Autori: Giuseppe Stefano Netti (1,2), Fabio Sangregorio (2), Francesco Staffieri (3), Antonio Crovace (3), Barbara Infante (2), Annamaria Maiorano (2), Giulia Godeas (2), Giuseppe Castellano (4), Anna Maria Di Palma (4), Federica Spadaccino (1), Clelia Prattichizzo (1), Paola Pontrelli (4), Antonella Cotoia (5), Lucia Mirabella (5), Loreto Gesualdo (4), Gilda Cinnella (5), Elena Ranieri (1), Giovanni Stallone (2), Giuseppe Grandaliano (2).
Affiliazioni: (1) Clinical Pathology Unit and Center for Molecular Medicine, Dept. of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); (2) Nephrology Dialysis and Transplantation Unit, Dept. of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); (3) Veterinary Surgery Unit, Dept. of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari (Italy); (4) Nephrology Dialysis and Transplantation Unit, Dept. of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari (Italy); (5) Anesthesia and Intensive Care Unit, Dept. of Medical and Surgical Sciences, University of Foggia, Foggia (Italy).
Background
LPS-induced sepsisis 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.
Methods
Between Jan-2015 and Feb-2017, 43 consecutive patients with sepsis-induced AKI were treated with Coupled Plasma Filtration and Adsorption (CPFA) and/or direct hemoperfusion with Polymyxin B (DHP-PMX), because of a Gram- sepsis. Nine patients with AKI, in the absence of Gram- bacteriemia, treated with hemofiltration were employed as controls. 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. 3-hours after LPS infusion, animals were treated or not with CPFA for 6-hours.
Results
Patients with Gram- sepsis had higher basal proteinuria, serum C reactive protein (CRP), procalcitonin and pro-inflammatory cytokines compared to control group. Treatment with CPFA/DHP-PMX significantly reduced serum cytokines, CRP, procalcitonin and endotoxin levels. CPFA/DHP-PMX significantly lowered proteinuria and CD80 urinary excretion. CD80 glomerular expression, undetectable in control pigs, was markedly increasedat the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression.
Conclusions
Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the increased risk of CKD in sepsis-induced AKI.