LPS removal reduces CD80-mediated albuminuria in critically ill patients with gram-negative sepsis

Giuseppe Grandaliano, Giuseppe Stefano Netti, Fabio Sangregorio, Federica Spadaccino, Francesco Staffieri, Antonio Crovace, Barbara Infante, Annamaria Maiorano, Giulia Godeas, Giuseppe Castellano, Anna Maria Di Palma, Clelia Prattichizzo, Antonella Cotoia, Lucia Mirabella, Loreto Gesualdo, Gilda Cinnella, Giovanni Stallone, Elena Ranieri

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

6 Citazioni (Scopus)

Abstract

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomized to either have coupled plasma filtration and adsorption (CPFA) added to the standard care (n = 35) or not (n = 35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria, and CD80 expression in Gram sepsis, a swine model of LPS-induced AKI was set up. Three hours after LPS infusion, animals were treated or not with CPFA for 6 h. Treatment with CPFA significantly reduced serum cytokines, C-reactive protein, procalcitonin, and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.
Lingua originaleEnglish
pagine (da-a)F723-F731
Numero di pagine8
RivistaAMERICAN JOURNAL OF PHYSIOLOGY. RENAL, FLUID AND ELECTROLYTE PHYSIOLOGY
Volume316
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • APACHE
  • Acute kidney injury
  • Adsorption
  • Adult
  • Aged
  • Albuminuria
  • Animals
  • B7-1 Antigen
  • CD80
  • Chronic kidney disease
  • Critical Illness
  • Cytokines
  • Female
  • Filtration
  • Gram-Positive Bacterial Infections
  • Humans
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Sepsis
  • Swine

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