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Abstract: FR-PO096

Prevention of Renal Damage Caused by Activation of Rhabdomyolysis-Induced Inflammasome

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention


  • Gonzalez-Nicolas Gonzalez, Maria Angeles, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Comunidad de Madrid, Spain
  • Humanes Sanchez, Blanca, Instituto de Investigacion Sanitaria Gregorio Maranon, 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.

Rhabdomyolysis (RM) is a clinical and biochemical syndrome characterized by skeletal muscle rupture and massive release of cellular components including myoglobin (MG), which causes one of the most serious complications, acute renal failure (ARF) by direct cytotoxicity and tubular obstruction due to precipitation of MG itself. The heme group induces an inflammatory response by activation of the NLRP3 inflammasome, release of different cytokines and the phenotype changes of proinflammatory (M1) to antiinflammatory (M2) macrophages. Cilastatin, a renal dehydropeptidase-I inhibitor, has demonstrated its usefulness in the protection of ARF induced by nephrotoxic drugs due to interference with lipid rafts. We evaluate if cilastatin is able to block inflammasome activation and protect from RM-induced renal damage.


RM was induced in Wistar rats by administering in the hind legs with 50% glycerol (or vehicle to the control group). Cilastatin (150 mg/kg) or its vehicle, was administered immediately and every 24h after RM induction. Renal damage was assessed 48h after glycerol/vehicle administration by measuring serum levels of creatinine, potassium, LDH, blood urea nitrogen (BUN) and glomerular filtration rate (GFR), as well as morphology in renal tissue and ferric iron, specific biomarkers of inflammasome activation, also phenotype change in macrophages.


RM worsened renal function compared to the control group, which was confirmed by the presence of severe morphological changes and iron accumulation in tubular cells, as well as a statistically significant increase of the biomarkers of inflammasome and cytokines levels, along with a change in phenotype M1 to M2. Cilastatin treatment completely prevented renal dysfunction, restored significantly all other parameters to levels found in the control groups, and reduced many of the histological symptoms of renal damage.


Our results support the theory of a possible use of cilastatin in the prevention and treatment of ARF-induced by RM. Therefore, cilastatin may be a very beneficial therapeutic strategy in clinical practice for patients with some type of trauma or susceptible to renal damage due to RM.


  • Government Support – Non-U.S.