Hemoglobinuria for the early identification of STEC-HUS in high-risk children: data from the ItalKid-HUS Network.

Hemolytic uremic syndrome (HUS) represents one of the main causes of severe acute kidney injury in children. The most frequent form of HUS is caused by Shiga toxin-2 (Stx2)-producing Escherichia coli. Hemoglobinuria and hematuria are markers of glomerular damage, but their use has never been validated in HUS. We retrospectively analyzed the presence of hemoglobinuria/urinary red blood cells (RBCs) in children with Stx2-positive bloody diarrhea (BD) or with already ongoing STEC-HUS with the aim of validating its role in early identifying HUS. We reviewed all the pediatric patients with Stx2+ BD (group 1) and with ongoing HUS (group 2) referred to our center from 2010 to 2019. A total of 100 children were eligible for the study. In group 1, 22 patients showed hemoglobinuria/hematuria, while 41 remained negative. In 15/22 positive patients (68.2%), blood tests ruled in HUS, while in 7 (31.8%), HUS was excluded. Among the 41 patients persistently negative for hemoglobinuria/hematuria, no one developed HUS. The 37 STEC-HUS children (group 2) all had hemoglobinuria/RBCs at admission.Conclusion: Hemoglobinuria/hematuria for the diagnosis of HUS in children with Stx2+ BD showed a sensitivity of 100% and a specificity of 85%. We strongly recommend patients with BD carrying Stx2 in stools to be closely monitored with urine dipstick/urinalysis to early identify HUS. What is Known • Children with bloody diarrhea secondary to Shiga toxin 2 are at high risk of hemolytic uremic syndrome, thus have to be carefully monitored for the development of the disease, in order to early be hospitalized and treated. What is New • Urine dipstick for hemoglobinuria can be used as an easy, inexpensive, and repeatable tool to early diagnose children with bloody diarrhea secondary to Shiga toxin 2 to have developed hemolytic uremic syndrome, with no risk of false-negative results.

Capone V ，Mancuso MC ，Tamburini G ，Montini G ，Ardissino G ... -  《-》

Bloody Diarrhea and Shiga Toxin-Producing Escherichia coli Hemolytic Uremic Syndrome in Children: Data from the ItalKid-HUS Network.

To analyze the results of an enhanced laboratory-surveillance protocol for bloody diarrhea aimed at identifying children with Shiga toxin-producing Escherichia coli (STEC) infection early in the course of the disease toward the early identification and management of patients with hemolytic uremic syndrome (HUS). The study (2010-2019) involved a referral population of 2.3 million children. Stool samples of patients with bloody diarrhea were screened for Shiga toxin (Stx) genes. Positive patients were rehydrated and monitored for hemoglobinuria until diarrhea resolved or STEC-HUS was diagnosed. A total of 4767 children were screened; 214 (4.5%) were positive for either Stx1 (29.0%) or Stx2 (45.3%) or both Stx1+2 (25.7%); 34 patients (15.9%) developed STEC-HUS (0.71% of bloody diarrheas). Hemoglobinuria was present in all patients with HUS. Patients with Stx2 alone showed a greater risk of STEC-HUS (23.7% vs 12.7%) and none of the patients with Stx1 alone developed HUS. During the same period of time, 95 other patients were diagnosed STEC-HUS but were not captured by the screening program (26 had nonbloody diarrhea, 11 came from areas not covered by the screening program, and 58 had not been referred to the screening program, although they did meet the inclusion criteria). At HUS presentation, serum creatinine of patients identified by screening was significantly lower compared with that of the remaining patients (median 0.9 vs 1.51 mg/dL). Nearly 1% of children with bloody diarrhea developed STEC-HUS, and its diagnosis was anticipated by the screening program for Stx. The screening of bloody diarrhea for Stx is recommended, and monitoring patients carrying Stx2 with urine dipstick for hemoglobinuria is suggested to identify the renal complication as early as possible.

Ardissino G ，Vignati C ，Masia C ，Capone V ，Colombo R ，Tel F ，Daprai L ，Testa S ，Dodaro A ，Paglialonga F ，Luini M ，Brigotti M ，Picicco D ，Baldioli C ，Pagani F ，Ceruti R ，Tommasi P ，Possenti I ，Cresseri D ，Consonni D ，Montini G ，Arghittu M ，ItalKid-HUS Network ... -  《-》

Is Shigatoxin 1 protective for the development of Shigatoxin 2-related hemolytic uremic syndrome in children? Data from the ItalKid-HUS Network.

Ardissino G ，Possenti I ，Vignati C ，Daprai L ，Capone V ，Brigotti M ，Luini MV ，Consonni D ，Montini G ... -  《-》

An epidemiologic surveillance of Shiga-like toxin-producing Escherichia coli infection in Argentinean children: risk factors and serum Shiga-like toxin 2 values.

López EL ，Contrini MM ，Glatstein E ，Ayala SG ，Santoro R ，Ezcurra G ，Teplitz E ，Matsumoto Y ，Sato H ，Sakai K ，Katsuura Y ，Hoshide S ，Morita T ，Harning R ，Brookman S ... -  《-》

Case-management protocol for bloody diarrhea as a model to reduce the clinical impact of Shiga toxin-producing Escherichia coli infections. Experience from Southern Italy.

Loconsole D ，Giordano M ，Laforgia N ，Torres D ，Santangelo L ，Carbone V ，Parisi A ，Quarto M ，Scavia G ，Chironna M ，Bloody Diarrhea Apulia Working Group ... -  《-》