Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic disorders. Among the identified causes of HUS are infections, particularly infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement disorders, and disorders interfering with the degradation of von Willebrand factor (VWF). Other causes for atypical HUS include the cobalamin metabolism; pregnancy/hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP); drugs; and other disorders (e.g., systemic diseases appearing as HUS, such as systemic lupus erythematosus and rejection after transplantation). The group not related to STEC is often also called atypical HUS. Most of the occurrences of infectious HUS have only one episode. Recurrent episodes (recurrent HUS) have strong relationships to diseases of the complement system. In these two subgroups the prognosis is poor, with severe renal insufficiency, together with the need for renal replacement therapy. Severe arterial hypertension is common. Treatment options are limited. To better define this group of patients, the European Society for Pediatric Nephrology supported an initiative to develop a European HUS registry. In this registry, 167 patients were acquired; 73 were female (43.8%). The year of onset of the disease ranged from 1974 to 2005. The prevalence of atypical HUS/recurrent HUS can be calculated as 3.3 per million child population (< 18 years). Underlying disorders included factor H, factor I, MCP-1, pneumococci, and von Willebrand factor disturbances. In 33 patients at least one renal transplantation was performed (total, 55 kidneys); 18% were successful and 73% demonstrated recurrence or thrombosis. Treatment options were plasma substitution or plasmapheresis. Despite continued efforts, transplantation is not recommended at present for these patients. Living-related transplantation should be abandoned. New therapeutic strategies are urgently needed.

Based on this preliminary data, GCV(w) showed considerable variation but did not correlate with fasting times in children and adolescent patients. Recommended fasting times were often exceeded.

Recurrent hemolytic uremic syndrome (recHUS) is a heterogeneous group of disorders. The pathogenesis of recHUS is not fully understood. recHUS has a high risk of development of terminal renal insufficiency and other sequelae. Abnormalities in complement factor H or in membrane-bound complement inhibitors with consecutive complement activation can be found in approximately 30 to 50% of the patients. Starting in 2001, we evaluated 42 patients with recHUS from five European countries (Germany, Austria, Hungary, Switzerland, and the Czech Republic). We measured the terminal complement complex (TCC) by an enzyme-linked immunosorbent assay using a neoepitope-specific anti-C9 antibody in 17 patients in plasma (native complement activation), serum (after coagulation), and zymosan-activated serum (Z-serum; after stimulation of coagulation). We compared the results to those of 16 healthy persons. In patients with recHUS (eight males, nine females) with a median age of 10.8 years, the TCC values were higher in plasma (0.57 versus 0.48 microg/mL; P = 0.04) and serum (3.1 versus 2.2 microg/mL) than in those of the control group, with a median age of 28.6 years (six males, 10 females) The TCC values in patients with low C3 compared with patients with normal C3 levels were even higher in plasma and serum, and the ratio was much lower. Children with recHUS have higher concentrations of TCC in plasma and serum. The ratio of Z-serum to serum showed significantly lower values in children with recHUS (96.01 versus 150.3; P = 0.01). These findings indicate a higher grade of complement activation and consumption in recHUS, suggesting that TCC may mediate cell toxicity. This may play an important role in the inferior outcome of these patients. The isolated substitution of factor H, or other complement inhibitors to block TCC formation, may represent useful therapies for these patients.

Haemolytic uraemic syndrome (HUS) is the primary diagnosis of 4.5% of children on chronic renal replacement therapy. Approximately 5% of all HUS cases have an "atypical" or recurrent course. Atypical HUS is an inadequate term that applies to a heterogeneous group of conditions. We describe this group as non-diarrhoeal (D-) ), non-EHEC (EHEC - ) HUS. Patients in the non-diarrhoeal, non-EHEC, relapsing group are much more likely to exhibit severe hypertension, histological findings of arterial as well as arteriolar disease, chronic and end-stage renal failure. In general, these patients have an alarmingly high risk of graft loss from disease recurrence or thrombosis ranging from 60-100%. Family history is crucial, and where family members have relapsing disease, transplantation is a very high risk procedure (recurrence 100%). Patients with (D-)HUS need very careful consideration before transplantation, including molecular investigation of complement regulators (and von Willebrandt protease (ADAMTS13) activity, although this goes beyond the scope of this review). Guidelines are accessible under http://www.espn.ucwm.ac.uk . On no account should live related donation take place unless the risks of graft loss are understood. International collaboration to identify safer ways of transplanting these challenging patients is urgently needed.

Cytomegalovirus (CMV) is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV) transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactivation of latent virus or re-infection with a new strain of CMV) contribute to a much greater proportion of symptomatic cCMV than was previously thought. Here, we describe a case of symptomatic cCMV infection in the newborn of a woman with proven immunity prior to pregnancy. Diagnosis was confirmed by CMV PCR from amniotic fluid and fetal MR imaging. The newborn presented with typical cCMV symptoms including jaundice, hepatosplenomegaly, cholestasis, petechiae, small head circumference, and sensorineural hearing loss, the most common neurologic sequela. CMV was detected in infant blood and urine by PCR, and intravenous ganciclovir was initiated and continued orally for 6 weeks totally. Apart from persisting right-sided deafness, the child exhibited normal neurological development up through the last follow-up at 4.5 years. To date, the most effective strategy to prevent vertical CMV transmission is hygiene counseling for women of childbearing age, which, in our case, and in concordance with recent literature, applies to seronegative, as well as seropositive, women. Once an expecting mother shows seroconversion or signs of an active CMV infection, there are no established procedures to reduce the risk of transmission, or therapeutic options for the fetus with signs of infection. After birth, symptomatic infants can be treated with ganciclovir to inhibit viral replication and improve hearing ability and neurodevelopmental outcome. A comprehensive review of the literature, including our case study, reveals the most current and significant diagnostic and treatment options available. In conclusion, the triad of maternal hygiene counseling, postnatal hearing screening of all newborns, followed by CMV PCR in symptomatic infants, and antiviral therapy of infants with symptomatic cCMV provides an outline of best practice to reduce the burden of CMV transmission sequelae.