Development of an experimental hemolytic uremic syndrome in rats.
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.
Zotta
Elsa
E
Laboratorio de Fisiopatogenia, Depto de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Lago
Nestor
N
Ochoa
Federico
F
Repetto
Horacio A
HA
Ibarra
Cristina
C
D000208:Acute Disease; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003404:Creatinine / Q000652:urine; D003967:Diarrhea / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D022641:Shiga Toxin 2 / Q000378:metabolism / Q000633:toxicity*; D054323:Shiga-Toxigenic Escherichia coli / Q000502:physiology*; D014709:Vero Cells
D022641:Shiga Toxin 2; D003404:Creatinine