Circulating cytokine levels predict the severity of renal failure in classic hemolytic uremic syndrome (HUS)

Introduction: Verotoxin-producing Escherichia coli (VTEC) cause hemorrhagic colitis (HC) Which may lead to HUS in 10% of cases. Experimental data suggests that the inflammatory response of the host is involved in the pathophysiology of VTEC infections. Methods: We measured the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 receptor antagonist (Ra)] mediators in serum samples obtained on admission, among 38 children with HUS due to Escherichia coli O157:H7 and among 12 normal controls. We compared the cytokine levels according to the severity of renal dysfunction. The latter was evaluated by the occurrence of oligoanuria, the requirement of dialysis, and a glomerular filtration rate (GFR) ≤80 mL/min/1.73 m² measured 1 year after enrolment. Results: Increased levels of IL-6, IL-10 and IL-1Ra were found in patients with HUS compared to controls (p<0.0001). Tenfold increased levels of IL-6 (p<0.0001) and 2.5 fold higher values of IL-1Ra (p<0.02) were found in children with oligoanuria (n=14) and those who required dialysis (n=14) than among those who maintained an adequate diuresis and who were not dialysed. Patients developping a decreased GFR at 1 year (n=8) also presented sixfold increased levels of IL-6 (p<0.001) and 2.5 fold higher values of IL-1Ra (p<0.07) than those recovering normal renal function. Conclusions: Our data show that the inflammatory response of the host is associated with the severity of renal dysfunction during the acute phase of classic HUS as well as 1 year after its occurrence.