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Background Predicting disease severity can be informative for management of HUS. Dialysis requirement, volume depletion, elevated white blood cell counts, very young age, and use of antimotility agents are known factors associated with severe HUS. Methods A retrospective cohort analysis was performed to identify factors associated with dialysis duration using electronic medical record and chart review of 76 children [less than or equal to] 18 years of age at presentation with STEC-HUS identified through billing data from July 2008 to April 2020 at James Whitcomb Riley Hospital for Children, Indiana University, Indiana. Results Novel findings associated with prolonged dialysis duration were age [greater than or equal to] 6 years old at presentation (p = 0.041) and lack of drop in platelets below 60,000/mm.sup.3 anytime during the illness (p = 0.015). In addition, children with NSAID exposure trended longer on dialysis: 15 days with vs. 10 days without (p = 0.117). Known risk factors for severe disease including elevated peak white blood cell (WBC) count and higher hematocrit at presentation were also associated with longer dialysis duration: children with peak WBC > 20,000/mm.sup.3 were on dialysis for 15 vs. 9.5 days (p = 0.002) and in children on dialysis [greater than or equal to] 14 days hematocrit at presentation was 29.6% vs. 24.2% (p = 0.03). Children requiring dialysis for 20 days or longer were more likely to be on anti-hypertensive medications (p = 0.025) and have chronic kidney disease at 12-month follow up (p = 0.044). Conclusions Age [greater than or equal to] 6, elevated WBC count > 20,000/mm.sup.3, higher hematocrit at presentation, lack of drop in platelets to < 60,000/mm.sup.3, and possibly NSAID exposure during illness are associated with longer dialysis duration in STEC-HUS. Graphical abstract, Author(s): Myda Khalid [sup.1] , Chloe Miller [sup.1] , Netsanet Gebregziabher [sup.2] , Zoe Guckien [sup.1] , Shrea Goswami [sup.1] , Anthony Perkins [sup.2] , Sharon Phillips Andreoli [sup.1] Author [...]

Background Chronic kidney-related sequelae after STEC-HUS occur in 20-40% of patients. Hyperuricemia (HU) may cause acute and chronic toxicity involving the kidneys. We retrospectively assessed if there was an association between the presence of HU during the acute illness and that of kidney-related sequelae in children with STEC-HUS. Methods Children with STEC-HUS who had clinical and laboratory data at 2 years of follow-up were included in this case-control study. Univariate and multivariate analyses were performed between patients with (cases) or without (controls) kidney-related sequelae to identify factors associated with outcomes, including different measures of serum uric acid (sUA) (baseline level, peak, and duration of HU). HU was defined as sUA > 8 mg/dL. Results Of 86 patients included, 77.9% had HU. Patients with sequelae (n = 41) had a higher prevalence of HU (41/41 vs. 26/45, p < 0.01), higher baseline leukocyte count, serum creatinine (sCr), and sUA levels as well as lower sodium than controls. During hospitalization, cases also had higher sCr peak, sUA peak and duration of HU, requirement and duration of dialysis, extrarenal complications, and hypertension. By multivariate analysis, after adjusting for length of dialysis, only duration of HU (p = 0.0005; OR 1.7, 95% CI 1.27-2.36) remained as an independent predictor of sequelae, with a best cutoff of 5.5 days (AUC 0.95, specificity 80%, sensitivity 100%). Conclusions The presence of HU is a common finding in children with STEC-HUS and its duration during the acute stage was associated with kidney-related sequelae, regardless of the duration of dialysis. Graphical abstract, Author(s): Alejandro Balestracci [sup.1] , Luciana Meni Battaglia [sup.1] , Ismael Toledo [sup.1] , Laura Beaudoin [sup.1] , Sandra Mariel Martin [sup.1] , Nicolás Ariel Grisolía [sup.2] , Ronald J. [...]

