Abstract
Background
Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae.
Methods
Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis.
Results
A total of 66% (n = 91, 95% CI 0.57–0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27–0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05).
Conclusions
Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome.
Graphical abstract
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Hemolytic uremic syndrome (HUS) is defined by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Infections with enterohemorrhagic Escherichia coli (EHEC) and subsequent translocation of Shiga toxin from the gut into the blood stream is the leading cause of HUS in childhood, termed STEC-HUS for Shiga toxin-producing E. coli or eHUS [1]. Many studies on the pathogenesis, epidemiology, and clinical presentation of STEC-HUS have been conducted, as it is a common cause of AKI [2].
Long-term prognosis of STEC-HUS was thought to be benign, even though 2/3 of patients need kidney replacement therapy (KRT) during the acute phase. However, prospective studies on the long-term outcome of STEC-HUS are scant and recommendations on follow-up are missing.
We present the results of a large multicenter prospective study on the outcome of pediatric STEC-HUS 10 years after the acute phase of disease. The initial study comprised 619 children with HUS. We previously reported clinical data on the acute phase and 5-year follow-up of this cohort [3, 4]. After 5 years, 70% of STEC-infected patients presented with no sequelae but 30% had proteinuria (18%), persistent hypertension (9%), decreased glomerular filtration rate (7%), and/or neurological symptoms (4%), interestingly, in 18% hypertension and proteinuria manifested during the follow-up period, indicating a possibility of developing kidney symptoms after complete resolution and hence a need for long-term follow-up. The aim of this study was to evaluate the long-term outcome of children with STEC-HUS 10 years after the acute phase and to identify risk factors for long-term sequelae.
Methods
Case definition
This prospective multicenter study included all patients admitted with the diagnosis of HUS in 27 participating children’s hospitals in Austria and Germany from January 1997 to December 2002 (participating centers listed below). Written informed consent was obtained from all subjects’ parents or guardians and agreement from all subjects wherever possible. Review board approval was obtained in the context of application for funding from the Federal Ministry for Education and Research, Germany (BMBF).
Clinical presentation and laboratory criteria resulted in the diagnosis of HUS, regardless of the cause of disease. Disease onset was defined as the day on which the following events were first recorded: hemolytic anemia (hemoglobin level < 10 g/dL) with microscopic evidence of fragmentocytes, thrombocytopenia (platelet count < 150 × 109 platelets/L), and AKI (serum creatinine concentration above the upper normal limit for age).
Study data
A standardized questionnaire requested clinical and laboratory data for the acute phase and for 1-, 2-, 3-, 5-, and 10-year follow-up assessments and was completed by the treating physicians [4].
The presence of at least one of the following criteria was used to define poor long-term outcome: hypertension (defined as systolic or diastolic blood pressure higher than the 95th percentile for age and gender [5]), neurological abnormalities (seizures, stroke, or impaired development), impaired kidney function (estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2, Schwartz formula [6]), or proteinuria (positive dip-sticks or > 150 mg/g creatinine).
Stool was tested for the presence of STEC using 3 sensitive assays [7, 8]. STEC-HUS was defined by the presence of one of the following criteria: (1) STEC isolation from stool and serotype determination, (2) evidence of Shiga toxin (stx) genes or antigens by either polymerase chain reaction or enzyme immunoassay, and/or (3) detection of antibodies against E. coli lipopolysaccharide (LPS) in serum by immunoblot (limited to O157). Using these criteria, we were able to divide patients into 2 groups—those with confirmed STEC infection and patients without evidence of STEC.
Statistical analysis
Categorical data are presented as percentages with absolute numbers and were compared using Fisher’s-exact and chi-square tests. Confidence intervals of 95% (95% CI) were calculated using the Clopper/Pearson method. Continuous data are shown as medians and interquartile ranges and compared using Mann–Whitney-U-test and Kruskal–Wallis-test according to distribution. Multivariate logistic regression analysis, using a stepwise forward variable selection procedure, included variables with p values < 0.2 in univariate analyses and was used to identify factors associated with poor long-term outcome. Two-tailed p values < 0.05 were considered statistically significant. A receiver operating characteristic (ROC) curve with determination of AUROC (area under the ROC) was plotted for specific laboratory parameters. Data analyses were performed with SPSS (version 29) for Windows (IBM Corp, Armonk, NY).
