Development of an experimental hemolytic uremic syndrome in rats

Abstract

Escherichia coli strains producing Shiga toxins (Stxs) colonize the lower gastrointestinal tract and cause watery diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Oliguria associated with acute tubular necrosis and microangiopathic thrombosis has been reported as the most common cause of renal failure in Argentinean children. Our study was undertaken to obtain a model of HUS in rats that was similar to the clinical and renal histopathology findings described in humans. Rats were intraperitoneally inoculated with culture supernatant from recombinant E. coli expressing Stx2. Glomerular filtrate volume evaluated from clearance of creatinine resulted in a progressive reduction (from 53% at 24 h to 90% at 48 h). Urine volume increased significantly at 24 h but returned to normal levels at 48 h. Evidence of thrombocytopenia, anemia and leukocytosis was documented. Macroscopic analysis revealed a hyperemic peritoneal face with intestinal water accumulation. The kidneys were friable and congestive. Histopathological analysis showed glomerular and tubular necrosis as well as microangiopathic thrombosis. Our findings indicated vascular damage and kidney lesions similar to those described in humans with HUS.

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Acknowledgments

This paper was presented at the 50th Annual Scientific Meeting, Argentine Society of Clinical Investigation (SAIC), Mar del Plata, Argentina, 29th November to 2nd December, 2005, and the 6th International Symposium on Shiga toxin (Verocytotoxin-producing Escherichia coli infection, Melbourne, Australia, 29th October to 1st November, 2006. This work was supported by the University of Buenos Aires (M038, M827), the National Council of Research (CONICET, PIP 5587) and ANPCYT (PICT-26224). The authors gratefully acknowledge Claudio Mirabelli for his excellent technical assistance.

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Correspondence to Cristina Ibarra.

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Zotta, E., Lago, N., Ochoa, F. et al. Development of an experimental hemolytic uremic syndrome in rats. Pediatr Nephrol 23, 559–567 (2008). https://doi.org/10.1007/s00467-007-0727-4

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Keywords

  • Hemolytic uremic syndrome
  • Acute tubular necrosis
  • Thrombotic microangiopathy
  • Shiga toxin
  • Diarrhea