Hemolytic-uremic syndrome classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2], Anila Hussain, MD [3]Parth Vikram Singh, MBBS[4]

Overview

HUS may be classified as typical (caused by Shiga-toxin producing E. coli/ Shigella infection) or atypical (caused by complement factor abnormalities, other viral or bacterial infections, HIV, malignancy, organ transplantation, and rarely SLE and pregnancy related).

HUS is commonly discussed within the broader category of thrombotic microangiopathy. In this framework,^[1] atypical HUS denotes a primary thrombotic microangiopathy caused by dysregulation of the complement system, whereas STEC-associated HUS is a secondary thrombotic microangiopathy triggered by microbial factors that activate endothelial cells and initiate the microangiopathic cascade.

Classification

Hemolytic-uremic syndrome (HUS) may be classified as follows:

Typical Or Diarrhea Related

Shiga toxin producing E. Coli/ Shigella infection

Atypical or Non Diarrheal

Primary Causes

Complement factor abnormalities
- Complement factor H (CFH) mutation/ factor H deficiency (autosomal dominant)^[2]
- Complement factor I (CFI) deficiency (acquired antibody mediated)^[3]^[4]
- Membrane co-factor protein deficiency (MCP, CD46)^[5]^[6]
- Factor B overactivity (complement factor B mutation)^[7]
- Diacylglycerol kinase epsilon gene mutations^[8]

Secondary Causes

Infection
- Pneumococcal infection (commonly pneumonia, empyema, meningitis, and less commonly pericarditis, peritonitis, otitis media, and bacteremia)^[9]
- HIV
- Other viral or bacterial infections
Drug associated
Malignancy
Pregnancy^[10]
Organ transplantation
Other medical conditions( antiphospholipid syndrome, scleroderma, lupus)

References

↑ Freedman SB, van de Kar NC, Tarr PI (October 2023). “Shiga Toxin-Producing Escherichia coli and the Hemolytic-Uremic Syndrome”. N Engl J Med. 389 (15): 1402–1414. doi:10.1056/NEJMra2108739. PMID 37819955 Check |pmid= value (help).
↑ Dragon-Durey MA, Frémeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G; et al. (2004). “Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases”. J Am Soc Nephrol. 15 (3): 787–95. PMID 14978182.
↑ Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, Vigneau C, Kuypers D, Boudailliez B; et al. (2004). “Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome”. J Med Genet. 41 (6): e84. PMC 1735822. PMID 15173250.
↑ Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G; et al. (2005). “Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome”. J Am Soc Nephrol. 16 (7): 2150–5. doi:10.1681/ASN.2005010103. PMID 15917334.
↑ Fang CJ, Fremeaux-Bacchi V, Liszewski MK, Pianetti G, Noris M, Goodship TH; et al. (2008). “Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome”. Blood. 111 (2): 624–32. doi:10.1182/blood-2007-04-084533. PMC 2200836. PMID 17914026.
↑ Fremeaux-Bacchi V, Moulton EA, Kavanagh D, Dragon-Durey MA, Blouin J, Caudy A; et al. (2006). “Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome”. J Am Soc Nephrol. 17 (7): 2017–25. doi:10.1681/ASN.2005101051. PMID 16762990.
↑ Marinozzi MC, Vergoz L, Rybkine T, Ngo S, Bettoni S, Pashov A; et al. (2014). “Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign?”. J Am Soc Nephrol. 25 (9): 2053–65. doi:10.1681/ASN.2013070796. PMC 4147975. PMID 24652797.
↑ Zhu J, Chaki M, Lu D, Ren C, Wang SS, Rauhauser A; et al. (2016). “Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production”. Am J Physiol Renal Physiol. 310 (9): F895–908. doi:10.1152/ajprenal.00431.2015. PMC 4867310. PMID 26887830.
↑ Copelovitch, L. & Kaplan, B.S. Pediatr Nephrol (2008) 23: 1951. https://doi.org/10.1007/s00467-007-0518-y
↑ Fakhouri F, Roumenina L, Provot F, Sallée M, Caillard S, Couzi L; et al. (2010). “Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations”. J Am Soc Nephrol. 21 (5): 859–67. doi:10.1681/ASN.2009070706. PMC 2865741. PMID 20203157.

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[pmid37819955-1] Freedman SB, van de Kar NC, Tarr PI (October 2023). “Shiga Toxin-Producing Escherichia coli and the Hemolytic-Uremic Syndrome”. N Engl J Med. 389 (15): 1402–1414. doi:10.1056/NEJMra2108739. PMID 37819955 Check |pmid= value (help).

[pmid14978182-2] Dragon-Durey MA, Frémeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G; et al. (2004). “Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases”. J Am Soc Nephrol. 15 (3): 787–95. PMID 14978182.

[pmid15173250-3] Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, Vigneau C, Kuypers D, Boudailliez B; et al. (2004). “Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome”. J Med Genet. 41 (6): e84. PMC 1735822. PMID 15173250.

[pmid15917334-4] Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G; et al. (2005). “Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome”. J Am Soc Nephrol. 16 (7): 2150–5. doi:10.1681/ASN.2005010103. PMID 15917334.

[pmid17914026-5] Fang CJ, Fremeaux-Bacchi V, Liszewski MK, Pianetti G, Noris M, Goodship TH; et al. (2008). “Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome”. Blood. 111 (2): 624–32. doi:10.1182/blood-2007-04-084533. PMC 2200836. PMID 17914026.

[pmid16762990-6] Fremeaux-Bacchi V, Moulton EA, Kavanagh D, Dragon-Durey MA, Blouin J, Caudy A; et al. (2006). “Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome”. J Am Soc Nephrol. 17 (7): 2017–25. doi:10.1681/ASN.2005101051. PMID 16762990.

[pmid24652797-7] Marinozzi MC, Vergoz L, Rybkine T, Ngo S, Bettoni S, Pashov A; et al. (2014). “Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign?”. J Am Soc Nephrol. 25 (9): 2053–65. doi:10.1681/ASN.2013070796. PMC 4147975. PMID 24652797.

[pmid26887830-8] Zhu J, Chaki M, Lu D, Ren C, Wang SS, Rauhauser A; et al. (2016). “Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production”. Am J Physiol Renal Physiol. 310 (9): F895–908. doi:10.1152/ajprenal.00431.2015. PMC 4867310. PMID 26887830.

[9] Copelovitch, L. & Kaplan, B.S. Pediatr Nephrol (2008) 23: 1951. https://doi.org/10.1007/s00467-007-0518-y

[pmid20203157-10] Fakhouri F, Roumenina L, Provot F, Sallée M, Caillard S, Couzi L; et al. (2010). “Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations”. J Am Soc Nephrol. 21 (5): 859–67. doi:10.1681/ASN.2009070706. PMC 2865741. PMID 20203157.

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