Clinical relevance of shiga toxin concentrations in the blood of patients with hemolytic uremic syndrome

Background: Intestinal infections with Shiga toxin-producing Escherichia coli (STEC) in children can lead to the hemolytic uremic syndrome (HUS). Shiga toxins (Stx) released in the gut by bacteria enter the blood stream and target the kidney causing endothelial injury. Free toxins have never been detected in the blood of HUS patients, but they have been found on the surface of polymorphonuclear leukocytes (PMN). Methods: With respect to their clinical features, the clinical relevance of the amounts of serum Stx (cytotoxicity assay with human endothelial cells) and PMN-bound Stx (cytofluorimetric assay) in 46 patients with STEC-associated HUS was evaluated. Results: Stx-positive PMN were found in 60% of patients, whereas negligible amounts of free Stx were detected in the sera. Patients with high amounts of Stx on PMN showed preserved or slightly impaired renal function (incomplete form of HUS), whereas cases with low amounts of Stx usually presented evidence of acute renal failure. Conclusions: These observations suggest that the extent of renal damage in children with STEC-associated HUS could depend on the concentration of Stx present on their PMN and presumably delivered by them to the kidney. As previously shown by experimental models from our laboratory, high amounts of Stx could induce a reduced release of cytokines by the renal endothelium, with a consequent lower degree of inflammation. Conversely, low toxin amounts can trigger the cytokine cascade, provoking inflammation, thereby leading to tissue damage.