PRESENTED BY
CLAUDIO RONCO

Presentation Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Claudio Ronco

The novel coronavirus disease (COVID-19) is an acute, sometimes severe, non-specific respiratory syndrome accompanied by a generalized inflammatory response caused by a novel coronavirus SARS-CoV2. It was first reported in late 2019 in Wuhan, China, and has since spread in China and globally. Retrospective analysis has linked the first cases to a live animal market in Wuhan, suggesting initial zoonotic transmission. The virus was identified and its genetic sequence shared publicly in early January 2020. All available evidence to date suggests that the virus has an ecological origin in bat populations. The most common symptoms in patients with a severe form of the disease were fever and cough, while the typical patterns on chest CT were ground-glass opacity and bilateral patchy shadowing (1).

Since it was not possible to anticipate the extent of the epidemic and the number of affected patients who would require intensive care management, the personnel in intensive care units (ICU) had to be prepared and trained for early and optimal interventions, including the extracorporeal organ support therapies (2). In many cases, a single form of extracorporeal organ support (ECOS) may be required, but multiple organ support therapy was also mandatory in many cases (Figure 1). Most of these techniques are modifications of extracorporeal blood purification techniques, such as hemodialysis or hemofiltration (3). The idea for their application in septic patients originates from the occasional observation that treatment with renal replacement therapy (RRT) for acute kidney injury (AKI) displayed rapid and significant improvement in hemodynamics in sepsis (3). Thus, it has been hypothesized that timely initiation of blood purification techniques may decrease the proinflammatory and anti-inflammatory mediators, avoiding a “toxic threshold” to be reached, and improve the prognosis (4, 5). However, blood purification mechanisms of action are not yet completely understood and further research is needed to elucidate the process and determine the optimal initiation, timing and duration. The currently employed ECOS techniques are presented in Figure 1.

Figure 1. The current ECOS techniques (3, 6)
Legend: ECCO2R, extracorporeal CO2 removal; VA-ECMO, venous arterial extracorporeal membrane oxygenation; SCUF, slow continuous ultrafiltration; CVVH, continuous veno-venous hemofiltration; CVVHD, continuous veno-venous hemodialysis; CVVHDF, continuous veno-venous Hemodiafiltration; SLED, sustained low-efficiency hemodialysis; PF, plasmapheresis; PE, plasma exchange; HP, hemoperfusion; AHD, albumin hemodialysis; CPFA, continuous plasma filtration adsorption; VV-ECMO, veno- venous extracorporeal membrane oxygenation.

The pathophysiological mechanisms of AKI in COVID-19 patients
As many as 40% of patients with a severe form of COVID-19 may develop AKI, while around 20% may require RRT (7). Determining the risk of developing AKI in SARS-CoV-2 infected patients is an important step for the patient’s prognosis and early implementation of preventive and protective measures (7). Since the classical AKI indicators, serum creatinine and urine output, represent only established kidney damage, much attention has focused on novel biomarkers, particularly on markers of acute tubular stress and/or damage (7).

The origin of AKI in COVID-19 is complex and multifactorial and may occur as a result of intrarenal inflammation, increased vascular permeability, volume depletion and cardiomyopathy (8). Autopsy reports indicate that the virus can directly infect the renal endothelial cells, tubular epithelium and podocytes through an angiotensin-converting enzyme 2-dependent pathway, thus causing renal endothelial damage, collapsing glomerulopathy and acute tubular necrosis (8). Volume depletion at admission may be a common trigger for AKI since patients typically present with fever and pre-admission fluid replenishment is rarely performed (8). Cardio-renal syndrome, and particularly right ventricular failure secondary to pneumonia, might lead to kidney congestion and subsequent AKI. Left ventricular dysfunction, on the other hand, may cause arterial underfilling and kidney hypoperfusion (9). Other potential mechanisms of AKI include SARS-CoV-2-related immune response dysregulation, rhabdomyolysis, macrophage activation syndrome, and development of microemboli and microthrombi in the context of hypercoagulability (8).

Treatment options for AKI in COVID-19 patients
Conservative management of AKI in COVID-19 patients requires careful correction and constant monitoring of volume status to regulate commonly present volume depletion, but avoid volume overload and reduce the risk of pulmonary edema, right ventricular overload, congestion and subsequent AKI (9). Continuous RRT is the preferred modality of hemodialysis in hemodynamically unstable patients with COVID-19 who failed to respond to conservative measures (9). Detailed guidance on how to manage AKI with continuous RRT is presented in Figure 2 of reference 9 (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30229-0/fulltext#figures)

 

In the absence of established treatment options for COVID-19, the pathophysiological rationale might support the application of hemoperfusion with sorbent cartridges to prevent cytokine-induced kidney damage in specific cases (9). Remarkable benefits have been reported with the use of direct hemoperfusion cartridges containing highly biocompatible sorbents and microporous resins in terms of hemodynamic support and organ function recovery (9). Furthermore, the use of a microbind affinity filter which appears to capture and remove both the proinflammatory cytokines and the virus from the patients’ blood also presented promising results. Another option is the high retention onset medium cut-off membranes, which successfully modulate inflammation by removing the soluble mediators while ensuring the retention of albumin. The AN69-based oXiris membrane, modified with a positively charged poly-imine ethylene layer is also capable of adsorbing and effectively removing inflammatory mediators tumor necrosis factor α and interleukins 1, 6, 8 and 10 (6).

References

1. Guan WJ. Ni ZY, Liang WH, et al. Clinical characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020;382(18):1708-1720.

2. Ronco C, Navalesi P, Vincent JL. Coronavirus epidemic: preparing for extracorporeal organ support in intensive care. Lancet Respiratory Medicine 2020;8(3):240-241.

3. 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.

4. Ronco C, Tetta C, Mariano F, et al. Interpreting the Mechanisms of Continuous Renal Replacement Therapy in Sepsis: The Peak Concentration Hypothesis Artif Organs 2003;27:792-801.

5. Giardot T, Schneider A, Rimmele T. Blood Purification Techniques for Sepsis and Septic AKI. Semin Nephrol 2019; 39(5):505-514.

6. Ronco C. AKI in Covid-19 patients: mechanisms and management. Presented at the 57th ERA-EDTA Congress (fully virtual), June 6, 2020. Available on the Virtual Meeting

7. Fanelli V, Fiorentino M, Cantaluppi V, et al. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care 2020;24(1):155.

8. Ronco C, Reis T. Kidney Involvement in COVID-19 and Rationale for Extracorporeal Therapies. Nat Rev Nephrol 2020;16(6):308-310.

9. Ronco C, Reis T, Husain-Syed F. Management of Acute Kidney Injury in Patients With COVID-19. Lancet Respir Med 2020;S2213-2600.

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