Top

Pediatric Nephrology

Published in:

Open Access 19-01-2024 | Hemolytic Uremic Syndrome | Original Article

Volume expansion mitigates Shiga toxin-producing E. coli-hemolytic uremic syndrome in children

Authors: Johannes Böckenhauer, Raphael Schild, Markus J. Kemper, Thomas Henne, Marie V. Stein, Jun Oh, Sebastian Loos

Published in: Pediatric Nephrology | Issue 6/2024

Abstract

Background

Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS) is associated with high morbidity and relevant mortality. Previous small studies showed that volume expansion could improve the course and outcome of STEC-HUS. The aim of this single-center study was to evaluate the effect of volume expansion on the clinical course and outcome in STEC-HUS.

Methods

Data of pediatric patients with STEC-HUS were analyzed retrospectively. Course and outcome of patients treated with volume expansion (VE) from 2019 to 2022 (n = 38) were compared to historical controls (HC) from 2009 to 2018 (n = 111).

Results

Patients in the VE group had a significant relative median weight gain compared to HC (7.8% (3.4–11.3) vs. 1.2% (− 0.7–3.9), p < 0.0001) 48 h after admission. The need for dialysis was not reduced by VE (VE 21/38 (55.3%) vs. HC 64/111 (57.7%), p = 0.8). However, central nervous system involvement (impairment of consciousness, seizures, focal neurological deficits, and/or visual disturbances) was significantly reduced (VE 6/38 (15.8%) vs. HC 38/111 (34.2%), p = 0.039). None of the patients in the VE group died or developed chronic kidney disease (CKD) stage 5, whereas in the HC group, three patients died and three patients had CKD stage 5 at discharge.

Conclusions

This study suggests that volume expansion may be associated with the mitigation of the acute course of STEC-HUS, especially severe neurological involvement and the development of CKD. Prospective trials should lead to standardized protocols for volume expansion in children with STEC-HUS.

Graphical abstract

Available only for authorised users

Freedman SB, van de Kar N, Tarr PI (2023) Shiga toxin-producing Escherichia coli and the hemolytic-uremic syndrome. N Engl J Med 389:1402–1414. https://doi.org/10.1056/NEJMra2108739CrossRefPubMed

Exeni RA, Fernandez-Brando RJ, Santiago AP, Fiorentino GA, Exeni AM, Ramos MV, Palermo MS (2018) Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol 33:2057–2071. https://doi.org/10.1007/s00467-017-3876-0CrossRefPubMed

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/s00467-012-2383-6CrossRefPubMed

Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, Strasak A, Orth-Holler D, Wurzner R, Karch H (2012) Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis 54:1413–1421. https://doi.org/10.1093/cid/cis196CrossRefPubMed

Loos S, Aulbert W, Hoppe B, Ahlenstiel-Grunow T, Kranz B, Wahl C, Staude H, Humberg A, Benz K, Krause M, Pohl M, Liebau MC, Schild R, Lemke J, Beringer O, Muller D, Hartel C, Wigger M, Vester U, Konrad M, Haffner D, Pape L, Oh J, Kemper MJ (2017) Intermediate follow-up of pediatric patients with hemolytic uremic syndrome during the 2011 outbreak caused by E. coli O104:H4. Clin Infect Dis 64:1637–1643. https://doi.org/10.1093/cid/cix218CrossRefPubMed

Alconcher LF, Lucarelli LI, Bronfen S, Villarreal F (2023) Kidney sequelae in 281 Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome patients after a median follow-up of 12 years. Pediatr Nephrol. https://doi.org/10.1007/s00467-023-06183-7CrossRefPubMed

Grisaru S, Xie J, Samuel S, Hartling L, Tarr PI, Schnadower D, Freedman SB, Alberta Provincial Pediatric Enteric Infection Team (2017) Associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli: a systematic review and meta-analysis. JAMA Pediatr 171:68–76. https://doi.org/10.1001/jamapediatrics.2016.2952CrossRefPubMed

Ardissino G, Dacco 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 (2014) Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome. Pediatr Nephrol 30:345–352. https://doi.org/10.1007/s00467-014-2918-0CrossRefPubMed

Ardissino G, Tel F, Testa S, Paglialonga F, Longhi S, Martelli L, Consolo S, Picicco D, Dodaro A, Daprai L, Colombo R, Arghittu M, Perrone M, Chidini G, Scalia Catenacci S, Cropanese I, Consonni D; ItalKid-HUS Network (2018) A simple prognostic index for Shigatoxin-related hemolytic uremic syndrome at onset: data from the ItalKid-HUS network. Eur J Pediatr 177:1667–1674. https://doi.org/10.1007/s00431-018-3198-7CrossRefPubMed

10.

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.2014.12.064CrossRefPubMed

11.