Results
Study population
A total of 619 HUS cases were included in the study during the acute phase of disease. Data on the acute phase and 5-year follow-up were previously published [3, 4]. Despite great efforts for gathering the data of all patients after 10 years, loss to follow-up rates were high, and for this analysis, only 27% (n = 170) of cases were available. Age and gender distribution remained stable over the follow-up period. A total of 82% of available cases (n = 138, CI 0.79–0.91) were identified as STEC-related. For this analysis, only the 138 confirmed STEC-HUS patients were included. Demographic data are presented in Table 1.
Outcome
After 10 years, 66% (n = 91, 95% CI 0.57–0.73) of the 138 patients had no symptoms reported. However, 34% (n = 47, 95% CI 0.27–0.43) were diagnosed to have either hypertension, proteinuria, impaired kidney function, and/or neurological problems. Thirty (64%) patients with sequelae presented with kidney symptoms for the first time 1 year after the acute disease, two after 2 years, three after 3 years, three after 5 years (1.5/year), and nine for the first time 10 years after acute disease (1.8/year) (Fig. 1). A total of 95% (n = 43, 95% CI 0.88–1) of patients presenting symptoms at the 10-year follow-up required KRT during acute phase of disease.
The presence of hypertension, proteinuria, and/or reduced eGFR at 1-year follow-up was significantly associated with the presence of kidney symptoms 10 years after acute disease (all p = 0.001). Interestingly, 36% (n = 17) of patients with no problems at 1-year follow-up developed kidney symptoms at the 10-year follow-up (Fig. 1).
Median eGFR after 10 years was 94.3 mL/min/1.73 m2 (IQR 80.0–104.3). Twenty-seven patients (24%, CI 0.17–0.32) presented with eGFR < 80 mL/min/1.73 m2, all of whom required KRT during the acute phase for a median of 14 days (IQR 6–26). Kidney abnormalities after 10 years are detailed in Table 2.
Patients not needing KRT during the acute phase of disease (n = 22) had eGFR > 80 mL/min/1.73 m2 after 10 years, 1 presented proteinuria, and 1 hypertension during the follow-up period. No patient in this group presented symptoms after apparent recovery.
Hypertension was present at the 10-year follow-up in 17% (n = 20, 95% CI 0.11–0.24). Of those patients with hypertension after 10 years, 13% had no hypertension reported in the acute phase (n = 11, 95% CI 0.07–0.22). Eight percent of completely recovered patients at 1 year had hypertension reported after 10 years (n = 6, CI 95% 0.03–0.17).
Proteinuria was present in 23% at the 10-year follow-up (n = 26, CI 95% 0.16–0.32). A total of 57% of them presented with proteinuria already at the 1-year follow-up (n = 13, CI 95% 0.23–0.58), and the rest developed proteinuria in the follow-up period (2 at 2-year, 2 at 5-year, and 9 at the 10-year follow-up). From completely recovered patients after 1 year, 13% presented with proteinuria after 10 years (n = 9, CI 95% 0.06–0.21), all of them with eGFR > 80 mL/min/1.73 m2. Proteinuria persisted over the 10-year follow-up period in 39% (n = 13, CI 95% 0.22–0.56) once diagnosed at the 1-year follow-up.
A total of 2% of all STEC-positive patients underwent kidney transplantation (n = 10, CI 95% 0.8–3.4): one patient within the first year after acute disease, three after 1 year, three after 2 years, and three after 5 years. Median age at presentation was 2.8 years (IQR 1.3–10.2), and all of them required KRT in the acute phase.
Factors affecting long-term outcome
We found a significant association between the presence of bloody diarrhea, need for KRT, KRT duration and treatment with therapeutic plasma exchange (TPE) (all p < 0.05), and the availability of data for the 10-year follow-up. This indicates that the patients who were available for follow-up were the ones who were more severely ill in the acute phase (Table 1).
