ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: SA-PO138

Cholesterol Lipid Rafts When Blocked Prevent Epithelial-Mesenchymal Transition in Cisplatin-Induced Renal Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Gonzalez-Nicolas Gonzalez, Maria Angeles, Universidad Complutense, Madrid, Madrid, Spain
  • Humanes Sanchez, Blanca, Instituto de Investigación Sanitaria Gregorio Marañón (Hospital G.U. Gregorio Marañón), Madrid, Madrid, Spain
  • Camaño paez, Sonia, Instituto de Investigación Sanitaria Gregorio Marañón (Hospital G.U. Gregorio Marañón), Madrid, Madrid, Spain
  • Perez Fernandez, Veronica Astrid, Instituto de Investigación Sanitaria Gregorio Marañón (Hospital G.U. Gregorio Marañón), Madrid, Madrid, Spain
  • Tejedor jorge, Alberto, Universidad Complutense, Madrid, Madrid, Spain
  • Lazaro Fernandez, Alberto, Universidad Complutense, Madrid, Madrid, Spain

Cisplatin is a potent cytostatic, but its nephrotoxicity is a major complication and a dose limiting factor for anticancer therapy. Some evidences have shown that epithelial-mesenchymal transititon (EMT) contributes to the progression from acute renal failure to chronic renal failure. We have found that binding of cilastatin to renal dehydropeptidase-I inhibits transport and signalling of brush border lipid rafts in proximal tubule, thus providing protection.


In this study we investigated whether the protective effects of cilastatin are related to the prevention of the EMT-induced by cisplatin.
Male Wistar rats were divided into 4 groups: control rats, cilastatin-control rats, cisplatin-injected rats, cilastatin-treated cisplatin-injected rats. Nephrotoxicity was assessed 5 days after cisplatin treatment, by measuring serum creatinine, blood urea nitrogen (BUN), glomerular filtration ratio (GFR), proteinuria and renal morphology. Some typical markers of EMT and cell-cell adhesion were measured by western blot and immunohistochemical studies.


Cisplatin-treated rats showed significant elevations in BUN, creatinine, and proteinuria and decreased the GFR when compared with control rats. Cisplatin rats also exhibited severe morphological changes such as vacuolization and hyaline cast in the tubular lumen. Cilastatin significantly prevented partial or totally these changes in renal function and ameliorated histological damage in cisplatin-treated animals.
On the other hand, cisplatin increased transforming growth factor beta, connective tissue growth factor (inducers of EMT and profibrotic markers), and vimentin (mesenchymal cell marker) levels while decreased significantly β-catenin and zonula occludens-1 levels, both proteins involved in cell adhesion. Cilastatin treatment reversed these changes.


This study provides evidence that the protection offered by cilastatin to acute renal failure-induced by cisplatin, is associated to the prevention of the EMT by decreasing the signaling pathways that cause it and avoiding the loss of cell junctions. EMT signals seem to be triggered during the renal injudy-induced by cisplatin.


  • Government Support - Non-U.S.