Procalcitonin in Children with Escherichia coli O157:H7 Associated Hemolytic Uremic Syndrome

Abstract

Shiga toxin producing Escherichia coli (STEC) are noninvasive enteric pathogens that may cause hemorrhagic colitis (HC) and diarrhea-associated hemolytic uremic syndrome (Dϩ HUS). We hypothesized that development of Dϩ HUS is associated with increased serum procalcitonin (PCT) levels. PCT was measured by an immunoluminometric assay in 113 patients. Concentrations of PCT were different in normal controls, disease control groups (rotavirus enteritis, HC due to non-STEC pathogens, chronic renal failure), and children with uncomplicated O157:H7 HC or Dϩ HUS. Children with Dϩ HUS showed higher PCT levels than those with uncomplicated O157:H7 HC, and increased concentrations were noted in cases requiring peritoneal dialysis. Severely increased concentrations were observed in children with Dϩ HUS on d 5 or 6 after the onset of enteritis, whereas serial measurements in those with uncomplicated O157:H7 HC remained within the normal range throughout the first week of illness. PCT was correlated with serum concentrations of lipopolysaccharide (LPS)-binding protein and serum levels of alanine aminotransferase. Using two separate sets of real-time PCR primers, we were unable to detect elevated PCT mRNA transcripts in nonadherent undifferentiated (monocytic) or differentiated (macrophage-like) THP-1 cells stimulated with purified Shiga toxin-1 and/or LPS. Our data show that serum levels of PCT are associated with the severity of illness in children with Dϩ HUS. Further studies are needed to determine the role of PCT in the pathogenesis of thrombotic microangiopathy associated to childhood Dϩ HUS. (Pediatr Res 59: 579-583, 2006)

Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS)

“…In this regard, Shimizu et al identified five serum biomarkers, namely insulin growth factor-binding protein-2, angiopoietin-2, soluble IL-6 receptor, sTNFR type II (sTNFRII), and matrix metalloprotease protein-3, whose levels increase with HUS outcome and correlate with severity [95]. In addition, it has been reported that increased plasma concentrations of procalcitonin [101] are associated with severity of renal dysfunction during HUS.…”

Usefulness of serum procalcitonin as a diagnostic biomarker of infection in children with chronic kidney disease

“…Also, Lorton et al [27] concluded that increase of serum PCT in children with severe bacterial infections is mostly massive (10-fold to 1,000-fold), indicating a low risk for false negative results in these patients. Lastly, the study by Decaluwe et al [28] revealed that serum levels of PCT are associated with the severity of illness in children with diarrhea-associated hemolytic uremic syndrome.…”

Enterohemorrhagic Escherichia coli Pathogenesis and the Host Response

“…Proinflammatory and prothrombotic responses have been documented in HUS. Inflammatory and prothrombotic mediators, including cytokines, chemokines, soluble adhesion molecules, growth factors, cytokine receptors, tissue factor, and acute-phase response proteins, are elevated in patients with EHEC-associated infection and HUS (116,119,138,(157)(158)(159)(160)(161)(162)(163)(164)(165)(166)(167)(168)(169)(170)(171)(172)(173)(174) and could be correlated, in certain studies, to the progression of renal damage (reviewed in reference 89). Increased levels of chemoattractants, such as IL-8 (69), granulocyte colony-stimulating factor (159), and MCP-1 (157), could explain leukocyte influx.…”