Univariate analysis suggested several risk factors for long-term sequelae; information is detailed in Table 3. The need for KRT during the acute phase was associated with the composite endpoint of any sequelae after 10 years in the patients available for analysis (p < 0.001). Patients presenting with sequelae needed KRT for a median of 17 days (IQR 12–26) and completely recovered patients for a median of 9 days (IQR 7–15) (p < 0.001). The use of plasma treatment was also associated with the presence of sequelae after 10 years (p < 0.001).
Multivariate logistic regression analyses identified the use of plasma therapy (p = 0.032, OR 7.6 95% CI 1.2–49) and the duration of KRT (p = 0.009, OR 1.127 95% CI 1.03–1.24) as the most significant predictors for long-term sequelae, confirming the findings of our previous report [3].
We found no association between hemoglobin (Hb) levels at admission (AUROC 0.54, 95% CI 0.43–0.64) or LDH (AUROC 0.48, 95% CI 0.37–0.59) and sequelae at the 10-year follow-up. Additionally, no association with poor long-term outcome could be identified in our cohort using the severity score proposed by Ardissino et al. (Hb + 2 × sCr) (AUROC 0.61, 95% CI 0.50–0.71) [9].
Discussion
Kidney disease in childhood is associated with higher risk of developing chronic kidney disease (CKD) and kidney failure in adulthood. Early identification of patients at increased risk of developing CKD might reduce the incidence of manifest kidney disease in adulthood by implementation of early interventions [10]. STEC-HUS, in contrast to atypical HUS, is known as an acute disease followed by complete recovery in most cases. Our study shows that patients who were apparently fully recovered after acute disease are still at risk of developing kidney symptoms after at least 10 years. Thus, a potentially increased risk of CKD in adulthood may be underestimated.
Moreover, new reports on follow-up of children with AKI for all causes, including HUS, have shown that these patients show increased mortality and healthcare utilization and are at higher risk of adverse long-term outcomes, including CKD, proteinuria, and hypertension [11, 12].
This study presents the data of 138 confirmed STEC-HUS patients followed for a period of 10 years after acute disease. Despite the large rate of dropout after 10 years, this is one of the largest long-term follow-up cohorts of confirmed STEC-positive HUS cases. A total of 34% of patients presented with symptoms after 10 years.
Previous reports on long-term outcome of HUS show diverse results. A systematic review by Garg et al. reports long-term sequelae in 0 to 60% of cases after 4 years (range 1–22 years) [13]. Other reports show results that are comparable to ours with proteinuria, hypertension, and decreased creatinine clearance/eGFR in 39% of cases after 9.6 years (some appearing after a period of apparent recovery) [14], 25% of patients after 10 years [15], 23% after 5 years [16], 44% after 8.7 years [17], or 26% after 4 years [18]. Overall, dropout rates for follow-up were high and patients available for long-term follow-up were more critically ill in the acute phase. Therefore, the overall prevalence of long-term kidney abnormalities is probably lower than what is reported in our study and in the literature. The fact that, after 10 years, only a small proportion of patients from the initial cohort was available for follow-up and that the available patients were the ones who were more severely ill during the acute phase may lead to an overestimation of patients with kidney symptoms, which is a relevant limitation of this study.
This prospective multicenter study confirms that the duration of anuria/KRT, reflecting the severity of kidney injury in the acute phase, is the strongest predictive factor for poor long-term outcome [14, 16, 19,20,21]. Despite hypertension, neurological symptoms, and leukocytosis being described as risk factors for poor outcome in our and in other previous reports [3, 13], these were not associated with poor outcome at 10 years. No association between development of kidney symptoms and previously described risk factors such as age, use of antibiotics, or STEC serogroup was found 5 years after acute disease [3, 15, 22]. These factors also showed no influence on the outcome after 10 years.
