Experiences with HUS in Canada: what have we learned about childhood HUS in Canada?

Experiences with childhood hemolytic uremic syndrome (HUS) in Canada will focus on the development of the Canadian Pediatric Kidney Disease Research Centre (CPKDRC) and the results of our collaborative research over a 13-year period (1985-1998).

Haemolytic uraemic syndrome is an immune-mediated disease: role of anti-CD36 antibodies.

Haemolytic uraemic syndrome (HUS) is a disorder in which platelet microthrombi are formed that have a particular propensity to deposit in the kidney microvasculature, resulting in impaired renal function and thrombocytopenia. The mechanism of formation of these microthrombi is not known. In this study, we showed that plasma from five adult and six paediatric cases of HUS caused aggregation and release of adenosine triphosphate from normal platelets. The plasma reacted against platelet lysate in a protein blot and all samples showed reactivity against a band at 88 kDa, corresponding to the membrane antigen CD36. This was confirmed by probing with Mo91, a monoclonal antibody to CD36. CD36 was also identified in the immune complex formed by incubation of patient plasmas with normal platelet lysate. In other studies, bands of 32 and 7.7 kDa were obtained when purified verotoxin was protein blotted and probed with either patient plasma or with anti-CD36 antibody Mo91 suggesting structural homologies between CD36 and verotoxin. While a direct cause-effect relationship is not yet established, the data support the concept of an immunological pathogenesis for HUS and suggest that molecular mimicry involving one or both of the homologous domains in membrane-bound CD36 and verotoxin lead to the development of antibodies capable of inducing the pathophysiological events characteristic of HUS.

Changing trends in the referral patterns of pediatric nephrology patients.

This study investigates the changing referral patterns of young patients to a tertiary pediatric nephrology center with a well-defined catchment area over two consecutive 8.5-year periods. We paid special attention to the known increase of obesity and diabetes mellitus in childhood. Demographic data (site of residence, height, weight, gender and renal diagnosis) were collected on 6,154 children aged 0-19 years, referred as in- and outpatients to the Children's Hospital of Eastern Ontario for nephrological work-up. Body mass index (BMI) Z-scores were calculated on the basis of data from the National (USA) Center for Health Statistics (2000). In 6,124 (99.5%) patients a final renal diagnosis could be made, allowing calculation of the incidence of a variety of renal diseases in pediatric patients, data that are not readily available. BMI increased significantly over the years, with a Z-score that rose from a median of +0.20 to +0.32 in the two 8.5-year study periods (p<0.0001). The increase in obesity coincided with a significant increase in the incidence of chronic renal insufficiency (CRI). The combined incidence of CRI and end stage renal disease rose from 0.994 to 2.334 per 100,000 children per year (p=0.0014). This study provides new information on the (changing) pattern of pediatric renal disease over almost two decades. Pediatric renal patients became progressively overweight and showed an increase in the incidence of CRI. This is the first time that this phenomenon, well known in adults, has been observed in the pediatric age group.

A randomized, placebo-controlled trial of prednisone in early Henoch Schönlein Purpura [ISRCTN85109383].

BACKGROUND: Henoch Schönlein Purpura (HSP) is the most common systemic vasculitis of childhood. There is considerable controversy over whether children with HSP should be treated with corticosteroids. The goal of this study was to investigate whether early corticosteroid administration could reduce the rate of renal or gastrointestinal complications in children with HSP. METHODS: Forty children with HSP, seen in the emergency room of a tertiary-care, paediatric centre, entered a randomized, double-blind, placebo controlled study. The treatment group (n = 21) received oral prednisone, 2 mg/kg/day for one week, with weaning over a second week, while the placebo group (n = 19) received an identical appearing placebo. Co-primary outcomes were the rate of renal involvement at one year and the rate of acute gastrointestinal complications. Co-primary outcomes were analysed using Fisher's Exact test. RESULTS: At one year, there was no difference in the rate of renal involvement (3/21 prednisone group vs. 2/19 placebo group, P = 1.0). There was also no statistically significant difference in the rate of acute gastrointestinal complications (2/21 prednisone group vs. 3/19 placebo group, P = 0.7). Two children in the placebo group did experience intussusceptions compared with none in the prednisone group (P = 0.2). CONCLUSIONS: Early prednisone therapy in HSP does not appear to reduce the risk of renal involvement at one year, or the risk of acute gastrointestinal complications. There may be a reduced risk of intussusception. The routine, early use of prednisone in uncomplicated HSP cannot be recommended at this time.

Hemolytic uremic syndrome: Events of the past decade.

This article describes the birth of the Canadian Pediatric Kidney Disease Research Centre (CPKDRC) in 1985 and the activities that have transpired as a result of collaborative research at paediatric centres across Canada. These include the National Retrospective Study of Childhood Hemolytic Uremic Syndrome (HUS), National Prospective Study of Risk Factors for Developing Escherichia coli O157:H7 Infection, and Intervention Studies for the Prevention of HUS. A look to the future describes possible studies to determine potential factors (surrogate markers) to identify children who are at risk for developing HUS following verotoxin-producing E coli gastroenteritis, other intervention studies and a more accurate understanding of permanent renal insufficiency in children who have had HUS.