Autologous Cell Processing with the Selective Cytopheretic Device for the Treatment of Acute Kidney Injury Autologous Cell Processing with the SCD for the Treatment of AKI
Main Article Content
Abstract
Acute kidney injury continues to be a common and deadly condition despite medical advancements, occurring in upwards of half of all critically ill patients. Whether resulting from sepsis, the most common etiology, or from ischemic or nephrotoxic insults, acute kidney injury is associated with a systemic hyperinflammatory state that not only propagates additional kidney injury but often leads to injury of other organs as well. The Selective Cytopheretic Device is an autologous cell processing device that selectively targets and modifies the most inflammatory effector cells of the patients’ immune system to be in a less inflammatory state. As such, it is a novel approach to treating acute kidney injury by using cell-based rather than drug-based therapy with the aim of reducing inflammation, the causative factor of numerous disease states. Across multiple clinical trials, the selective cytopheretic device has demonstrated safety and efficacy as a treatment for acute kidney injury with reduced long term chronic dialysis sequelae, increased survival rates, and no device-related adverse events to date in both adult and pediatric populations. This innovative device has been granted FDA clearance under a Humanitarian Device Exemption to treat pediatric patients with sepsis associated acute kidney injury and its currently under evaluation in a pivotal trial in adults with renal injury as a step towards Pre-Market Approval. As the mechanism of action of the selective cytopheretic device lends it to be agnostic of the pathological cause, there is potential for it to be beneficial in treating other hyperinflammatory conditions as well.
Keywords:
Acute Kidney Injury (AKI), Selective Cytopheretic Device (SCD), Autologous Cell Therapy, Hyperinflammation, Sepsis-associated AKI, Renal Replacement Therapy, Pediatric Critical Care, Immunomodulation
Article Details
How to Cite
JONES, Sadie J et al.
Autologous Cell Processing with the Selective Cytopheretic Device for the Treatment of Acute Kidney Injury.
Medical Research Archives, [S.l.], v. 13, n. 8, aug. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6874>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i8.6874.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423.
2. Kister TS, Remmler J, Schmidt M, et al. Acute kidney injury and its progression in hospitalized patients-Results from a retrospective multicentre cohort study with a digital decision support system. PLoS One. 2021;16(7):e0254608.
3. Liano F, Junco E, Pascual J, Madero R, Verde E. The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney Int Suppl. 1998;66:S16-24.
4. McCarthy JT. Prognosis of patients with acute renal failure in the intensive-care unit: a tale of two eras. Mayo Clin Proc. 1996;71(2):117-126.
5. Metnitz PG, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002;30(9):2051-2058.
6. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818.
7. Makris K, Spanou L. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes. Clin Biochem Rev. 2016;37(2):85-98.
8. Yessayan L, Humes HD, Scribe EC, Iyer SPN, Chung KK. Rationale and Design of NEUTRALIZE-AKI: A Multicenter, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy. Nephron. 2024;148(1):43-53.
9. Deng J, Wu Z, He Y, Lin L, Tan W, Yang J. Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury. Front Med (Lausanne). 2022;9:954574.
10. Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2(3):431-439.
11. Mehta RL, Bouchard J, Soroko SB, et al. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease. Intensive Care Med. 2011;37(2):241-248.
12. Pais T, Jorge S, Lopes JA. Acute Kidney Injury in Sepsis. Int J Mol Sci. 2024;25(11).
13. Manrique-Caballero CL, Del Rio-Pertuz G, Gomez H. Sepsis-Associated Acute Kidney Injury. Crit Care Clin. 2021;37(2):279-301.
14. Kadatane SP, Satariano M, Massey M, Mongan K, Raina R. The Role of Inflammation in CKD. Cells. 2023;12(12).
15. Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol. 2012;2(2):1303-1353.
16. Rabb H, Griffin MD, McKay DB, et al. Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps. J Am Soc Nephrol. 2016;27(2):371-379.
17. Hanif M, Bali A, Ramphul K. Acute Renal Tubular Necrosis. Treasure Island (FL): StatPearls; 2023.
18. Akcay A, Nguyen Q, Edelstein CL. Mediators of inflammation in acute kidney injury. Mediators Inflamm. 2009;2009:137072.
19. Baker ML, Cantley LG. Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury. J Clin Invest. 2025;135(6).
20. Cantaluppi V, Quercia AD, Dellepiane S, Ferrario S, Camussi G, Biancone L. Interaction between systemic inflammation and renal tubular epithelial cells. Nephrol Dial Transplant. 2014;29 (11):2004-2011.
