A simple prognostic index for Shigatoxin-related hemolytic uremic syndrome at onset: data from the ItalKid-HUS network
Shigatoxin Escherichia coli-related hemolytic uremic syndrome (eHUS) is a severe thrombotic microangiopathy (TMA) burdened by life-threatening complications and long-term sequelae. Since hemoconcentration is associated with worse outcome, we tried to develop a reliable and easy-to-calculate index for predicting complications and sequelae based on hemoglobin (Hb) at presentation. The first laboratory examinations with signs of TMA in eHUS patients were analyzed in relation to the outcomes with the receiver operating characteristic curves and their areas under the curve (AUC) for Hb and creatinine (sCr). A total of 197 eHUS patients were identified of whom 24% did not have anemia at presentation. Hb level was the best predictor of a poor outcome (AUC 0.67) but the combination of Hb with sCr, in the formula [(Hb in g/dL + (sCr in mg/dL × 2)], showed an even better AUC of 0.75. The described scoring system was also strongly associated and predictive of all complications and health care needs (8% of patients with scoring > 13 died or entered a permanent vegetative state compared with 0% of those with ≤ 13).
What is Known:
• In eHUS, hemoconcentration is associated with worse short- and long-term outcome.
• A prognostic index to identify patients at higher risk for complications at presentation is not available.
What is New:
• We developed a simple and early prognostic index for eHUS outcome with the combination of Hb and sCr at onset, in the following formula [(Hb in g/dL + (sCr in mg/dL × 2)].
• The proposed HUS Severity Score can promptly identify patients with good outcome and those with high risk of worse short- and long-term outcome.
KeywordsHemolytic uremic syndrome Prognostic index Shigatoxin Escherichia coli infection Thrombotic microangiopathy
Area under the curve
Chronic kidney disease
Estimated glomerular filtration rate
eHUS Severity Score
Shigatoxin Escherichia coli-related hemolytic uremic syndrome
Receiver operating characteristic
Renal replacement therapy
Shiga Toxin E. Coli
The following members of the ItalKid-HUS Network, to whom we are particularly thankful, gave an essential contribution to the present study: P. Accorsi (Pieve di Coriano), N. Altamura (Sesto San Giovanni), S. Andreoni (Novara), C. Baldioli (Cittiglio), B. Balduzzi (Esine), A. Bonazza (Brescia), A. Bonomini (Melzo), G. Bossi (Pavia), E. Cama (Desenzano del Garda), P. Carlucci (Milano), M. Casciana (Mantova), D. Casnaghi (Rho), R. Celano (Milano), R. Ceruti (Mantova), M. Facchini (Milano), C. Giacomazzi (Aosta), V. Goj (Milano), S. Grossi (Brescia), S. Maiandi (Lodi), ML. Melzi (Monza), E. Milanesi (Cremona), A. Monzani (Novara), A. Negri (Varese), B. Osnaghi (Magenta), F. Pagani (Brescia), L. Parola (Magenta), P. Pedroni (Manerbio), A. Pellegatta (Busto Arsizio), I. Possenti (Alessandria), A. Reciputo (Cinisello Balsamo), B. Roman (Vimercate), A. Rosco (Garbagnate), F. Salvini (Milano), S. Sardini (Asola), C. Sciuto (Lecco), M. Silvestri (Verbania), P. Tommasi (Milano), and C. Zambetti (Lodi). We would like to thank PROGETTO ALICE–ASSOCIAZIONE PER LA LOTTA ALLA SEU for their support and continuous commitment to our research.
Dr. Ardissino performed data collection, analyzed the data, drafted the initial manuscript, and revised and approved the final version.
Dr. Tel, Testa, Paglialonga, Consolo, and Chidini designed the data collection instruments, performed data collection, revised the article, and approved the final version.
Dr. Longhi, Martelli, Picicco, Dodaro, and Daprai performed data collection, edited, revised, and approved the final version.
Dr. Colombo, Arghittu, Perrone, and Scalia Catenacci performed data collection, analyzed the data, revised the article, and approved the final version.
Dr. Consonni analyzed the data and performed the statistical analysis.
No support/funding is present in this paper.
Compliance with ethical standards
The Ethics Committee of our hospital was informed about the study, which was conducted in accordance with our institution’s ethical regulations.
Conflicts of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
- 2.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 CrossRefPubMedGoogle Scholar
- 3.Ardissino G, Salardi S, Colombo E, Testa S, Borsa-Ghiringhelli N, Paglialonga F, Paracchini V, Tel F, Possenti I, Belingheri M, Civitillo CF, Sardini S, Ceruti R, Baldioli C, Tommasi P, Parola L, Russo F, Tedeschi S (2016) Epidemiology of haemolytic uremic syndrome in children. Data from the north Italian HUS network. Eur J Pediatr 175:465–473. https://doi.org/10.1007/s00431-015-2642-1 CrossRefPubMedGoogle Scholar
- 4.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.2015-2153. CrossRefGoogle Scholar
- 5.Ardissino G, Tel F, Picicco D, Dodaro A, Daprai L, Consolo S, Testa S, Paglialonga F, Consonni D, ItalKid HUS Network (2018) Comment on “blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome” by Keenswijk et al. Eur J Pediatr 2017;176(3): 355-360. Eur J Pediatr 177:269–270. https://doi.org/10.1007/s00431-017-2989-6 CrossRefPubMedGoogle Scholar
- 7.Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, Clarck WF (2003) Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA 290:1360–1370. https://doi.org/10.1001/jama.290.10.1360 CrossRefPubMedGoogle Scholar
- 8.Keenswijk W, Vanmassenhove J, Raes A, Dhont E, Vande Walle J (2017) Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome, a preliminary study. Eur J Pediatr 176:355–360. https://doi.org/10.1007/s00431-016-2846-z CrossRefPubMedGoogle Scholar
- 9.Loos S, Ahlenstiel T, Kranz B, Staude H, Pape L, Härtel C, Vester U, Buchtala L, Benz K, Hoppe B, Beringer O, Krause M, Müller D, Pohl M, Lemke J, Hillebrand G, Kreuzer M, König 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/cis531 CrossRefPubMedGoogle Scholar
- 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 166:1022102–1022109. https://doi.org/10.1016/j.jpeds.2014.12.064 CrossRefGoogle Scholar
- 13.Ojeda JM, Kohout I, Cuestas E (2013) Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome. Nefrologia 33:372–376. https://doi.org/10.3265/Nefrologia.pre2012.Nov.11648. PubMedGoogle Scholar