Background The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011. Objective The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS. Data sources We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: 'Atypical Hemolytic Uremic Syndrome,' 'aHUS,' 'eculizumab,' 'Pediatrics,' 'Pediatric,' 'Child,' 'Children,' 'Adolescent.' Study eligibility criteria The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab. Participants and interventions The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment. Study appraisal For quality assessment, we used the Newcastle-Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Results The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab. Limitations The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes. Conclusions Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation. Systematic review registration number CRD42021266255., Author(s): Raquel Medeiros de Souza [sup.1] , Bernardo Henrique Mendes Correa [sup.1] , Paulo Henrique Moreira Melo [sup.1] , Pedro Antunes Pousa [sup.1] , Tamires Sara Campos de Mendonça [sup.1] [...]

Background The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. Methods We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin [less than or equal to] 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin [less than or equal to] 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. Results Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. Conclusion In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. Trial registration ClinicalTrials.gov identifier: NCT03776851. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Alejandro Balestracci [sup.1] , Marina Andrea Capone [sup.1] , Luciana Meni Battaglia [sup.1] , Ismael Toledo [sup.1] , Sandra Mariel Martin [sup.1] , Laura Beaudoin [sup.1] , Jeanette Balbaryski [...]

Background Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is the main cause of pediatric acute kidney injury (AKI) in Argentina. Endothelial injury is the trigger event in the microangiopathic process. The host inflammatory response to toxin and E. coli lipopolysaccharide (LPS) is involved in disease pathophysiology. Methods This retrospective study describes pediatric STEC-HUS patients with multiorgan involvement at the initial phase of disease. A retrospective study of critically ill HUS patients with evidence of E. coli infection was conducted through a period of 15 years. Results Forty-four patients 35.4 ± 4.1 months were admitted to the intensive care unit for 21 ± 2 days. Mechanical ventilation was required in 41 patients, early inotropic support in 37, and 28 developed septic shock. Forty-one patients required kidney replacement therapy for 12 ± 1 days. Forty-one patients showed neurological dysfunction. Dilated cardiomyopathy was demonstrated in 3 patients, left ventricular systolic dysfunction in 4, and hypertension in 17. Four patients had pulmonary hemorrhage, and acute respiratory distress syndrome in 2. Colectomy for transmural colonic necrosis was performed in 3 patients. Thirty-seven patients were treated with therapeutic plasma exchange, and 28 patients received methylprednisolone (10 mg/kg for 3 days). Of the surviving 32 patients, neurological sequelae were seen in 11 and chronic kidney failure in 5. Conclusions Severe clinical outcome at onset suggests an amplified inflammatory response after exposure to Shiga toxin and/or E. coli LPS. STEC-HUS associated with severe neurological involvement, hemodynamic instability, and AKI requires intensive care and focused therapy., Author(s): Mariana Luna [sup.1] , Mariana Kamariski [sup.1] , Iliana Principi [sup.1] , Victoria Bocanegra [sup.2] , Patricia G. Vallés [sup.1] [sup.3] Author Affiliations: (1) Servicio de Nefrología, Departamento de [...]

Background This study aimed to determine stroke incidence and assess the association between stroke and neurocognitive functioning in children with chronic kidney disease (CKD). Methods Data was derived from the Chronic Kidney Disease in Children (CKiD) cohort study. Stroke incidence was calculated after confirming self-reports of stroke occurrence by chart review. Each participant with stroke was matched with three stroke-free participants and performance on selected neurocognitive measures was compared. Wilcoxon rank-sum tests were used to compare neurocognitive test scores. Effect size (ES) was estimated using a modified version of Cohen's U.sub.3 metric that measures the excess percentage of the stroke group worse than the median of the control group. Results Of 891 subjects, five (0.56%) had a confirmed stroke prior to study entry. Median time at risk was 15.7 years [interquartile range, 12.5-18.4]. Estimated incidence rate of history of stroke was 36.8 per 100,000 children per year (95% confidence interval 15.3, 88.5). Controls and subjects with stroke were similar in age, CKD duration, race, and maternal education. ES for many of the neurocognitive comparisons was moderate to large. Subjects in the CKID cohort with a history of stroke had lower scores on spatial span reverse, spatial span forward, and design fluency, and worse parent ratings on BRIEF Metacognition Index compared to a matched sample of children with CKD without stroke. Conclusions Children with CKD have an increased incidence of prior ischemic stroke compared to the general pediatric population. A stroke history was associated with poorer performance on neurocognitive measures., Author(s): Juan C. Kupferman [sup.1] , Matthew B. Matheson [sup.2] , Marc B. Lande [sup.3] , Joseph T. Flynn [sup.4] , Susan Furth [sup.5] , Bradley A. Warady [sup.6] , [...]