21. Armutcu F. Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions. Inflamm Res. 2019;68(10):825-839.
22. Doyle JF, Forni LG. Acute kidney injury: short-term and long-term effects. Crit Care. 2016;20(1):188.
23. Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255-2273.
24. Himmelfarb J, McMonagle E, Freedman S, et al. Oxidative stress is increased in critically ill patients with acute renal failure. J Am Soc Nephrol. 2004;15(9):2449-2456.
25. Mutunga M, Fulton B, Bullock R, et al. Circulating endothelial cells in patients with septic shock. Am J Respir Crit Care Med. 2001;163(1):195-200.
26. Simmons EM, Himmelfarb J, Sezer MT, et al. Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int. 2004;65(4):1357-1365.
27. Pino CJ, Yevzlin AS, Lee K, et al. Cell-based approaches for the treatment of systemic inflammation. Nephrol Dial Transplant. 2013;28(2):296-302.
28. Humes HD, Sobota JT, Ding F, Song JH, Group RADI. A selective cytopheretic inhibitory device to treat the immunological dysregulation of acute and chronic renal failure. Blood Purif. 2010; 29(2):183-190.
29. Pino CJ, Westover AJ, Johnston KA, Buffington DA, Humes HD. Regenerative Medicine and Immunomodulatory Therapy: Insights From the Kidney, Heart, Brain, and Lung. Kidney Int Rep. 2018;3(4):771-783.
30. Yessayan L, Sohaney R, Puri V, et al. Regional citrate anticoagulation "non-shock" protocol with pre-calculated flow settings for patients with at least 6 L/hour liver citrate clearance. BMC Nephrol. 2021;22(1):244.
31. Brophy PD, Somers MJ, Baum MA, et al. Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). Nephrol Dial Transplant. 2005;20(7):1416-1421.
32. Finn A, Rebuck N. Measurement of adhesion molecule expression on neutrophils and fixation. J Immunol Methods. 1994;171(2):267-270.
33. Hamblin A, Taylor M, Bernhagen J, et al. A method of preparing blood leucocytes for flow cytometry which prevents upregulation of leucocyte integrins. J Immunol Methods. 1992;146(2):219-228.
34. Westover AJ, Humes HD, Pino CJ. Immunomodulatory effects of a cell processing device to ameliorate dysregulated hyperinflammatory disease states. Sci Rep. 2024;14(1):12747.
35. Yessayan L, Pino CJ, Humes HD. Extracorporeal therapies in sepsis: a comprehensive review of the Selective Cytopheretic Device, Polymyxin B and Seraph cartridges. Ren Fail. 2025;47(1):2459349.
36. Humes HD, Goldstein SL, Yessayan LT, et al. Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure. Crit Care Explor. 2023;5(10):e0995.
37. Ding F, Yevzlin AS, Xu ZY, et al. The effects of a novel therapeutic device on acute kidney injury outcomes in the intensive care unit: a pilot study. ASAIO J. 2011;57(5):426-432.
38. Yessayan LT, Neyra JA, Westover AJ, Szamosfalvi B, Humes HD. Extracorporeal Immunomodulation Treatment and Clinical Outcomes in ICU COVID-19 Patients. Crit Care Explor. 2022;4(5):e0694.
39. Goldstein SL, Humes HD. Current Experience Using the Selective Cytopheretic Device for Continuous Immunomodulation in Acute Kidney Injury and Multiorgan Failure. Blood Purif. 2025.
40. Humes HD, Aaronson KD, Buffington DA, et al. Translation of immunomodulatory therapy to treat chronic heart failure: Preclinical studies to first in human. PLoS One. 2023;18(4):e0273138.
41. 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.
42. Yessayan LT, Sharma P, Westover AJ, Szamosfalvi B, Humes HD. Extracorporeal Immunomodulation Therapy in Acute Chronic Liver Failure With Multiorgan Failure: First in Human Use. ASAIO J. 2024;70(3):e53-e56.
43. Ribon M, Mussard J, Semerano L, Singer BB, Decker P. Extracellular Chromatin Triggers Release of Soluble CEACAM8 Upon Activation of Neutrophils. Front Immunol. 2019;10:1346.
44. Zhao L, Furebring M, Xu S, Venge P. Subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 in human neutrophils. Br J Haematol. 2004;125(5):666-673.
