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Hemolytic Uremic Syndrome (HUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytope-nia, and acute renal failure. HUS is most commonly triggered by Shiga-like toxin (Stx)-producing bacteria (Stx-HUS). Non-Shiga toxin-associated HUS (non-Stx-HUS) affects a heterogeneous group of patients in whom an infection by Stx-producing bacteria can be excluded as cause of the disease. It can be sporadic or familial. Biochemical evidence suggested that alterations in the complement system play an important role in the pathological mechanisms of non-Stx-HUS. Subsequently, genetic studies have shown that the disease depends on the deficiency or abnormalities in complement regulatory proteins of the alternative pathway. About 30% of the patients have mutations in the gene encoding factor H (CFH); CFH is a protein that inhibits the activation of the alternative pathway of the complement system. More recent observations have also shown the involvement of genes that encode Membrane Cofactor Protein (MCP) and factor I (CFI). Genetic studies can be useful to improve therapeutic approach. Plasma infusion or plasma exchange are helpful treatments for patients with alterations in CFH or CFI, which are plasma proteins. On the other hand, plasma treatment in patients with alterations in MCP, a membrane-bound protein, does not impact the outcome significantly. Kidney transplantation outcome is favorable in patients with MCP mutations, whereas the outcome is poor in patients with CFH and CFI mutations due to disease recurrence. During the last years, genetic studies have allowed a better comprehension of pathological molecular mechanisms. The results will offer the rationale to develop new specific treatments for HUS.

Hemolytic uremic syndrome (HUS) is a disease characterized by non immune hemolytic anemia, low platelet count and renal impairment. In children, the disease is most commonly triggered by Shiga-like toxin (Stx)-producing Escherichia coli (Stx-E. Coli): however, renal function recovers in up to 70% of patients. Plasma infusion or exchange reduces mortality and the risk of end-stage renal disease (ESRD) in adult patients. Non-Shiga toxin-associated HUS (non-Stx-HUS), accounting for only 5-10% of all disease cases, can be sporadic or familial. Collectively, non-Stx-HUS forms have a poor outcome. Up to 50% of cases progress to ESRD or have irreversible brain damage, and 25% can die during the acute phase of the disease. Genetic studies have recently documented that the familial form is associated with genetic abnormalities of complement regulatory proteins, and evidence is now emerging that similar genetic alterations can predispose to sporadic cases of non-Stx-HUS as well. Mutations of genes encoding for factor H, a glycoprotein that plays an important role in the regulation of the alternative pathway of complement and for MCP, a widely expressed transmembrane glycoprotein with an inhibitory role of activated C3, are reported in familial HUS. These mutations are more likely to predispose rather than to cause the disease directly.

Infections in the digestive tract are due to multiple organism, which cause different syndromes. Escherichia coli O157:H7, already identified as a human pathogen in 1982, has been recognised as a major public health issue, being responsible for sporadic and epidemic cases of haemorrhagic colitis, often associated, in children and elderly, with the haemolytic uraemic syndrome. E. coli O157:H7 infection may occur everywhere, but is more frequent in North Europe, Canada, USA, Argentina and Japan, with annual incidence rates of 8 per 100,000 population. In Italy until 1997 the Italian National Institute of Health has identified 196 cases of haemolytic uraemic syndrome, in addition, an outbreak caused by E. coli O157:H7 occurred in 1993. In Italy the incidence of the haemolytic uraemic syndrome is 4-5 times lower than in Great Britain, Germany and other European countries. E. coli infection is more frequently associated with the ingestion of food from bovine and sheep origin and with infected water. The clinical spectrum includes an asymptomatic infection, non bloody diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome. When the E. coli infection is suspected, it is necessary to isolate the bacterium in a specialised laboratory. Treatment is essentially supportive in order to control anaemia and to maintain an adequate fluid and electrolyte balance, if necessary with the use of dialysis. The use of antimicrobial agents is currently under debate as there are controversial data on the risk of developing haemolytic uraemic syndrome.

Many pathogenetic factors may enhance coagulation process and induce thrombosis. The Authors report a case of hemolytic-uremic syndrome, with marked evidence of macroscopic kidney thrombotic involvement, in which an important dyslipidemia (hypertriglyceridemia and hypercholesterolemia) was detected during the phase of clinical improvement. These findings, and the contemporary marked reduction of fibrinolytic activity, seem to be relevant pathogenetic factors in this case. The treatment with polyunsaturated fatty acids Omega 3 may have been helpful in modifying these serum abnormalities and maybe could have brought to the clinical improvement.

Vero cytotoxin-producing strains of Escherichia coli (VTEC) appear to be in man associated with a range of clinical symptoms from mild non bloody diarrhoea to haemorrhagic colitis and severe haemolytic uraemic syndrome (HUS). We present two patients affected by HUS who were investigated to determine evidence of infection by VTEC. In one of the patient free fecal cytotoxin active on Vero cells was detected as well as seroconversion of VT-neutralizing antibody titre. Both children were living in the same county town, but all parents denied any animal contact. The source of infection was not identified but one child had eaten ground beef during the period immediately prior to the onset of symptoms. Epidemiological informations are presented and the results of a study on the possible animal reservoir are illustrated. Fecal cultures were performed on 38 stools specimen obtained from non diarrheal beef cattle and pork. One VT- producing Escherichia coli strain was isolated in pork faeces (20 stools sample) whereas two VTEC were found in cattle faeces (18 stool sample).