Skip to main content

Advertisement

SpringerLink
Log in

Duration of prodromal phase and severity of hemolytic uremic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Some data have recognized an association between shorter prodromal phase and severe episode of Shiga toxin-producing Escherichia coli-related hemolytic uremic syndrome (STEC-HUS). Our aims were to confirm such association and analyze characteristics of STEC-HUS patients according to duration of the prodromal phase.

Methods

Patients treated from 2000 to 2022 were compared according to the presence of severe (> 10 days of dialysis and/or extra-renal complications) or non-severe disease. Association between prodromal phase duration and disease severity was assessed by ROC curve and by classifying the cohort in 3 groups according to time to diagnosis.

Results

Non-severe (n = 145) and severe (n = 71) cases were compared. The latter had shorter prodromal phase, higher leukocyte count, hemoglobin, lactic dehydrogenase, liver enzymes, C-reactive protein, urea and creatinine, and lower albumin and sodium; only prodromal phase duration (p = 0.02) and leukocyte count (p = 0.02) remained significant in multivariate analysis. By ROC curve analysis, time to diagnosis resulted in a poor predictor of outcomes (AUC = 0.27). Since prodromal phase duration was 5 days (IQR 3–7), we divided the cohort into Groups A (1–2 days), B (3–7 days), and C (≥ 8 days). Rates of severe disease were 75.8%, 29.6%, and 11.4%, respectively. Taking Group B as reference, Group A patients had higher risk of complications (p = 0.00001; OR 7.4, 95% CI: 2.98–18.7) while Group C ones had significantly less risk (p = 0.02; OR 0.3, 95% CI: 0.1–0.91).

Conclusions

This study found that duration of prodromal phase is an independent predictor of complicated STEC-HUS and confirms that shorter prodromal phase is associated with worse prognosis.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data are available from the corresponding author on reasonable request.

References

  1. Alconcher LF, Coccia PA, Suarez ADC, Monteverde ML, Perez Y, Gutiérrez MG, Carlopio PM, Missoni ML, Balestracci A, Principi I, Ramírez FB, Estrella P, Micelli S, Leroy DC, Quijada NE, Seminara C, Giordano MI, Hidalgo Solís SB, Saurit M, Caminitti A, Arias A, Rivas M, Risso P, Liern M (2018) Hyponatremia: a new predictor of mortality in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome. Pediatr Nephrol 33:1791–1798. https://doi.org/10.1007/s00467-018-3991-6

    Article  PubMed  Google Scholar 

  2. Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS (2013) Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 28:2097–2105. https://doi.org/10.1007/s00467-012-2383-6

    Article  PubMed  Google Scholar 

  3. Wong W, Prestidge C, Dickens A, Ronaldson J (2023) Diarrhoea-associated haemolytic uraemic syndrome and Shiga toxin-producing Escherichia coli infections in New Zealand children: clinical features and short-term complications from a 23-year cohort study. J Paediatr Child Health 59:493–498. https://doi.org/10.1111/jpc.16332

    Article  PubMed  Google Scholar 

  4. Ardissino G, Daccò V, Testa S, Civitillo CF, Tel F, Possenti I, Belingheri M, Castorina P, Bolsa-Ghiringhelli N, Tedeschi S, Paglialonga F, Salardi S, Consonni D, Zoia E, Salice P, Chidini G (2015) Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome. Pediatr Nephrol 30:345–352. https://doi.org/10.1007/s00467-014-2918-0

    Article  PubMed  Google Scholar 

  5. Mody RK, Gu W, Griffin PM, Jones TF, Rounds J, Shiferaw B, Tobin-D’Angelo M, Smith G, Spina N, Hurd S, Lathrop S, Palmer A, Boothe E, Luna-Gierke RE, Hoekstra RM (2015) Postdiarrheal hemolytic uremic syndrome in United States children: clinical spectrum and predictors of in-hospital death. J Pediatr 166:1022–1029. https://doi.org/10.1016/j.jpeds.2014.12.064

    Article  PubMed  Google Scholar 

  6. Tarr PI (2009) Shiga toxin-associated hemolytic uremic syndrome and thrombotic thrombocytopenic purpura distinct mechanisms of pathogenesis. Kidney Int Suppl 112:29–32. https://doi.org/10.1038/ki.2008.615