45. Silvestre-Roig C, Hidalgo A, Soehnlein O. Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood. 2016;127(18):2173-2181.
46. Moulding DA, Hart CA, Edwards SW. Regulation of neutrophil FcgammaRIIIb (CD16) surface expression following delayed apoptosis in response to GM-CSF and sodium butyrate. J Leukoc Biol. 1999;65(6):875-882.
47. Martin C, Burdon PC, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity. 2003;19(4):583-593.
48. Ayub K, Hallett MB. Ca2+ influx shutdown during neutrophil apoptosis: importance and possible mechanism. Immunology. 2004;111(1):8-12.
49. Whyte MK, Hardwick SJ, Meagher LC, Savill JS, Haslett C. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro. J Clin Invest. 1993;92(1):446-455.
50. Iyer SPN, Ollberding NJ, Koyner JL, Yessayan LT, Chung KK, Humes HD. The Impact of the Selective Cytopheretic Device on Neutrophil-to-Lymphocyte Ratios and Hematological Parameters in Acute Kidney Injury: A Pooled Analysis. Nephron. 2025:1-13.
51. DiStasi MR, Ley K. Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. Trends Immunol. 2009;30(11):547-556.
52. Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet. 2006;368(9530):157-169.
53. Kapellos TS, Bonaguro L, Gemund I, et al. Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases. Front Immunol. 2019;10:2035.
54. Ozanska A, Szymczak D, Rybka J. Pattern of human monocyte subpopulations in health and disease. Scand J Immunol. 2020;92(1):e12883.
55. Meng X, Jin J, Lan HY. Driving role of macrophages in transition from acute kidney injury to chronic kidney disease. Chin Med J (Engl). 2022;135(7):757-766.
56. Han HI, Skvarca LB, Espiritu EB, Davidson AJ, Hukriede NA. The role of macrophages during acute kidney injury: destruction and repair. Pediatr Nephrol. 2019;34(4):561-569.
57. Szamosfalvi B, Westover A, Buffington D, Yevzlin A, Humes HD. Immunomodulatory Device Promotes a Shift of Circulating Monocytes to a Less Inflammatory Phenotype in Chronic Hemodialysis Patients. ASAIO J. 2016;62(5):623-630.
58. 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.
59. Goldstein SL, Ollberding NJ, Askenazi DJ, et al. Selective Cytopheretic Device Use in Continuous Kidney Replacement Therapy in Children: A Cohort Study With a Historical Comparator. Kidney Medicine. 2024;6(4).
60. Di Marco GS, Chasan AI, Boeckel GR, et al. Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation. Int J Mol Sci. 2024;25(5).
61. 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.
62. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators A. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med. 2017;376(1):11-20.
63. Menon S, Starr MC, Zang H, et al. Characteristics and outcomes of children
64. Stanski NL, Gist KM, Hasson D, et al. Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). Crit Care Med. 2024;52(11):1686-1699.
65. 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.
66. Goldstein SL, Somers MJ, Baum MA, et al. Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int. 2005;67(2):653-658.
67. Shimizu T, Miyake T, Tani M. History and current status of polymyxin B-immobilized fiber column for treatment of severe sepsis and septic shock. Ann Gastroenterol Surg. 2017;1(2):105-113.
68. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003; 348(2):138-150.
69. Fujimori K, Tarasawa K, Fushimi K. Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan. Blood Purif. 2021;50(4-5):560-565.
70. Klein DJ, Foster D, Walker PM, Bagshaw SM, Mekonnen H, Antonelli M. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intensive Care Med. 2018;44(12):2205-2212.
71. Moreno RP, Metnitz B, Adler L, et al. Sepsis mortality prediction based on predisposition, infection and response. Intensive Care Med. 2008; 34(3):496-504.
72. Seffer MT, Cottam D, Forni LG, Kielstein JT. Heparin 2.0: A New Approach to the Infection Crisis. Blood Purif. 2021;50(1):28-34.
73. Mattsby-Baltzer I, Bergstrom T, McCrea K, Ward R, Adolfsson L, Larm O. Affinity apheresis for treatment of bacteremia caused by Staphylococcus aureus and/or methicillin-resistant S. aureus (MRSA). J Microbiol Biotechnol. 2011;21(6):659-664.
74. Chitty SA, Mobbs S, Rifkin BS, et al. A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19. Crit Care Explor. 2022;4(4):e0662.