In a previous report, the analysis of follow-up up to 5 years after the acute disease showed that patients who are apparently fully recovered 1 year after acute disease are still at risk of developing sequelae later [3]. A total of 36% of patients with no symptoms at 1-year follow-up developed symptoms within 5 to 10 years after STEC-HUS, indicating that apparent completely recovered patients are still at risk of developing proteinuria, hypertension, or reduced eGFR. Our study confirms that the absence of hypertension, proteinuria, and/or reduced eGFR at 1-year follow-up can only poorly predict the development of kidney symptoms 10 years after acute disease. A French study similarly showed that the absence of kidney abnormalities such as proteinuria, hypertension, or low eGFR after 1 year could only poorly predict the course of kidney function over a long-term period as 33% of patients developed kidney abnormalities beyond the 1-year follow-up [17]. Analogous results were observed in a German cohort, with one-sixth of patients with no signs of kidney injury at 1-year follow-up presenting kidney abnormalities at a later examination [23]. A recent study identified symptoms for the first time 10 years after acute disease in 15% of patients progressing to CKD after STEC-HUS [24]. Therefore, our findings and recent reports in the literature disagree with previous studies which suggest that follow-up could be restricted to patients presenting with symptoms 1 year after the acute disease [25]. Due to the lack of data on rates of proteinuria and/or hypertension in healthy children, we were not able to compare our follow-up results of patients with STEC HUS. Another limitation of our study is the fact that orthostatic proteinuria was not recorded as well as comorbidities such as obesity, and therefore, the number of patients with proteinuria could be overestimated.
Although many efforts have been made to develop tools for predicting a severe course of the acute disease and presence of sequelae, the severity of kidney injury during the acute phase remained the most relevant predictor of poor long-term outcome in our cohort. Recently reported tools use hemoglobin, LDH, and creatinine levels to calculate the risk for development of severe acute disease [9, 26, 27]. When we applied this score retrospectively to our cohort, no association with the presence of kidney symptoms after 10 years was observed.
Treatment of STEC-HUS is supportive. However, a recent prospective, randomized, placebo-controlled study evaluated the efficacy of eculizumab during the acute phase of disease in pediatric STEC-HUS patients and suggests that this treatment could reduce the risk for long-term kidney abnormalities 1 year after acute disease [28]. This evaluation was not possible in our cohort, since eculizumab was not yet available during the time the acute clinical data was gathered.
The high dropout rate of HUS survivors in this study might demonstrate the lack of adequate follow-up of these children. Recent reports on children requiring KRT for all causes of AKI have shown that less than 1/3 of these patients have been seen by a pediatric nephrologist, while the majority have been followed-up by general pediatricians [29]. Better guidelines on post-AKI follow-up for general practitioners are needed as they could improve long-term outcomes.
In conclusion, the severity of kidney impairment during the acute phase of disease remains the most relevant predictor for developing symptoms over a 10-year period. STEC-HUS patients should be screened at least yearly for hypertension, proteinuria, and kidney function for at least 10 years after the acute disease, especially if they needed KRT during the acute phase of disease, as they are still at risk of developing kidney symptoms, even after a period of apparent total recovery.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
References
Würzner R, Riedl M, Rosales A, Orth-Höller D (2014) Treatment of enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome (eHUS). Semin Thromb Hemost 40:508–516
Michael M, Bagga A, Sartain SE, Smith RJH (2022) Haemolytic uraemic syndrome. Lancet 400:1722–1740
Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, Strasak A, Orth-Höller D, Würzner R, Karch H, German-Austrian HUS Study Group (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
Gerber A, Karch H, Allerberger F, Verweyen HM, Zimmerhackl LB (2002) Clinical course and the role of shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients, 1997–2000, in Germany and Austria: a prospective study. J Infect Dis 186:493–500
Wühl E, Witte K, Soergel M, Mehls O, Schaefer F, German Working Group on Pediatric Hypertension (2002) Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens 20:1995–2007
Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263
Friedrich AW, Bielaszewska M, Zhang WL, Pulz M, Kuczius T, Ammon A, Karch H (2002) Escherichia coli harboring Shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis 185:74–84
Karch H, Tarr PI, Bielaszewska M (2005) Enterohaemorrhagic Escherichia coli in human medicine. Int J Med Microbiol 295:405–418
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, Network ItalKid-HUS (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
Calderon-Margalit R, Skorecki K, Vivante A (2018) History of childhood kidney disease and risk of adult end-stage renal disease. N Engl J Med 378:1751–1752
Robinson CH, Jeyakumar N, Luo B, Wald R, Garg AX, Nash DM, McArthur E, Greenberg JH, Askenazi D, Mammen C, Thabane L, Goldstein S, Parekh RS, Zappitelli M, Chanchlani R (2021) Long-term kidney outcomes following dialysis-treated childhood acute kidney injury: a population-based cohort study. J Am Soc Nephrol 32:2005–2019
Greenberg JH, Coca S, Parikh CR (2014) Long-term risk of chronic kidney disease and mortality in children after acute kidney injury: a systematic review. BMC Nephrol 15:184
Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, Clark WF (2003) Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA 290:1360–1370
Siegler RL, Milligan MK, Burningham TH, Christofferson RD, Chang SY, Jorde LB (1991) Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome. J Pediatr 118:195–200
Gianviti A, Tozzi AE, De Petris L, Caprioli A, Ravà L, Edefonti A, Ardissino G, Montini G, Zacchello G, Ferretti A, Pecoraro C, De Palo T, Caringella A, Gaido M, Coppo R, Perfumo F, Miglietti N, Ratsche I, Penza R, Capasso G, Maringhini S, Li Volti S, Setzu C, Pennesi M, Bettinelli A, Peratoner L, Pela I, Salvaggio E, Lama G, Maffei S, Rizzoni G (2003) Risk factors for poor renal prognosis in children with hemolytic uremic syndrome. Pediatr Nephrol 18:1229–1235
Hüseman D, Gellermann J, Vollmer I, Ohde I, Devaux S, Ehrich JH, Filler G (1999) Long-term prognosis of hemolytic uremic syndrome and effective renal plasma flow. Pediatr Nephrol 13:672–677
Monet-Didailler C, Godron-Dubrasquet A, Madden I, Delmas Y, Llanas B, Harambat J (2019) Long-term outcome of diarrhea-associated hemolytic uremic syndrome is poorly related to markers of kidney injury at 1-year follow-up in a population-based cohort. Pediatr Nephrol 34:657–662
Ylinen E, Salmenlinna S, Halkilahti J, Jahnukainen T, Korhonen L, Virkkala T, Rimhanen-Finne R, Nuutinen M, Kataja J, Arikoski P, Linkosalo L, Bai X, Matussek A, Jalanko H, Saxén H (2020) Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli in children: incidence, risk factors, and clinical outcome. Pediatr Nephrol 35:1749–1759
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, Müller D, Härtel 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
Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS (2013) Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 28:2097–2105
Oakes RS, Kirkham JK, Kirkhamm JK, Nelson RD, Siegler RL (2008) Duration of oliguria and anuria as predictors of chronic renal-related sequelae in post-diarrheal hemolytic uremic syndrome. Pediatr Nephrol 23:1303–1308
Orth D, Grif K, Khan AB, Naim A, Dierich MP, Wurzner R (2007) The Shiga toxin genotype rather than the amount of Shiga toxin or the cytotoxicity of Shiga toxin in vitro correlates with the appearance of the hemolytic uremic syndrome. Diagn Microbiol Infect Dis 59:235–242
Vaterodt L, Holle J, Hüseman D, Müller D, Thumfart J (2018) Short- and long-term renal outcome of hemolytic-uremic syndrome in childhood. Front Pediatr 6:220
