LPS removal reduces CD80-mediated albuminuria in critically ill patients with Gram-negative sepsis.
Am J Physiol Renal Physiol
; 316(4): F723-F731, 2019 04 01.
Article
de En
| MEDLINE
| ID: mdl-30672713
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lipopolysaccharides
/
Infections bactériennes à Gram positif
/
Maladie grave
/
Antigène CD80
/
Sepsie
/
Albuminurie
Type d'étude:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Am J Physiol Renal Physiol
Sujet du journal:
FISIOLOGIA
/
NEFROLOGIA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Italie