75. Hambrick HR, Short K, Askenazi D, et al. Hemolytic Uremic Syndrome-Induced Acute Kidney Injury Treated via Immunomodulation with the Selective Cytopheretic Device. Blood Purif. 2023;52(9-10):812-820.
76. Goldstein SL, Yessayan LT, Krallman KA, et al. Use of extracorporeal immunomodulation in a toddler with hemophagocytic lymphohistiocytosis and multisystem organ failure. Pediatr Nephrol. 2023;38(3):927-931.
77. Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. 2025; 8(1):e2457349.
78. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18(3):363-374.
79. Jiang W, Li X, Xiang C, Zhou W. Neutrophils in pancreatic cancer: Potential therapeutic targets. Front Oncol. 2022;12:1025805.
80. Pratt HG, Steinberger KJ, Mihalik NE, et al. Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer. Cancers (Basel). 2021;14(1).
81. Raskov H, Orhan A, Christensen JP, Gogenur I. Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124(2):359-367.
82. Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66(4):1613-1621.
83. Waikar SS, Curhan GC, Wald R, McCarthy EP, Chertow GM. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006;17(4):1143-1150.
2. Kister TS, Remmler J, Schmidt M, et al. Acute kidney injury and its progression in hospitalized patients-Results from a retrospective multicentre cohort study with a digital decision support system. PLoS One. 2021;16(7):e0254608.
3. Liano F, Junco E, Pascual J, Madero R, Verde E. The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney Int Suppl. 1998;66:S16-24.
4. McCarthy JT. Prognosis of patients with acute renal failure in the intensive-care unit: a tale of two eras. Mayo Clin Proc. 1996;71(2):117-126.
5. Metnitz PG, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002;30(9):2051-2058.
6. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818.
7. Makris K, Spanou L. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes. Clin Biochem Rev. 2016;37(2):85-98.
8. Yessayan L, Humes HD, Scribe EC, Iyer SPN, Chung KK. Rationale and Design of NEUTRALIZE-AKI: A Multicenter, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy. Nephron. 2024;148(1):43-53.
9. Deng J, Wu Z, He Y, Lin L, Tan W, Yang J. Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury. Front Med (Lausanne). 2022;9:954574.
10. Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2(3):431-439.
11. Mehta RL, Bouchard J, Soroko SB, et al. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease. Intensive Care Med. 2011;37(2):241-248.
12. Pais T, Jorge S, Lopes JA. Acute Kidney Injury in Sepsis. Int J Mol Sci. 2024;25(11).
13. Manrique-Caballero CL, Del Rio-Pertuz G, Gomez H. Sepsis-Associated Acute Kidney Injury. Crit Care Clin. 2021;37(2):279-301.
14. Kadatane SP, Satariano M, Massey M, Mongan K, Raina R. The Role of Inflammation in CKD. Cells. 2023;12(12).
15. Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol. 2012;2(2):1303-1353.
16. Rabb H, Griffin MD, McKay DB, et al. Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps. J Am Soc Nephrol. 2016;27(2):371-379.
17. Hanif M, Bali A, Ramphul K. Acute Renal Tubular Necrosis. Treasure Island (FL): StatPearls; 2023.
18. Akcay A, Nguyen Q, Edelstein CL. Mediators of inflammation in acute kidney injury. Mediators Inflamm. 2009;2009:137072.
19. Baker ML, Cantley LG. Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury. J Clin Invest. 2025;135(6).
20. Cantaluppi V, Quercia AD, Dellepiane S, Ferrario S, Camussi G, Biancone L. Interaction between systemic inflammation and renal tubular epithelial cells. Nephrol Dial Transplant. 2014;29 (11):2004-2011.
21. Armutcu F. Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions. Inflamm Res. 2019;68(10):825-839.
22. Doyle JF, Forni LG. Acute kidney injury: short-term and long-term effects. Crit Care. 2016;20(1):188.
23. Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255-2273.
24. Himmelfarb J, McMonagle E, Freedman S, et al. Oxidative stress is increased in critically ill patients with acute renal failure. J Am Soc Nephrol. 2004;15(9):2449-2456.
25. Mutunga M, Fulton B, Bullock R, et al. Circulating endothelial cells in patients with septic shock. Am J Respir Crit Care Med. 2001;163(1):195-200.
26. Simmons EM, Himmelfarb J, Sezer MT, et al. Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int. 2004;65(4):1357-1365.
27. Pino CJ, Yevzlin AS, Lee K, et al. Cell-based approaches for the treatment of systemic inflammation. Nephrol Dial Transplant. 2013;28(2):296-302.
