Relative nephroprotection during Escherichia coli O157:H7 infections: Association with intravenous volume expansion

Julie A. Ake, Srdjan Jelacic, Marcia A. Ciol, Sandra L. Watkins, Karen F. Murray, Dennis L. Christie, Eileen J. Klein, Phillip I. Tarr*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

205 Scopus citations


Objective. The hemolytic uremic syndrome (HUS) consists of hemolytic anemia, thrombocytopenia, and renal failure. HUS is often precipitated by gastrointestinal infection with Shiga toxin-producing Escherichia coli and is characterized by a variety of prothrombotic host abnormalities. In much of the world, E coli O157:H7 is the major cause of HUS. HUS can be categorized as either oligoanuric (which probably signifies acute tubular necrosis) or nonoligoanuric. Children with oligoanuric renal failure during HUS generally require dialysis, have more complicated courses, and are probably at increased risk for chronic sequelae than are children who experience nonoligoanuric HUS. Oligoanuric HUS should be avoided, if possible. The presentation to medical care of a child with definite or possible E coli O157:H7 infections but before HUS ensues affords a potential opportunity to ameliorate the course of the subsequent renal failure. However, it is not known whether events that occur early in E coli O157:H7 infections, particularly measures to expand circulating volume, affect the likelihood of experiencing oligoanuric HUS if renal failure develops. We attempted to assess whether pre-HUS interventions and events, especially the volume and sodium content of intravenous fluids administered early in illness, affect the risk for developing oligoanuric HUS after E coli O157:H7 infections. Methods. We performed a prospective cohort study of 29 children with HUS that was confirmed microbiologically to be caused by E coli O157:H7. Infected children were enrolled when they presented with acute bloody diarrhea or as contacts of patients who were known to be infected with E coli O157:H7, or if they had culture-confirmed infection, or if they presented with HUS. HUS was defined as hemolytic anemia (hematocrit 30%, with fragmented erythrocytes on peripheral-blood smear), thrombocytopenia (platelet count of <150 000/mm3), and renal insufficiency (serum creatinine concentration that exceeded the upper limit of normal for age). A wide range of pre-HUS variables, including demographic factors, clinical history, medications given, initial laboratory values, and volume and content of parenteral fluid administered, were recorded and entered into analysis. Estimates of odds ratios were adjusted for possible confounding effects using logistic regression analysis. Twenty-nine children who were <10 years old, had HUS confirmed to be caused by E coli O157:H7, and were hospitalized at the Children's Hospital and Regional Medical Center, Seattle, were studied. The main outcome measured was development of oligoanuric renal failure. Oligoanuria was defined as a urine output <0.5 mL/kg per hour for at least 24 consecutive hours. Results. As a group, the children with oligoanuric renal failure presented to medical attention and were evaluated with laboratory testing later than the children with nonoligoanuric renal failure. On initial assessments, the children with oligoanuric outcomes had higher white blood cell counts, lower platelet counts and hematocrits, and higher creatinine concentrations than the children with nonoligoanuric outcomes, but these determinations probably reflect later points of these initial determinations, often when HUS was already developing. Stool cultures were obtained (medians of 3 vs 2 days, respectively) and positive (medians of 7 vs 4 days, respectively) at later points in illness in the children in the oligoanuric than in the nonoligoanuric group. Intravenous volume expansion began later in illness in the children who subsequently developed oligoanuric renal failure than in those whose renal failure was nonoligoanuric (medians: 4.5 vs 3.0 days, respectively). Moreover, the 13 patients with nonoligoanuric renal failure received more intravenous fluid and sodium before HUS developed (1.7- and 2.5-fold differences, respectively, between medians) than the 16 patients with oligoanuric renal failure. These differences were even greater when the first 4 days of illness were examined, with 17.1- and 21.8-fold differences, respectively, between medians. In a multivariate analysis adjusted for age, gender, antibiotic use, and free water volume administered intravenously to these children during the first 4 days of illness, the amount of sodium infused remained associated with protection against developing oligoanuric HUS. Dialysis was used in each of the children with oligoanuric renal failure and in none of the children with nonoligoanuric renal failure. The median length of stay in hospital after the diagnosis of HUS was 12 days in the oligoanuric group and 6 days in the nonoligoanuric group. Conclusions. Early recognition of and parenteral volume expansion during E coli O157:H7 infections, well before HUS develops, is associated with attenuated renal injury failure. Parenteral hydration in children who are possibly infected with E coli O157:H7, at the time of presentation with bloody diarrhea and in advance of culture results, is a practice that can accelerate the start of volume expansion during the important pre-HUS interval. Rapid assessment of stools for E coli O157:H7 by microbiologists and reporting of presumptive positives immediately can alert practitioners that patients are at risk for developing HUS and can prompt volume expansion in children who are not already being so treated. Our data also suggest that isotonic intravenous solutions might be superior to hypotonic fluids for use as maintenance fluids. Children who are infected with E coli O157:H7 and are given intravenous volume expansion need careful monitoring. This monitoring should be even more assiduous as HUS evolves.

Original languageEnglish
Pages (from-to)e673-e680
Issue number6
StatePublished - Jun 2005
Externally publishedYes


  • Acute tubular necrosis
  • Escherichia coli O157:H7
  • Hemolytic uremic syndrome
  • Isotonic crystalloid
  • Sodium


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