Systemic inflammation in severe COVID-19 can cause acute kidney injury (AKI).
In a study of hospitalized patients with COVID-19, 46% developed AKI.4
Interestingly, the morphological and immunologic characteristics of COVID-19–associated AKI are similar to those of sepsis-associated AKI.5
When the body initiates inflammation to contain invasive pathogens and repair injury, the balance between pro- and anti-inflammatory cells and signals must be tightly calibrated to restore homeostasis and minimize collateral damage to tissues and organs.6
Uncontrolled inflammation, caused by imbalances in proinflammatory and anti-inflammatory signals, can be triggered by viral or bacterial infection, trauma, or surgery.7-9 COVID-19, like sepsis, can cause systemic inflammation.5,6
The kidneys and lungs are particularly sensitive to damage caused by systemic inflammation. Injury to these organs (eg, AKI or acute respiratory distress syndrome [ARDS], respectively) can initiate and perpetuate a vicious cycle of damaging systemic inflammation.10,11
Critical effector cells are the source of systemic inflammation.
Neutrophils and monocytes secrete a range of proinflammatory cytokines that initiate and propagate imbalanced immune responses.6 When dysregulated, neutrophils and monocytes can cause direct tissue damage.12
Elevation of specific cytokines and other inflammatory biomarkers predicts mortality in patients with COVID-19.13 These biomarkers decline as immune homeostasis is restored in patients who recover.13
Cytokine-directed approaches do not target critical effector cells; they target downstream mediators.14,15 Removing cytokines downstream without stopping the creation of additional cytokines does not produce consistent clinical outcomes.14,15
Many different cytokines are abnormally elevated during COVID-19–associated systemic inflammation, creating what is often referred to as a cytokine storm.6,13 Therapies targeting an individual cytokine pathway, such as interleukin-6, have not consistently reduced mortality in clinical trials of patients with COVID-19.15 Adsorption of cytokines via standard extracorporeal blood purification can remove both pro- and anti-inflammatory cytokines, which may fail to correct the imbalance between these types of mediators. Consequently, cytokine filters also have shown limited and inconsistent clinical benefit in patients with sepsis or COVID-19.15,16
The cytokines targeted by current therapies are continuously produced by critical effector cells that remain hyperactivated.14 Targeting effector cells to balance the immune response may initiate repair and recovery.12,14 Immunomodulation of neutrophils and monocytes may be a therapeutic strategy to stop systemic inflammation at the source.12,14
The selective cytopheretic device (SCD) is a cell-directed extracorporeal therapeutic approach to address systemic inflammation
The SCD
View the ASN poster, presented at Kidney Week 2021
ASN 2021 poster
SCD Treatment in COVID-19 ICU Patients With ARDS and AKI May Improve Clinical Outcomes
Interested in SCD clinical trials? Want to learn more? Contact us for more information.
References: 1. Cerdá J, Liu KD, Cruz DN, et al. Promoting kidney function recovery in patients with AKI requiring RRT. Clin J Am Soc Nephrol. 2015;10(10):1859-1867. https://doi.org/10.2215/CJN.01170215
2. Doyle JF, Forni LG. Acute kidney injury: short-term and long-term effects. Crit Care. 2016;20(1):188. https://doi.org/10.1186/s13054-016-1353-y
3. Tumlin JA, Galphin CM, Tolwani AJ, et al. A multi-center, randomized, controlled, pivotal study to assess the safety and efficacy of a selective cytopheretic device in patients with acute kidney injury. PLoS One. 2015;10(8):e0132482. https://doi.org/10.1371/journal.pone.0132482
4. Chan L, Chaudhary K, Saha A, et al. AKI in hospitalized patients with COVID-19. J Am Soc Nephrol. 2021;32(1):151-160. https://doi.org/10.1681/ASN.2020050615
5. Alexander MP, Mangalaparthi KK, Madugundu AK, et al. Acute kidney injury in severe COVID-19 has similarities to sepsis-associated kidney injury: a multi-omics study. Mayo Clinic Proceedings. 2021;96(10):2561-2575. https://doi.org/10.1016/j.mayocp.2021.07.001
6. Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383(23):2255-2273. https://doi.org/10.1056/NEJMra2026131
7. D’Elia RV, Harrison K, Oyston PC, Lukaszewski RA, Clark GC. Targeting the “cytokine storm” for therapeutic benefit. Clin Vaccine Immunol. 2013;20(3):319-327. https://doi.org/10.1128/CVI.00636-12
8. Singbartl K, Formeck CL, Kellum JA. Kidney-immune system crosstalk in AKI. Semin Nephrol. 2019;39(1):96-106. https://doi.org/10.1016/j.semnephrol.2018.10.007
9. Zhang WR, Garg AX, Coca SG, et al. Plasma IL-6 and IL-10 concentrations predict AKI and long-term mortality in adults after cardiac surgery. J Am Soc Nephrol. 2015;26(12):3123-3132. https://doi.org/10.1681/ASN.2014080764
10. Singbartl K, Bishop JV, Wen X, et al. Differential effects of kidney-lung cross-talk during acute kidney injury and bacterial pneumonia. Kidney Int. 2011;80(6):633-644. https://doi.org/10.1038/ki.2011.201
11. Park BD, Faubel S. Acute kidney injury and acute respiratory distress syndrome. Crit Care Clin. 2021;37(4):835-849. https://doi.org/10.1016/j.ccc.2021.05.007
12. Goldstein SL, Askenazi DJ, Basu RK, et al. Use of the selective cytopheretic device in critically ill children. Kidney Int Rep. 2021;6(3):775-784. https://doi.org/10.1016/j.ekir.2020.12.010
13. Abers MS, Delmonte OM, Ricotta EE, et al. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. 2021;6(1):144455. https://doi.org/10.1172/jci.insight.144455
14. Yessayan L, Szamosfalvi B, Napolitano L, et al. Treatment of cytokine storm in COVID-19 patients with immunomodulatory therapy. ASAIO J. 2020;66(10):1079-1083. https://doi.org/10.1097/MAT.0000000000001239
15. Rizvi MS, Gallo De Moraes A. New decade, old debate: blocking the cytokine pathways in infection-induced cytokine cascade. Crit Care Explor. 2021;3(3):e0364. https://doi.org/10.1097/CCE.0000000000000364
16. Ostermann M, Koyner JL. Extracorporeal blood purification is appropriate in critically ill patients with COVID-19 and multi-organ failure: commentary. Kidney360. Published online August 19, 2021:10.34067/KID.0005242021. https://doi.org/10.34067/KID.0005242021
17. Tumlin JA, Chawla L, Tolwani AJ, et al. The effect of the selective cytopheretic device on acute kidney injury outcomes in the intensive care unit: a multicenter pilot study. Semin Dial. 2013;26(5):616-623. https://doi.org/10.1111/sdi.12032
18. Yessayan LT, Neyra JA, Westover A, Szamosfalvi B, Humes HD. SCD treatment in COVID-19 ICU patients with ARDS and AKI may improve clinical outcomes. Poster presented at the: American Society of Nephrology Kidney Week; November 4-7, 2021; Virtual Meeting.
SeaStar Medical is a medical technology company that is focusing on redefining how extracorporeal therapies may reduce the consequences of excessive inflammation on vital organs. SeaStar Medical’s novel technologies rely on science and innovation to provide life-saving solutions to critically ill patients. It is developing and commercializing extracorporeal therapies that target the effector cells that drive systemic inflammation, causing direct tissue damage and secreting a range of pro-inflammatory cytokines that initiate and propagate imbalanced immune responses.
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