Alconcher LF, Lucarelli LI, Bronfen S (2023) Long-term kidney outcomes in non-dialyzed children with Shiga-toxin Escherichia coli associated hemolytic uremic syndrome. Pediatr Nephrol 38:2131–2136
Small G, Watson AR, Evans JH, Gallagher J (1999) Hemolytic uremic syndrome: defining the need for long-term follow-up. Clin Nephrol 52:352–356
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
Meni Battaglia L, Balestracci A (2022) A novel prognostic index in hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli. Pediatr Nephrol 37:463–464
Garnier A, Brochard K, Kwon T, Sellier-Leclerc AL, Lahoche A, Launay EA, Nobili F, Caillez M, Taque S, Harambat J, Michel-Bourdat G, Guigonis V, Fila M, Cloarec S, Djamal-Dine D, de Parscaux L, Allard L, Salomon R, Ulinski T, Frémeaux-Bacchi V, Morin C, Olivier-Abbal P, Colineaux H, Auriol F, Arnaud C, Kieffer I, Brusq C (2023) Efficacy and safety of eculizumab in pediatric patients affected by Shiga toxin-related hemolytic and uremic syndrome: a randomized, placebo-controlled trial. J Am Soc Nephrol 34:1561–1573
Hessey E, Morissette G, Lacroix J, Perreault S, Samuel S, Dorais M, Phan V, Jouvet P, Lafrance JP, LeLorier J, Palijan A, Pizzi M, Roy L, Zappitelli M (2018) Healthcare utilization after acute kidney injury in the pediatric intensive care unit. Clin J Am Soc Nephrol 13:685–692
Acknowledgements
We thank all contributing physicians, nurses, clinical personnel, pediatric centers, and laboratories for collaboration and input in this study:
Austria: St. Josef Hospital, Braunau; Dept. of Pediatrics, Medical Univ. of Graz; Dept. of Pediatrics, Medical Univ. of Innsbruck; Dept. of Pediatrics, Medical Univ. of Vienna.
Germany: Dept. of Pediatrics, Charité Berlin; “Links der Weser” Clinic, Bremen; Dept. of Pediatrics, Univ. of Erlangen; Dept. of Pediatrics, Univ. of Essen; KfH Pediatric Kidney Center, Frankfurt; Centre for Children’s Health, Univ. Clinic Freiburg; Altona Hospital, Hamburg; Dept. of Pediatrics, Univ. Medical Center Hamburg-Eppendorf; Dept. of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School; Dept. of Pediatrics, Univ. of Heidelberg; Dept. of Pediatrics, Univ. of Jena; Dept. of Pediatrics and Adolescent Medicine, Köln Univ. Hospital; Univ. Children´s Clinic, Kiel; St. Georg City Clinic, Leipzig; Dept. of Pediatrics, Univ. of Mainz; KfH Pediatric Kidney Center, Marburg; Dept. of Pediatric Nephrology, Children’s Hospital Memmingen; Schwabing Hospital Children Clinic, Munich; Univ. Children’s Clinic, Münster; Pediatric Nephrology, Univ. Children’s Hospital, Rostock; Univ. Children’s Clinics Schleswig-Holstein, Campus Lübeck; Dept. of Pediatrics, Olga Hospital, Stuttgart; Reinhard Nieter Hospital, Children’s clinic, Wilhelmshaven.
Funding
Open access funding provided by University of Innsbruck and Medical University of Innsbruck. This work was supported by the following institutions and grants: German Society of Pediatric Nephrology; EU Biomed-2 (program PL-950970); Federal Ministry for Research and Education (project 01K19905), Germany; European Society of Pediatric Nephrology; Nationalbank Jubiläumsfond Austria (projects 12711 and 13655); FWF-funded doctoral program HOROS (W1253); and Medical University of Innsbruck, Austria.
Author information
Authors and Affiliations
Consortia
Contributions
Study conception and design: A.R., M.R.K., and R.W.; data collection: S.K.; analysis and interpretation of results: A.R., M.R.K., and R.W.; draft manuscript preparation: A.R.; review and editing: A.R., T.G., J.H., M. R.K., D.O.-H., W.B., G.C., T.J., and R.W. All authors reviewed the results and approved the final version of the manuscript.
Corresponding author
Ethics declarations
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.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Rosales, A., Kuppelwieser, S., Giner, T. et al. Outcome 10 years after Shiga toxin-producing E. coli (STEC)-associated hemolytic uremic syndrome: importance of long-term follow-up. Pediatr Nephrol 39, 2459–2465 (2024). https://doi.org/10.1007/s00467-024-06355-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-024-06355-z