a much higher risk for severe illness when infected. In response to the COVID-19 pandemic the European Renal Association- European Dialysis Transplantation Association (ERA-EDTA) established the European Renal Association COVID-19 Database (ERACODA) in March 2020 to investigate the clinical course, outcomes, and risk factors for mortality in kidney replacement patients with COVID-19. Related to this initiative and in an effort to spread the finest quality scientific knowledge and deliver the latest findings to the nephrology community, ERA-EDTA has organized a series of e-seminars on practical COVID-19 related aspects relevant to renal professionals. The third ERACODA seminar is dedicated to the practical COVID-related aspects of renal replacement therapy (RRT) with professors Luuk Hilbrands and Ron Gansevoort as moderators, professors Claudio Ronco and Rita Suri as presenters, and dr Casper Franssen and professor Mario Cozzolino as panelists.

Kidney replacement therapy in the ICU in patients with COVID-19: treatment considerations

Presenter: Prof. Claudio Ronco, Vicenza, Italy

Panellist: Dr. Casper Franssen, Groningen, the Netherlands

The first human cases of COVID-19 were reported in Wuhan city, China, in December 2019. The causative virus, SARS-CoV-2, and its genetic sequence were identified and shared publicly in mid-January 2020. Although the majority of patients presented without fever or significant symptoms, many still had a meaningful clinical picture and required hospitalization and intensive care (1).  At the time it was not possible to anticipate the extent of the epidemic and number of patients that would require intensive care, thus the promptly published recommendations on how to prepare for extracorporeal organ support in intensive care units (ICU) came very helpful (2, 3). It soon emerged that critically ill patients often needed multiple extracorporeal organ support (ECOS), including renal replacement therapy (RRT), thus necessitating a multidisciplinary approach to minimize negative interactions and unwanted adverse effects (4).

Acute kidney injury (AKI) was frequently observed in critically ill COVID-19 patients affected by different comorbidities. This may be ascribed to an enhanced inflammatory/immune reaction, local inflammatory response of infected kidney epithelial cells and the presence of pre-existing chronic decline of kidney function related to comorbidities (5). Other contributors to AKI may include volume depletion, immune response dysregulation, rhabdomyolysis, macrophage activation syndrome, hypercoagulability and endothelitis (6). In the absence of specific treatment options, extracorporeal blood purification techniques combined with anti-viral therapies were used to limit the systemic and local inflammatory response in such cases (6). Extracorporeal therapies effectively remove cytokines by direct hemoperfusion using a neutro-macroporous sorbent; plasma adsorption on a resin after plasma separation from whole blood; continuous RRT with hollow fiber filters with adsorptive properties; and high-dose continuous RRT with medium cut-off or high cut-off membranes (6, 7). Practical recommendations for RRT preparation, prescription, delivery and monitoring in critically ill COVID-19 patients were soon provided by a group of experts (Figure 1).

Figure 1. Management of COVID-related AKI with RRT (6)

Extracorporeal techniques can focus on virus removal, inflammatory mediators removal and/or organ support. Regrettably, virus removal with these procedures seems to be limited by low virus blood concentration. Inflammatory mediators, on the other hand, usually represent large middle molecules which can be successfully removed with the high cut-off membranes, but such intervention may be associated with unwanted albumin loss. The novel medium cut-off membranes, in turn, provide comparable efficiency in terms of cytokine removal, but with marginal albumin loss. Lowering cytokine storm can also be achieved by integrating sorbent membranes into RRT circuits or as a bypass in extracorporeal membrane oxygenation systems. These may improve mean arterial blood pressure, phagocytic capacity and monocyte tumor necrosis factor production and ability for antigen presentation. Thus, several exctracorporeal blood purification techniques can be applied in the treatment of critically ill COVID-19 patients with AKI, including hemoperfusion to remove inflammatory molecules and viral particles, therapeutic plasma exchange to remove inflammatory mediators and proteins associated with hypercoagulability, and continuous RRTs with adsorptive, medium cut-off or high cut-off membranes (8). A recently published set of practical recommendations for extracorporeal blood purification and organ support in the critically ill COVID-19 patients provide detailed review of the available technology and useful guidance for clinical practice (9). An early application of these strategies seem to mitigate the severity of the disease and prevent development of severe organ dysfunction.