Hemolytic uremic syndrome is commonly caused by Shiga toxin-producing Escherichia coli (STEC). Up to 15% of individuals with STEC-associated hemorrhagic diarrhea develop hemolytic uremic syndrome (STEC HUS). Hemolytic uremic syndrome (HUS) is a disorder comprising of thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. The kidney is the most commonly affected organ and approximately half of the affected patients require dialysis. Other organ systems can also be affected including the central nervous system and the gastrointestinal, cardiac, and musculoskeletal systems. Neurological complications include altered mental status, seizures, stroke, and coma. Gastrointestinal manifestations may present as hemorrhagic colitis, bowel ischemia/necrosis, and perforation. Pancreatitis and pancreatic beta cell dysfunction resulting in both acute and chronic insulin dependant diabetes mellitus can occur. Thrombotic microangiopathy (TMA) in cardiac microvasculature and troponin elevation has been reported, and musculoskeletal involvement manifesting as rhabdomyolysis has also been described. Extrarenal complications occur not only in the acute setting but may also be seen well after recovery from the acute phase of HUS. This review will focus on the extrarenal complications of STEC HUS. To date, management remains mainly supportive, and while there is no specific therapy for STEC HUS, supportive therapy has significantly reduced the mortality rate., Author(s): Myda Khalid [sup.1] , Sharon Andreoli [sup.1] Author Affiliations: (Aff1) grid.257413.6, 0000 0001 2287 3919, Riley Hospital for Children, Indiana University School of Medicine, , Indianapolis, IN, USA Introduction [...]

Haemolytic uraemic syndrome (HUS) remains a leading cause of paediatric acute kidney injury (AKI). Haemolytic uraemic syndrome is characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia and AKI. In ~ 90% of cases, HUS is a consequence of infection with Shiga toxin-producing E. coli (STEC), most commonly serotype O157:H7. Acute mortality from STEC-HUS is now less than 5%; however, there is significant long-term renal morbidity in one third of survivors. Currently, no specific treatment exists for STEC-HUS. There is growing interest in the role of complement in the pathogenesis of STEC-HUS due to the discovery of inherited and acquired dysregulation of the alternative complement system in the closely related disorder, atypical HUS (aHUS). The treatment of aHUS has been revolutionised by the introduction of the anti-C5 monoclonal antibody, eculizumab. However, the role of complement and anti-complement therapy in STEC-HUS remains unclear. Herein, we review the current evidence of the role of complement in STEC-HUS focusing on the use of eculizumab in this disease., Author(s): Patrick R. Walsh [sup.1] [sup.2] , Sally Johnson [sup.2] [sup.3] [sup.4] Author Affiliations: (Aff1) 0000 0001 0462 7212, grid.1006.7, Institute of Cellular Medicine, Newcastle University, , Newcastle upon Tyne, [...]