McKee RS, Schnadower D, Tarr PI, Xie J, Finkelstein Y, Desai N, Lane RD, Bergmann KR, Kaplan RL, Hariharan S, Cruz AT, Cohen DM, Dixon A, Ramgopal S, Rominger A, Powell EC, Kilgar J, Michelson KA, Beer D, Bitzan M, Pruitt CM, Yen K, Meckler GD, Plint AC, Bradin S, Abramo TJ, Gouin S, Kam AJ, Schuh A, Balamuth F, Hunley TE, Kanegaye JT, Jones NE, Avva U, Porter R, Fein DM, Louie JP, Freedman SB, Pediatric Emergency Medicine Collaborative Research Committee and Pediatric Emergency Research Canada (2020) Predicting hemolytic uremic syndrome and renal replacement therapy in Shiga toxin-producing Escherichia coli-infected Children. Clin Infect Dis 70:1643–1651. https://doi.org/10.1093/cid/ciz432CrossRefPubMed

12.

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/s00467-012-2158-0CrossRefPubMed

13.

Oakes RS, Siegler RL, McReynolds MA, Pysher T, Pavia AT (2006) Predictors of fatality in postdiarrheal hemolytic uremic syndrome. Pediatrics 117:1656–1662. https://doi.org/10.1542/peds.2005-0785CrossRefPubMed

14.

Alconcher LF, Coccia PA, Suarez ADC, Monteverde ML, Perez YGMG, Carlopio PM, Missoni ML, Balestracci A, Principi I, Ramirez FB, Estrella P, Micelli S, Leroy DC, Quijada NE, Seminara C, Giordano MI, Hidalgo Solis 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/s00467-018-3991-6CrossRefPubMed

15.

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/s00467-021-05108-6CrossRefPubMedPubMedCentral

16.

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.2004-2236CrossRefPubMed

17.

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.2011.152CrossRefPubMedPubMedCentral

18.

Freedman SB, Schnadower D, Estes M, Casper TC, Goldstein SL, Grisaru S, Pavia AT, Wilfond BS, Metheney M, Kimball K, Tarr PI, Hyperhydration to Improve Kidney Outcomes in children with Shiga Toxin-producing E. Coli infection (HIKO-STEC) Study Team (2023) Hyperhydration to improve kidney outcomes in children with Shiga toxin-producing E. coli infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial). Trials 24:359. https://doi.org/10.1186/s13063-023-07379-wCrossRefPubMedPubMedCentral

19.

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 137:1–9. https://doi.org/10.1542/peds.2015-2153CrossRef

20.

Bonany P, Bilkis MD, Iglesias G, Braun A, Tello J, Ratto V, Vargas A, Koch E, Jannello P, Monteverde E (2021) Fluid restriction versus volume expansion in children with diarrhea-associated HUS: a retrospective observational study. Pediatr Nephrol 36:103–109. https://doi.org/10.1007/s00467-020-04673-6CrossRefPubMed

21.

Loos S, Ahlenstiel T, Kranz B, Staude H, Pape L, Hartel C, Vester U, Buchtala L, Benz K, Hoppe B, Beringer O, Krause M, Muller D, Pohl M, Lemke J, Hillebrand G, Kreuzer M, Konig J, Wigger M, Konrad M, Haffner D, Oh J, Kemper MJ (2012) An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. Clin Infect Dis 55:753–759. https://doi.org/10.1093/cid/cis531CrossRefPubMed

22.

Schwartz GJ, Gauthier B (1985) A simple estimate of glomerular filtration rate in adolescent boys. J Pediatr 106:522–526CrossRefPubMed

23.

Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral

24.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 3(Suppl):1–150

Title: Volume expansion mitigates Shiga toxin-producing E. coli-hemolytic uremic syndrome in children
Authors: Johannes Böckenhauer
Raphael Schild
Markus J. Kemper
Thomas Henne
Marie V. Stein
Jun Oh
Sebastian Loos
Publication date: 19-01-2024
Publisher: Springer Berlin Heidelberg
Keywords: Hemolytic Uremic Syndrome
Chronic Kidney Disease
Enterohemorrhagic Escherichia Coli
Published in: Pediatric Nephrology / Issue 6/2024
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-023-06276-3

At a glance: The STEP trials

Springer Medicine

Volume expansion mitigates Shiga toxin-producing E. coli-hemolytic uremic syndrome in children

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

Please log in to get access to this content

Other articles of this Issue 6/2024

Clearance and nutrition in neonatal continuous kidney replacement therapy using the Carpediem™ system

Eculizumab in STEC-HUS with severe neurological involvement: a New Zealand perspective

Urinary sphingolipids in adolescents and young adults with youth-onset diabetes

Use of a donor kidney with known autosomal dominant polycystic kidney disease in a highly sensitised paediatric recipient

Urinary tract infection guidelines should address unique, specific questions and include analyses of primary data

Childhood-onset IgA nephropathy: is long-term recovery possible?