    Article  CAS  Google Scholar 

  7. Eid R, Bakr A, Elmougy A, Zedan MM, Allam NA, Sarhan A, Hammad A, El-Refaey AM, Hamdy N (2020) Postdiarrheal hemolytic uremic syndrome in Egyptian children: an 11-year single-center experience. Saudi J Kidney Dis Transpl 31:1376–1387. https://doi.org/10.4103/1319-2442.308349

    Article  PubMed  Google Scholar 

  8. Ardissino G, Tel F, Possenti I, Testa S, Consonni D, Paglialonga F, Salardi S, Borsa-Ghiringhelli N, Salice P, Tedeschi S, Castorina P, Colombo RM, Arghittu M, Daprai L, Monzani A, Tozzoli R, Brigotti M, Torresani E (2016) Early volume expansion and outcomes of hemolytic uremic syndrome. Pediatrics 137(1). https://doi.org/10.1542/peds.2015-2153

  9. Cobeñas CJ, Lombardi LL, Pereyra P, De Rose E, Gogorza MJ, Spizzirri AP, Ruscasso JD, Ferradas SL, Suárez ÁDC, Amoreo OR, Zalba JH, Risso P (2021) Hypoalbuminemia: a risk factor in patients with STEC-associated hemolytic uremic syndrome. Pediatr Nephrol 36:2739–2746. https://doi.org/10.1007/s00467-021-05017-8

    Article  PubMed  Google Scholar 

  10. Ninchoji T, Nozu K, Nakanishi K, Horinouchi T, Fujimura J, Yamamura T, Minamikawa S, Ishimori S, Nakanishi K, Yoshikawa N, Morioka I, Kaito H, Iijima K (2017) Clinical characteristics and long-term outcome of diarrhea-associated hemolytic uremic syndrome: a single center experience. Clin Exp Nephrol 21:889–894. https://doi.org/10.1007/s10157-016-1376-3

    Article  PubMed  Google Scholar 

  11. Ardissino G, Possenti I, Tel F, Testa S, Paglialonga F (2014) Time to change the definition of hemolytic uremic syndrome. Eur J Intern Med 25:e29. https://doi.org/10.1016/j.ejim.2013.12.002

    Article  PubMed  Google Scholar 

  12. Ministerio de Salud de la Nación Argentina. Boletín Integrado de Vigilancia. N° 477 – SE 50 – 2019. https://www.argentina.gob.ar/sites/default/files/201912-biv_477.pdf. Accessed 20 Mar 2023

  13. 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 (2021) Bloody diarrhea and Shiga toxin-producing Escherichia coli hemolytic uremic syndrome in children: data from the ItalKid-HUS network. J Pediatr 237:34-40.e1. https://doi.org/10.1016/j.jpeds.2021.06.048

    Article  PubMed  Google Scholar 

  14. Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE (2012) Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children. Pediatr Nephrol 27:1407–1410. https://doi.org/10.1007/s00467-012-2158-0

    Article  PubMed  Google Scholar 

  15. Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE (2014) Laboratory predictors of acute dialysis in hemolytic uremic syndrome. Pediatr Int 56:234–239. https://doi.org/10.1111/ped.12245

    Article  CAS  PubMed  Google Scholar 

  16. Nathanson S, Kwon T, Elmaleh M, Charbit M, Launay EA, Harambat J, Brun M, Ranchin B, Bandin F, Cloarec S et al (2010) Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 5:1218–1228. https://doi.org/10.2215/CJN.08921209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rahman RC, Cobeñas CJ, Drut R, Amoreo OR, Ruscasso JD, Spizzirri AP, Suarez Adel C, Zalba JH, Ferrari C, Gatti MC (2012) Hemorrhagic colitis in postdiarrheal hemolytic uremic syndrome: retrospective analysis of 54 children. Pediatr Nephrol 27:229–233. https://doi.org/10.1007/s00467-011-1973-z

    Article  PubMed  Google Scholar 

  18. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis (2005) International pediatric sepsis consensus conference defnitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8

