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Review
. 2025 Feb;40(2):449-461.
doi: 10.1007/s00467-024-06480-9. Epub 2024 Sep 30.

Shiga toxin-producing Escherichia coli infection as a precipitating factor for atypical hemolytic-uremic syndrome

Gabriele Mortari  1   2   3 , Carolina Bigatti  1   4 , Giulia Proietti Gaffi  4 , Barbara Lionetti  4 , Andrea Angeletti  1 , Simona Matarese  4 , Enrico Eugenio Verrina  1 , Gianluca Caridi  1 , Francesca Lugani  5 , Valerio Gaetano Vellone  6 , Decimo Silvio Chiarenza  1   4 , Edoardo La Porta  1
Affiliations
Review

Shiga toxin-producing Escherichia coli infection as a precipitating factor for atypical hemolytic-uremic syndrome

Gabriele Mortari et al. Pediatr Nephrol. 2025 Feb.

Abstract

Background: Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis. It can be classified as either typical, primarily caused by Shiga toxin-producing Escherichia coli (STEC) infection, or as atypical HUS (aHUS), which results from uncontrolled complement activation.

Methods: We report the case of a 9-year-old boy with aHUS due to compound heterozygous complement factor H-related genes (CFHR) 1/3 and CFHR1-CFHR4 deletions, leading to the development of anti-complement factor H (CFH) autoantibodies. The patient presented nephrological and neurological thrombotic microangiopathy with STEC positivity. Additionally, we provide an extensive literature review of aHUS cases initially classified as typical.

Results: A total of 11 patients were included, 73% of whom were pediatric. Kidney replacement therapy was required in 73% of patients. The recurrence rate was 55%. All cases were found positive for pathological variants of the complement system genes. The most commonly implicated gene was CFH, while the CFHR genes were involved in 36% of cases, although none exhibited anti-CFH autoantibodies. Anti-complement therapy was administered in 54% of cases, and none of the patients who received it early progressed to kidney failure.

Conclusions: STEC infection does not exclude aHUS diagnosis, and early use of anti-complement therapy might be reasonable in life-threatening conditions. Genetic testing can be helpful in patients with atypical presentations and can confirm the necessity of prolonged anti-complement therapy.

Keywords: Anti-CFH antibody; Anti-complement therapy; Atypical HUS; CFHR; Eculizumab; STEC-HUS.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

Figures

None
A higher resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
Timeline of the most important clinical events. On the upper graph, trends in biochemical parameters are reported. Below, the most important clinical and laboratory findings are reported. CKRT, continuous kidney replacement therapy; IHD, intermittent hemodialysis; LDH, lactate dehydrogenase; HUS, hemolytic uremic syndrome; ADAMST13, a disintegrin and metalloproteinase with thrombospondin type 1 motif member 13; STEC, Shiga toxin-producing Escherichia coli; CFH, complement factor H; CFHR, complement factor H-related genes; Abs, antibodies
Fig. 2
Fig. 2
Flow chart of the methodology used to screen the articles. Ten articles published between 2008 and 2023 were included in the review
See this image and copyright information in PMC

References

    1. Sakari Jokiranta T, Viklicky O, Al Shorafa S et al (2017) Differential diagnosis of thrombotic microangiopathy in nephrology. BMC Nephrol 18:324. 10.1186/s12882-017-0727-y - PMC - PubMed
    1. Connell NT, Cheves T, Sweeney JD (2016) Effect of ADAMTS13 activity turnaround time on plasma utilization for suspected thrombotic thrombocytopenic purpura. Transfusion (Paris) 56:354–359. 10.1111/trf.13359 - PubMed
    1. Nester CM, Barbour T, de Cordoba SR et al (2015) Atypical aHUS: state of the art. Mol Immunol 67:31–42. 10.1016/j.molimm.2015.03.246 - PubMed
    1. Mody RK, Gu W, Griffin PM et al (2015) Postdiarrheal hemolytic uremic syndrome in United States children: clinical spectrum and predictors of in-hospital death. J Pediatr 166:1022–1029. 10.1016/j.jpeds.2014.12.064 - PubMed
    1. Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS (2013) Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 28:2097–2105. 10.1007/s00467-012-2383-6 - PubMed

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