 

 

How to prevent transmission of COVID-19 in the hemodialysis unit?

Presenter: Prof. Rita Suri, Quebec, Canada

Panellist: Prof. Mario Cozzolino, Milan, Italy

Hemodialysis (HD) patients appear to be at increased risk for COVID-19 infection and HD units are high-risk areas in this epidemic. Prevention of COVID-19 spread among maintenance HD patients involves identification of infected individuals, prevention of spreading within the HD unit, and reducing the risk outside the unit and at home. Patients should be advised and continuously encouraged to phone ahead the dialysis unit if they are sick, since individually phoning patients the day before their HD treatment has not proved to be effective. There should be a triage station at the dialysis unit entrance where nurses or other trained medical personnel should ask a standard set of questions about symptoms, history of exposure to a close contact with COVID-19 and, if applicable, travel history, and measure body temperature. Patient follow-up should continue vigorously during HD treatment. An example of the screening tool used at the McGill University Health Centre includes questions about the occurrence of fever, chills, cough, shortness of breath, loss of smell, new vomiting, and general unwellness, close contact with COVID-19 infected person in the last 14 days, as well as actual oxygen saturation and body temperature (Figure 2).

Figure 2. McGill University Health Center tablet screening tool for COVID-19 in HD patients

This screening strategy has been evaluated in a cross-sectional study involving four Canadian HD centers – three in the region highly affected by COVID-19 and one in the region with no registered COVID-19 cases. Out of 760 patients who were tested for COVID-19 76 turned out to be positive, and 35% of those were identified due to surveillance testing only. Only 40% of patients with COVID-19 had a fever ≥37.3°C, thus suggesting that body temperature may not be a reliable sole indicator of infection in this population. Nevertheless, even though screening with questionnaire or temperature ≥37.3°C had low sensitivity, it showed high specificity, with no major sex differences. Furthermore, sensitivity improved when the temperature threshold was set at 37°C. Thus, hyper-vigilance and screening with a questionnaire and temperature measurement at entrance to dialysis unit by trained medical personnel is of paramount importance. Systematic screening with nasopharyngeal swabs, on the other hand, is cumbersome and painful and should be reserved to high-risk patients and outbreak situations.

Based on the published reports, the Canadian Society of Nephrology issued a set of recommendations on the management of outpatient HD services to provide guidance for dialysis unit directors, clinicians and administrators on how to limit the infection (10). It is suggested that dialysis units should implement their own screening process to detect infected individuals, instruct patients to inform the dialysis unit about symptom development before their scheduled treatment, and educate them on how to safely isolate themselves from other residents in their household. All patients should wear a mask from the moment they leave their house until they return home and perform hand hygiene upon entry to and exit from the dialysis unit. Stable HD patients with COVID-19 may continue their treatment in an outpatient dialysis unit, but should be separated from other patients using droplet/contact precautions during dialysis treatment, transported in a private vehicle without other patients, escorted individually from the entrance of the building to dialysis unit, and assessed at each treatment (10, 11). Visits to patients should be completely restricted during the outbreaks. Local infection prevention and control team should be notified of patients with probable and confirmed COVID-19 to ensure contact tracing for all staff and patients. In case of shortage of isolation rooms, confirmed COVID-19 patients can be cohorted on a separate shift (10).