28. Humes HD, Sobota JT, Ding F, Song JH, Group RADI. A selective cytopheretic inhibitory device to treat the immunological dysregulation of acute and chronic renal failure. Blood Purif. 2010; 29(2):183-190.
29. Pino CJ, Westover AJ, Johnston KA, Buffington DA, Humes HD. Regenerative Medicine and Immunomodulatory Therapy: Insights From the Kidney, Heart, Brain, and Lung. Kidney Int Rep. 2018;3(4):771-783.
30. Yessayan L, Sohaney R, Puri V, et al. Regional citrate anticoagulation "non-shock" protocol with pre-calculated flow settings for patients with at least 6 L/hour liver citrate clearance. BMC Nephrol. 2021;22(1):244.
31. Brophy PD, Somers MJ, Baum MA, et al. Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). Nephrol Dial Transplant. 2005;20(7):1416-1421.
32. Finn A, Rebuck N. Measurement of adhesion molecule expression on neutrophils and fixation. J Immunol Methods. 1994;171(2):267-270.
33. Hamblin A, Taylor M, Bernhagen J, et al. A method of preparing blood leucocytes for flow cytometry which prevents upregulation of leucocyte integrins. J Immunol Methods. 1992;146(2):219-228.
34. Westover AJ, Humes HD, Pino CJ. Immunomodulatory effects of a cell processing device to ameliorate dysregulated hyperinflammatory disease states. Sci Rep. 2024;14(1):12747.
35. Yessayan L, Pino CJ, Humes HD. Extracorporeal therapies in sepsis: a comprehensive review of the Selective Cytopheretic Device, Polymyxin B and Seraph cartridges. Ren Fail. 2025;47(1):2459349.
36. Humes HD, Goldstein SL, Yessayan LT, et al. Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure. Crit Care Explor. 2023;5(10):e0995.
37. Ding F, Yevzlin AS, Xu ZY, et al. The effects of a novel therapeutic device on acute kidney injury outcomes in the intensive care unit: a pilot study. ASAIO J. 2011;57(5):426-432.
38. Yessayan LT, Neyra JA, Westover AJ, Szamosfalvi B, Humes HD. Extracorporeal Immunomodulation Treatment and Clinical Outcomes in ICU COVID-19 Patients. Crit Care Explor. 2022;4(5):e0694.
39. Goldstein SL, Humes HD. Current Experience Using the Selective Cytopheretic Device for Continuous Immunomodulation in Acute Kidney Injury and Multiorgan Failure. Blood Purif. 2025.
40. Humes HD, Aaronson KD, Buffington DA, et al. Translation of immunomodulatory therapy to treat chronic heart failure: Preclinical studies to first in human. PLoS One. 2023;18(4):e0273138.
41. 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.
42. Yessayan LT, Sharma P, Westover AJ, Szamosfalvi B, Humes HD. Extracorporeal Immunomodulation Therapy in Acute Chronic Liver Failure With Multiorgan Failure: First in Human Use. ASAIO J. 2024;70(3):e53-e56.
43. Ribon M, Mussard J, Semerano L, Singer BB, Decker P. Extracellular Chromatin Triggers Release of Soluble CEACAM8 Upon Activation of Neutrophils. Front Immunol. 2019;10:1346.
44. Zhao L, Furebring M, Xu S, Venge P. Subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 in human neutrophils. Br J Haematol. 2004;125(5):666-673.
45. Silvestre-Roig C, Hidalgo A, Soehnlein O. Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood. 2016;127(18):2173-2181.
46. Moulding DA, Hart CA, Edwards SW. Regulation of neutrophil FcgammaRIIIb (CD16) surface expression following delayed apoptosis in response to GM-CSF and sodium butyrate. J Leukoc Biol. 1999;65(6):875-882.
47. Martin C, Burdon PC, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity. 2003;19(4):583-593.
48. Ayub K, Hallett MB. Ca2+ influx shutdown during neutrophil apoptosis: importance and possible mechanism. Immunology. 2004;111(1):8-12.
49. Whyte MK, Hardwick SJ, Meagher LC, Savill JS, Haslett C. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro. J Clin Invest. 1993;92(1):446-455.
50. Iyer SPN, Ollberding NJ, Koyner JL, Yessayan LT, Chung KK, Humes HD. The Impact of the Selective Cytopheretic Device on Neutrophil-to-Lymphocyte Ratios and Hematological Parameters in Acute Kidney Injury: A Pooled Analysis. Nephron. 2025:1-13.