Background Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. The aim of the consensus meeting was to formulate guidelines for the diagnosis and management of HUS in children, specific to the needs of the country. Methods Four workgroups performed literature review and graded research studies addressing (i) investigations, biopsy, genetics, and differential diagnosis; (ii) Shiga toxin, pneumococcal, and infection-associated HUS; (iii) atypical HUS; and (iv) complement blockade. Consensus statements developed by the workgroups were discussed during a consensus meeting in March 2017. Results An algorithm for classification and evaluation was developed. The management of Shiga toxin-associated HUS is supportive; prompt plasma exchanges (PEX) is the chief therapy in patients with atypical HUS. Experts recommend that patients with anti-FH-associated HUS be managed with a combination of PEX and immunosuppressive medications. Indications for eculizumab include incomplete remission with plasma therapy, life-threatening features, complications of PEX or vascular access, inherited defects in complement regulation, and recurrence of HUS in allografts. Priorities for capacity building in regional and national laboratories are highlighted. Conclusions Limited diagnostic capabilities and lack of access to eculizumab prevent the implementation of international guidelines for HUS in most developing countries. We propose practice guidelines for India, which will perhaps be applicable to other developing countries., Author(s): Arvind Bagga [sup.1] , Priyanka Khandelwal [sup.1] , Kirtisudha Mishra [sup.2] , Ranjeet Thergaonkar [sup.3] , Anil Vasudevan [sup.4] , Jyoti Sharma [sup.5] , Saroj Kumar Patnaik [sup.6] , [...]

Background Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC). Methods TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab. Results The great clinical variability of brain injury in our cohort has led us to retrospectively build a 'neurological score' useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI). Conclusions A 'neurological score' may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach., Author(s): Paolo Giordano [sup.1] , Giuseppe Stefano Netti [sup.2] , Luisa Santangelo [sup.1] , Giuseppe Castellano [sup.3] , Vincenza Carbone [sup.1] , Diletta Domenica Torres [sup.1] , Marida Martino [sup.1] [...]

Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications: - terminal insufficiency of both organs, or - need for transplanting new liver as a source of lacking enzyme or specific regulator of the immune system in a patient with renal failure. A third (uncommon) option is secondary end-stage renal failure in liver transplant recipients. These three clinical settings use distinct qualification algorithms. The most common indications include primary hyperoxaluria type 1 (PH1) and autosomal recessive polycystic kidney disease (ARPKD), followed by liver diseases associated with occasional kidney failure. Availability of anti-C5a antibody (eculizumab) has limited the validity of CLKT in genetic atypical hemolytic uremic syndrome (aHUS). The liver coming from the same donor as renal graft (in CLKT) is immunologically protective for the kidney and this provides long-term rejection-free follow-up. No such protection is observed in SLKT, when both organs come from different donors, except uncommon cases of living donation of both organs. Overall long-term outcome in CLKT in terms of graft survival is good and not different from isolated liver or kidney transplantation, however patient survival is inferior due to complexity of this procedure., Author(s): Ryszard Grenda [sup.1] , Piotr Kalicinski [sup.2] Author Affiliations: (Aff1) 0000 0001 2232 2498, grid.413923.e, Department of Nephrology, Kidney Transplantation & Hypertension, The Children's Memorial Health Institute, , Warsaw, [...]

Introduction Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients. Methods We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database. Results A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria -1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost. Conclusion Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation., Author(s): Jesús Quintero Bernabeu [sup.1] , Javier Juamperez [sup.1] , Marina Muñoz [sup.2] , Olalla Rodriguez [sup.3] , Ramon Vilalta [sup.2] , José A. Molino [sup.4] , Marino Asensio [sup.4] [...]