Nevertheless, ideal infection prevention and control measures may be difficult to implement in crowded HD units. Furthermore, type of facilities and their organization may differ substantially. Only 60% of HD units in Quebec have the capacity to distance dialysis stations >2 meters, 32% have the capacity to distance chairs in waiting rooms >2 meters, 70% have no negative-pressure isolation rooms, while 8% have no isolation rooms whatsoever. Still, even with these restrictions, 85% of units were able to successfully implement the recommended measures and no interpersonal transmission within the dialysis unit was reported during the first wave of infection in Quebec. Experiences from other HD centers may also be used as valuable tools to adapt local protocols (12).

References

1. Guan WJ, Ni ZY, Hu Y; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. DOI: 1056/NEJMoa2002032

2. Ronco C, Navalesi P, Vincent JL. Coronavirus epidemic: preparing for extracorporeal organ support in intensive care. Lancet Respir Med. 2020;8(3):240-241. DOI: 1016/S2213-2600(20)30060-6

3. Ronco C, Reis T, De Rosa S. Coronavirus epidemic and extracorporeal therapies in intensive care: si vis pacem para bellum. Blood Purif 2020;49(3):255-258. DOI: 1159/000507039

4. Ronco C, Ricci Z, Husain-Syed F. From Multiple Organ Support Therapy to Extracorporeal Organ Support in Critically Ill Patients. Blood Purif. 2019;48(2):99-105. DOI: 1159/000490694

5. Fanelli V, Fiorentino M, Cantaluppi V, Gesualdo L, Stallone G, Ronco C, Castellano G. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care. 2020;24(1):155. DOI: 1186/s13054-020-02872-z

6. Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med. 2020;8(7):738-742. DOI: 1016/S2213-2600(20)30229-0

7. Ronco C, Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol. 2020;16(6):308-310. DOI: 1038/s41581-020-0284-7

8. Nadim MK, Forni LG, Mehta RL, Connor MJ Jr, Liu KD, Ostermann M, Rimmelé T, Zarbock A, Bell S, Bihorac A, Cantaluppi V, Hoste E, Husain-Syed F, Germain MJ, Goldstein SL, Gupta S, Joannidis M, Kashani K, Koyner JL, Legrand M, Lumlertgul N, Mohan S, Pannu N, Peng Z, Perez-Fernandez XL, Pickkers P, Prowle J, Reis T, Srisawat N, Tolwani A, Vijayan A, Villa G, Yang L, Ronco C, Kellum JA. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol. 2020;16(12):747-764. DOI: 1038/s41581-020-00356-5

9. Ronco C, Bagshaw SM, Bellomo R, Clark WR, Husain-Syed F, Kellum JA, Ricci Z, Rimmelé T, Reis T, Ostermann M. Extracorporeal Blood Purification and Organ Support in the Critically Ill Patient during COVID-19 Pandemic: Expert Review and Recommendation. Blood Purif. 2021;50(1):17-27. DOI: 1159/000508125

10. Suri RS, Antonsen JE, Banks CA, Clark DA, Davison SN, Frenette CH, Kappel JE, MacRae JM, Mac-Way F, Mathew A, Moist LM, Qirjazi E, Tennankore KK, Vorster H. Management of Outpatient Hemodialysis During the COVID-19 Pandemic: Recommendations From the Canadian Society of Nephrology COVID-19 Rapid Response Team. Can J Kidney Health Dis. 2020;7:2054358120938564. DOI: 1177/2054358120938564

11. Rincón A, Moreso F, López-Herradón A, Fernández-Robres MA, Cidraque I, Nin J, Méndez O, López M, Pájaro C, Satorra À, Stuard S, Ramos R. The keys to control a COVID-19 outbreak in a haemodialysis unit. Clin Kidney J. 2020;13(4):542-549. DOI: 1093/ckj/sfaa119

12. Yau K, Muller MP, Lin M, Siddiqui N, Neskovic S, Shokar G, Fattouh R, Matukas LM, Beaubien-Souligny W, Thomas A, Weinstein JJ, Zaltzman J, Wald R. COVID-19 Outbreak in an Urban Hemodialysis Unit. Am J Kidney Dis. 2020;76(5):690-695. DOI: 1053/j.ajkd.2020.07.001

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