51. DiStasi MR, Ley K. Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. Trends Immunol. 2009;30(11):547-556.
52. Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet. 2006;368(9530):157-169.
53. Kapellos TS, Bonaguro L, Gemund I, et al. Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases. Front Immunol. 2019;10:2035.
54. Ozanska A, Szymczak D, Rybka J. Pattern of human monocyte subpopulations in health and disease. Scand J Immunol. 2020;92(1):e12883.
55. Meng X, Jin J, Lan HY. Driving role of macrophages in transition from acute kidney injury to chronic kidney disease. Chin Med J (Engl). 2022;135(7):757-766.
56. Han HI, Skvarca LB, Espiritu EB, Davidson AJ, Hukriede NA. The role of macrophages during acute kidney injury: destruction and repair. Pediatr Nephrol. 2019;34(4):561-569.
57. Szamosfalvi B, Westover A, Buffington D, Yevzlin A, Humes HD. Immunomodulatory Device Promotes a Shift of Circulating Monocytes to a Less Inflammatory Phenotype in Chronic Hemodialysis Patients. ASAIO J. 2016;62(5):623-630.
58. 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.
59. Goldstein SL, Ollberding NJ, Askenazi DJ, et al. Selective Cytopheretic Device Use in Continuous Kidney Replacement Therapy in Children: A Cohort Study With a Historical Comparator. Kidney Medicine. 2024;6(4).
60. Di Marco GS, Chasan AI, Boeckel GR, et al. Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation. Int J Mol Sci. 2024;25(5).
61. 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.
62. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators A. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med. 2017;376(1):11-20.
63. Menon S, Starr MC, Zang H, et al. Characteristics and outcomes of children
64. Stanski NL, Gist KM, Hasson D, et al. Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). Crit Care Med. 2024;52(11):1686-1699.
65. 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.
66. Goldstein SL, Somers MJ, Baum MA, et al. Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int. 2005;67(2):653-658.
67. Shimizu T, Miyake T, Tani M. History and current status of polymyxin B-immobilized fiber column for treatment of severe sepsis and septic shock. Ann Gastroenterol Surg. 2017;1(2):105-113.
68. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003; 348(2):138-150.
69. Fujimori K, Tarasawa K, Fushimi K. Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan. Blood Purif. 2021;50(4-5):560-565.
70. Klein DJ, Foster D, Walker PM, Bagshaw SM, Mekonnen H, Antonelli M. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intensive Care Med. 2018;44(12):2205-2212.
71. Moreno RP, Metnitz B, Adler L, et al. Sepsis mortality prediction based on predisposition, infection and response. Intensive Care Med. 2008; 34(3):496-504.
72. Seffer MT, Cottam D, Forni LG, Kielstein JT. Heparin 2.0: A New Approach to the Infection Crisis. Blood Purif. 2021;50(1):28-34.
73. Mattsby-Baltzer I, Bergstrom T, McCrea K, Ward R, Adolfsson L, Larm O. Affinity apheresis for treatment of bacteremia caused by Staphylococcus aureus and/or methicillin-resistant S. aureus (MRSA). J Microbiol Biotechnol. 2011;21(6):659-664.
74. Chitty SA, Mobbs S, Rifkin BS, et al. A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19. Crit Care Explor. 2022;4(4):e0662.
75. Hambrick HR, Short K, Askenazi D, et al. Hemolytic Uremic Syndrome-Induced Acute Kidney Injury Treated via Immunomodulation with the Selective Cytopheretic Device. Blood Purif. 2023;52(9-10):812-820.
76. Goldstein SL, Yessayan LT, Krallman KA, et al. Use of extracorporeal immunomodulation in a toddler with hemophagocytic lymphohistiocytosis and multisystem organ failure. Pediatr Nephrol. 2023;38(3):927-931.
77. Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. 2025; 8(1):e2457349.
78. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18(3):363-374.
79. Jiang W, Li X, Xiang C, Zhou W. Neutrophils in pancreatic cancer: Potential therapeutic targets. Front Oncol. 2022;12:1025805.
80. Pratt HG, Steinberger KJ, Mihalik NE, et al. Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer. Cancers (Basel). 2021;14(1).
81. Raskov H, Orhan A, Christensen JP, Gogenur I. Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124(2):359-367.
82. Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66(4):1613-1621.
83. Waikar SS, Curhan GC, Wald R, McCarthy EP, Chertow GM. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006;17(4):1143-1150.