Background Disorders of complement regulation are the most important etiology of atypical hemolytic uremic syndrome (aHUS). Recent studies demonstrate that eculizumab is beneficial in long-term aHUS treatment. We present a series of children with aHUS resistant to/dependent on plasma exchange (PE) who were treated with eculizumab. Methods This was a retrospective study in which data were retrieved from the medical files of children who had received PE as treatment for aHUS. The data retrieved included age, sex, presenting symptoms, presence of diarrhea/vomiting, hospitalization duration, laboratory data on admission and follow-up, need for transfusion or dialysis, response to PE, response to eculizumab and outcome. Results Of the 15 children diagnosed with aHUS in 2011 and 2012 in our departments, ten were resistant to, or dependent on, plasma therapy and treated with eculizumab; these children were enrolled in the study. Three patients had relapses, and seven had a new diagnosis. Nine children had oliguria or anuria, and eight required dialysis. Hypertension was observed in six patients. Neurologic involvement developed in six patients, with the symptoms including seizures, loss of balance, vision loss and severe confusion. Five and five patients were resistant to and dependent on plasma therapy, respectively. Following the start of eculizumab treatment, all patients achieved full recovery of renal function and hematologic parameters. Conclusions In our ten pediatric patients with aHUS who did not respond to PE, eculizumab was a lifesaving therapy and improved their quality of life. Early eculizumab use was a rescue therapy for renal function. Our results show that eculizumab is an effective treatment for aHUS. However, more studies are needed on the long-term efficacy and safety of eculizumab in children with aHUS and to determine the optimal duration of treatment., Author(s): Esra Baskin[sup.1] , Kaan Gulleroglu[sup.1] , Asli Kantar[sup.1] , Umut Bayrakci[sup.1] , Ozan Ozkaya[sup.2] Author Affiliations: (1) Pediatric Nephrology Department, Baskent University, 54. Cadde N:72/3, Bahcelievler, 06340, Cankaya, Ankara, [...]

Background To investigate the long-term neurodevelopmental outcome in children after hemolytic uremic syndrome (HUS) and to compare outcome dependent on central nervous system (CNS) involvement during HUS. Methods A single-center retrospective cohort of 47 children was examined at a median age of 10.6 (range 6-16.9) years and a median follow-up of 7.8 (range 0.4-15.3) years after having had HUS. Intellectual performance was assessed with the German version of the Wechsler Intelligence Scale 4th version and neuromotor performance with the Zurich Neuromotor Assessment (ZNA). The occurrence of neurological symptoms during the acute phase of HUS was evaluated retrospectively. Results Mean IQ of the whole study population fell within the normal range (median full scale IQ 104, range 54-127). Neuromotor performance was significantly poorer in the domains 'adaptive fine,' 'gross motor,' 'static balance' (all p < 0.05) and 'associated movements' (p < 0.001); only the 'pure motor' domain was within the normal reference range. Neurological findings occurred in 16/47 patients (34%) during acute HUS. Neurodevelopmental outcome was not significantly different between children with or without CNS involvement. Conclusions Our follow-up of children after HUS showed a favorable cognitive outcome. However, neuromotor outcome was impaired in all study participants. Neurological impairment during acute HUS was not predictive of outcome. Keywords Intellectual * Motor * Neurocognitive outcome * Central nervous system involvement * Hemolytic uremic syndrome, Introduction Hemolytic uremic syndrome (HUS) is a multi-organ and life-threatening disease characterized by hemolytic anemia, thrombocytopenia and acute renal injury. HUS is also one of the most frequent causes of [...]

Background Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) is a common thrombotic microangiopathy (TMA) in which central nervous system (CNS) involvement is responsible for the majority of deaths and for severe long-term sequelae. We have analyzed the role of hemoconcentration in disease severity. Methods This was a retrospective review of the records and laboratory data at presentation of all patients with STEC-HUS cases (n = 61) over a 10-year period. The patients were grouped into three severity classes: group A, comprising patients who did not require dialysis; group B, patients who were dialyzed without CNS involvement; group C, patients with CNS involvement. Results Patients with CNS involvement (group C) had a higher mean hemoglobin level (11.2 [+ or -] 2.3 g/dL) than those of group A or B (9.4 [+ or -] 2.1 and 7.5 [+ or -] 1.9 g/dL, respectively; p < 0.0001). We also observed that the higher the initial hemoglobin level, the more severe the long-term renal damage (p < 0.007). Conclusions In patients with STEC-HUS, hemoconcentration and hypovolemia may be responsible for more severe ischemic organ damage (both short and long term) at disease onset, and these signs should be regarded as risk factors for CNS damage and formore severe TMA. Therefore, we recommend that hydration status should be actively monitored in HUS patients and that dehydration, when diagnosed, should be promptly corrected. Keywords Diarrhea * Neurological involvement * Shigatoxin * Children * Hemolytic uremic syndrome, Introduction Hemolytic uremic syndrome (HUS), which is one of the most frequent causes of acute renal failure in children [1], is classically defined as the simultaneous occurrence of microangiopathic hemolytic [...]