    Article  PubMed  Google Scholar 

  19. Srinath AI, Lowe ME (2013) Pediatric pancreatitis. Pediatr Rev 34:79–90. https://doi.org/10.1542/pir.34-2-79

    Article  PubMed  Google Scholar 

  20. Suri RS, Clark WF, Barrowman N, Mahon JL, Thiessen-Philbrook HR, Rosas-Arellano MP, Zarnke K, Garland JS, Garg AX (2005) Diabetes during diarrhea-associated hemolytic uremic syndrome: a systematic review and meta-analysis. Diabetes Care 28:2556–2562. https://doi.org/10.2337/diacare

    Article  PubMed  Google Scholar 

  21. Ake JA, Jelacic S, Ciol MA, Watkins SL, Murray KF, Christie DL, Klein EJ, Tarr PI (2005) Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion. Pediatrics 115:e673-680. https://doi.org/10.1542/peds.2004-2236

    Article  PubMed  Google Scholar 

  22. Hickey CA, Beattie TJ, Cowieson J, Miyashita Y, Strife CF, Frem JC, Peterson JM, Butani L, Jones DP, Havens PL, Patel HP, Wong CS, Andreoli SP, Rothbaum RJ, Beck AM, Tarr PI (2011) Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome. Arch Pediatr Adolesc Med 165:884–889. https://doi.org/10.1001/archpediatrics.2011.152

    Article  PubMed  PubMed Central  Google Scholar 

  23. Loos S, Oh J, van de Loo L, Kemper MJ, Blohm M, Schild R (2021) Hemoconcentration and predictors in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS). Pediatr Nephrol 36:3777–3783. https://doi.org/10.1007/s00467-021-05108-6

    Article  PubMed  PubMed Central  Google Scholar 

  24. Oualha M, Pierrepont S, Krug P, Gitiaux C, Hubert P, Lesage F, Salomon R (2018) Postdiarrheal hemolytic and uremic syndrome with severe multiorgan involvement and associated early risk factors. Arch Pediatr 25:118–125. https://doi.org/10.1016/j.arcped.2017.12.005

    Article  CAS  PubMed  Google Scholar 

  25. Luna M, Kamariski M, Principi I, Bocanegra V, Vallés PG (2021) Severely ill pediatric patients with Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) who suffered from multiple organ involvement in the early stage. Pediatr Nephrol 36:1499–1509. https://doi.org/10.1007/s00467-020-04829-4

    Article  PubMed  Google Scholar 

  26. Shimizu M, Kuroda M, Inoue N, Konishi M, Igarashi N, Taneichi H, Kanegane H, Ito M, Saito S, Yachie A (2014) Extensive serum biomarker analysis in patients with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome. Cytokine 66:1–6. https://doi.org/10.1016/j.cyto.2013.12.005

    Article  CAS  PubMed  Google Scholar 

  27. Kamioka I, Yoshiya K, Satomura K, Kaito H, Fujita T, Iijima K, Nakanishi K, Yoshikawa N, Nozu K, Matsuo M, Japanese Society for Pediatric Nephrology (2008) Risk factors for developing severe clinical course in HUS patients: a national survey in Japan. Pediatr Int 50:441–446. https://doi.org/10.1111/j.1442-200X.2008.02605.x

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nephrology Unit, Hospital General de Niños Pedro de Elizalde, Montes de Oca 40, CP 1270, Ciudad Autónoma de Buenos Aires, Argentina

    Alejandro Balestracci, Luciana Meni Battaglia, Ismael Toledo, Sandra Mariel Martin & Laura Beaudoin

Authors
  1. Alejandro Balestracci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luciana Meni Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ismael Toledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandra Mariel Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura Beaudoin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alejandro Balestracci.

Ethics declarations

Ethics approval

The study was performed in accordance with the ethical standards of the institutional research and ethics committee (9543/23).

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Graphical abstract (PPTX 70 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balestracci, A., Meni Battaglia, L., Toledo, I. et al. Duration of prodromal phase and severity of hemolytic uremic syndrome. Pediatr Nephrol 39, 213–219 (2024). https://doi.org/10.1007/s00467-023-06104-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-023-06104-8

Keywords

Search

Navigation