Abstract: TH-PO035
Cilastatin in the Prevention and Treatment of Lipopolysaccharide-Induced AKI
Session Information
- AKI: Epidemiology, Risk Factors, and Prevention - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Gonzalez-Nicolas Gonzalez, Maria Angeles, Universidad Complutense de Madrid Facultad de Medicina, Madrid, Comunidad de Madrid, Spain
- Lazaro Fernandez, Alberto, Universidad Complutense de Madrid Facultad de Medicina, Madrid, Comunidad de Madrid, Spain
Group or Team Name
- Renal Physiopathology Laboratory.
Background
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a significant cause of death in critically ill patients. In hospital mortality rate for patients with sepsis is about 15%–25%. Acute kidney injury (AKI) is the most complication of sepsis and is recognized as an independent factor for elevated lethality. More than 50% of patients with sepsis develop AKI, and sepsis associated AKI increases the risk of developing chronic comorbidities. Cilastatin, a renal dehydropeptidase-I inhibitor, has demonstrated its usefulness in the protection of AKI induced by nephrotoxic drugs. Here, we evaluate the utility of cilastatin as a protector against renal damage induced by lipopolysaccharide (LPS).
Methods
Sepsis was induced in Male Wistar rats by administering LPS 10 mg/kg bw i.p. (or its vehicle). Cilastatin 150 mg/kg bw i.p. (or its vehicle), was administered concomitantly and the animals were sacrificed at 24h. Kidney function was assessed by measuring serum creatinine, blood urea nitrogen (BUN), glomerular filtration rate (GFR), proteinuria, renal tissue morphology, kidney injury molecule 1 (KIM-1), as well as apoptotic, oxidative and inflammatory parameters.
Results
LPS-administrated rats showed significant elevations in BUN, creatinine and proteinuria, and decreased the GFR when compared with control rats. These renal effects of sepsis were confirmed by the increased in the KIM-1 and exhibited severe morphological changes such as vacuolization, swelling of tubular cells, brush border loss and hyaline cast in the tubular lumen. Also, apoptotic, inflammatory and oxidative biomarkers were increased. Cilastatin, prevented these changes in renal function in LPS treated animals, decreasing significantly all other parameters (as shown by reductions of BUN, creatinine and proteinuria and increased GFR), restoring KIM-1 levels to normal control and reducing many of the histological symptoms of renal damage.
Conclusion
Our findings support the potential use of cilastatin as a useful drug in the prevention and treatment of AKI-induced by LPS. Therefore, cilastatin could be a very beneficial therapeutic strategy for septic patients susceptible to renal damage in clinical practice.
Funding
- Government Support – Non-U.S.