Background Although erythropoietin (EPO) deficiency has been reported in children with post-diarrheal hemolytic uremic syndrome (D+HUS), very limited clinical data on EPO use in this disease are currently available. In this case-control study we examined whether EPO administration would reduce the number of red blood cell (RBC) transfusions in D+ HUS patients under our care. Methods Data from children treated exclusively with RBC transfusions (controls; n = 21) were retrospectively compared with data on those who also received EPO for the treatment of anemia (cases; n = 21). Results Both patient groups were similar in age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute phase severity was also comparable, as inferred by the need for dialysis (p = 0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81), presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children treated with EPO and two controls did not require any RBC transfusion (p = 1.00). Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52). Conclusion Treatment with EPO did not reduce the number of RBC transfusions in D+HUS children. Assessment of EPO efficacy in D+HUS merits further studies. Keywords Hemolytic uremic syndrome * Anemia * Erythropoietin * Red blood cell transfusion * Hemoglobin * Children, Introduction Microangiopathic hemolytic anemia is a hallmark of postdiarrheal hemolytic uremic syndrome (D+HUS) [1,2]. Inappropriately low levels of erythropoietin (EPO) relative to the severity of anemia have been demonstrated in [...]

Shiga toxin-associated haemolytic uraemic syndrome (Stx HUS) is the leading cause of paediatric acute kidney injury. This toxin-mediated disease carries a significant morbidity and mortality but has no direct treatments. Rare familial atypical HUS (aHUS) is now understood to result from over-activation of the alternative complement pathway causing glomerular endothelial damage. By understanding the pathogenic mechanisms of this disease, the monoclonal antibody eculizumab, which blocks the final common pathway of complement, is now being used to treat aHUS. For this reason, clinicians and scientists are studying the role of the alternative complement pathway in Stx HUS with the aim of targeting treatment in a similar way. There is some evidence suggesting that complement plays a role in the pathogenesis of Stx HUS, but other mechanisms may also be important. Clinically, modulating the complement system using plasma exchange provides no proven benefit in Stx HUS, and the use of eculizumab has provided conflicting results. Understanding the local effect of Stx on the glomerulus, in particular regulation of the complement and coagulation systems, may lead to advances in defining the precise pathogenesis of this disease. Then, targeted treatment strategies could be devised and clinical trials undertaken. Keywords Shiga toxin Complement* Haemolytic uraemic syndrome * Thrombotic microangiopathy * Eculizumab, Introduction Haemolytic uraemic syndrome (HUS) is a multi-system disease classically characterised by microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury [1-3]. Among the paediatric patient population, 90 % ofHUS cases [...]

Background The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. Methods Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. Results Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). Conclusions Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months. Keywords Hemolytic uremic syndrome * E. coli 0104:H4 * Children * Neurology * Outcome, Introduction Hemolytic uremic syndrome (HUS) is defined by the triad of hemolytic anemia, thrombocytopenia and acute kidney injury [1]. It is the most common cause of acute kidney injury during [...]

Simultaneous combined liver-kidney transplantation (CLKT) is a rare operation in pediatric patients so that annually only 10-30 operations are performed worldwide. The main indications for CLKT are primary hyperoxaluria type 1 and autosomal recessive polycystic kidney disease. In addition, CLKT is indicated in individual patients with metabolic or cirrhotic liver diseases and end-stage kidney disease. The surgery and immediate post-operative management of CLKT remain challenging in infants and small children. The patients should be operated on before they become severely ill or develop major systemic manifestations of their metabolic disorder. The liver allograft is immunologically protective of the kidney graft in simultaneous CLKT, often resulting in well-preserved kidney function. The long-term outcome after CLKT is nowadays comparable to that of isolated liver and kidney transplantations. Keywords Liver transplantation * Kidney transplantation * Children * Primary hyperoxaluria * Autosomal recessive polycystic kidney disease * Atypical hemolytic uremic syndrome, Introduction Combined liver-kidney transplantation (CLKT) is a two-step procedure, in which whole or partial liver and kidney from a donor are transplanted to a recipient in the same operation. The [...]

Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury (AKI). The outcomes of STEC HUS have improved, and the acute mortality rate in children is 1-4%. About 70 % of patients recover completely from the acute episode and the remainder have varying degrees of sequelae. Only a few retrospective studies have reviewed these patients over long periods. Methodological flaws include a lack of strict definitions, changing modes of treatment, ascertainment bias and loss of subjects to follow-up. The kidneys bear the brunt of the long-term damage: proteinuria (15-30 % of cases); hypertension (5-15 %); chronic kidney disease (CKD; 9-18 %); and end-stage kidney disease (ESKD; 3%). A smaller number have extra-renal sequelae: colonic strictures, cholelithiasis, diabetes mellitus or brain injury. Most renal sequelae are minor abnormalities, such as treatable hypertension and/or variable proteinuria. Most of the patients who progress to ESKD do not recover normal renal function after the acute episode. Length of anuria (more than 10 days) and prolonged dialysis are the most important risk factors for a poor acute and long-term renal outcome. After the acute episode all patients must be followed for at least 5 years, and severely affected patients should be followed indefinitely if there is proteinuria, hypertension or a reduced glomerular filtration rate (GFR). Keywords Hemolytic uremic syndrome * Long-term outcomes * Prognosis STEC HUS * D+HUS, Introduction The hemolytic uremic syndromes (HUS) are a major cause of acute kidney injury (AKI) in childhood and adults [1]. Before any causes were known, HUS was divided into diarrhea-associated [...]

Background Platelet transfusions should be avoided in children with post-diarrheal hemolytic uremic syndrome (D + HUS) because they might increase microthrombi formation, thereby aggravating the disease. As this possibility has not yet been explored, we investigated whether platelet transfusion in patients with D + HUS would lead to a worse disease course compared to that in patients who did not receive platelet transfusion. Methods This was a case-control study in which data from D + HUS children who received platelet transfusions (cases, n = 23) and those who did not (controls, n = 54) were retrospectively reviewed and compared. Results Both patient groups were similar in age (p=0.3), gender (p = 0.53), weight (p = 0.86), height (p = 0.45), prior use of non-steroidal anti-inflammatory drugs (p = 0.59) or antibiotics (p = 0.45) and presence of dehydration at admission (p = 0.79). The two groups also did not differ in initial leukocyte count (p = 0.98), hematocrit (p = 0.44) and sodium (p = 0.11) and alanine aminotransferase levels (p = 0.11). During hospitalization, dialysis duration (p = 0.08), number of erythrocyte transfusions (p = 0.2), serum creatinine peak (p = 0.22), presence of severe bowel (p = 0.43) or neurologic (p = 0.97) injury, arterial hypertension (p = 0.71), need for intensive care (p = 0.33) and death (p = 1.00) were also comparable. Conclusion Our findings suggest that platelet transfusion does not aggravate the course of the disease. Conversely, no hemorrhagic complications were observed in the group of patients who did not receive a platelet transfusion. Until these observations are confirmed by further studies, the benefits and risk of platelet transfusion should be thoughtfully balanced on an individual case basis. Keywords Hemolytic uremic syndrome * Thrombocytopenia * Platelet transfusion * Acute kidney injury * Clinical outcome, Introduction The primary pathological defect in post-diarrheal hemolytic uremic syndrome (D + HUS) is a thrombotic microangiopathy due to direct endothelial cell damage by the Shiga toxin, which results in [...]