Cause Of Hemolytic Uremic Syndrome Research Articles

Serogroups and Toxin Variants of Clinical Shiga Toxin-Producing Escherichia coli Strains Isolated from Patients with Hemolytic Uremic Syndrome in Turkey.

Shiga toxin-producing Escherichia coli (STEC) refers to a group of bacteria that can cause infections, which are common worldwide and pose a serious public health problem, as they can lead to conditions such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). HUS is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Determination of serogroups and toxin profiles of STEC is important for estimating their disease-causing potential and predicting epidemiological changes. This study analyzed STEC isolates from 46 pediatric HUS patients across Turkey, using polymerase chain reaction to determine O serogroups and Shiga toxin (Stx) variants from stool samples collected between 2016 and 2019. Of the patients, 25 (54.3%) were in the 0-2 age group. Of the isolates, 82.6% were non-O157 serogroup. The most detected serogroup was O145 (32.6%), and 28.3% of the serogroups were not typed. Of the strains, 8 (17.4%) had Stx1 alone, 26 (56.5%) had Stx2 alone, and 12 (26.1%) had both Stx1 and Stx2. The Stx variants occurred in seven combinations, with the most common being Stx2a alone (56.5%). The duration of hospitalization for patients with Stx2a was found to be longer than that for patients with other variants (p = 0.01). This study highlights a concerning trend in Turkey, where non-O157 serogroups, particularly O145, emerged as prevalent causes of HUS. The predominance of Stx2a among our isolates and the longer hospitalization duration for patients with Stx2a support findings linking this variant to severe clinical outcomes, including HUS. Understanding the dynamics of these Stx variants will help better prepare for and mitigate the impacts of STEC infections in our population.

Determinants of Sporadic Shiga Toxin-Producing Escherichia coli (STEC) Infection in Denmark, 2018-2020: A Matched Case-Control Study.

Infections with Shiga toxin-producing Escherichia coli (STEC) are increasing in Denmark and elsewhere. STEC is also the most frequent cause of haemolytic uraemic syndrome (HUS) in Danish children. Most cases are considered sporadic, while approximately one-third can be attributed to a known source of infection. Hence, we examined sources of sporadic STEC infection in Denmark. From January 2018 to December 2020, we conducted a prospective nationwide case-control study among Danish adults and children. Cases with confirmed positive STEC infection were notified infections within the national laboratory surveillance system. Control persons were randomly selected from the Danish Civil Registration System, individually matched in age in 5-year bands and sex. Participants were invited by an electronic letter to complete either an adult or child questionnaire online. Univariate and adjusted matched odds ratios were computed for adults and children using conditional logistic regression. The study recruited 1583 STEC cases and 6228 controls. A total of 658 cases (42%) and 2155 controls (35%) were included in the analysis. Depending on age, univariate analysis adjusted for socio-demographic determinants showed that the consumption of boiled beef (mOR = 2.2, 95% confidence interval (CI): 1.6-3.1) and fried minced beef (mOR = 1.6, CI: 1.2-2.1), drinking raw (unpasteurized) milk (mOR = 11, CI 1.1-110), eating grilled food (mOR = 9.8, CI: 5.6-17) and having a household member using diapers (mOR = 2.1, CI: 1.4-3.2) were determinants of sporadic STEC infection. Further multivariate adjusted analysis resulted in the same determinants. This study confirms that beef is an overall important risk factor for STEC infection in Denmark. We also present evidence that a proportion of sporadic STEC infections in Denmark are determined by age-specific eating habits, environmental exposures and household structure, rather than being exclusively food-related. These findings are relevant for targeted public health actions and guidelines.

Constipation and hemolytic uremic syndrome.

Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) classically presents with diarrhea. Absence of diarrheal prodrome increases suspicion for atypical HUS (aHUS). Inability to obtain a fecal specimen for culture or culture-independent testing limits the ability to differentiate STEC-HUS and aHUS. Our patient presented with abdominal pain and constipation, and evaluation of pallor led to a diagnosis of HUS. There was a complete absence of diarrhea during the disease course. Lack of fecal specimen for several days delayed testing for STEC. Treatment for atypical HUS was initiated with complement-blockade therapy. PCR-testing for Shiga toxin from fecal specimen later returned positive. Alternative complement-pathway testing did not identify a causative genetic variant or anti-Factor H antibody. A diagnosis of STEC-HUS was assigned, and complement-blockade therapy was stopped. Diagnosis of aHUS remains a diagnosis of exclusion, whereby other causes of HUS are eliminated with reasonable certainty. Exclusion of STEC is necessary and relies on testing availability and recognition of testing limitations. Diarrhea-negative STEC-HUS remains a minority of cases, and future research is needed to explore the clinical characteristics of these patients.

SARS-CoV-2 and Emerging Foodborne Pathogens: Intriguing Commonalities and Obvious Differences.

The coronavirus disease 2019 (COVID-19) has resulted in tremendous human and economic losses around the globe. The pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that is closely related to SARS-CoV and other human and animal coronaviruses. Although foodborne diseases are rarely of pandemic proportions, some of the causative agents emerge in a manner remarkably similar to what was observed recently with SARS-CoV-2. For example, Shiga toxin-producing Escherichia coli (STEC), the most common cause of hemolytic uremic syndrome, shares evolution, pathogenesis, and immune evasion similarities with SARS-CoV-2. Both agents evolved over time in animal hosts, and during infection, they bind to specific receptors on the host cell’s membrane and develop host adaptation mechanisms. Mechanisms such as point mutations and gene loss/genetic acquisition are the main driving forces for the evolution of SARS-CoV-2 and STEC. Both pathogens affect multiple body organs, and the resulting diseases are not completely cured with non-vaccine therapeutics. However, SARS-CoV-2 and STEC obviously differ in the nature of the infectious agent (i.e., virus vs. bacterium), disease epidemiological details (e.g., transmission vehicle and symptoms onset time), and disease severity. SARS-CoV-2 triggered a global pandemic while STEC led to limited, but sometimes serious, disease outbreaks. The current review compares several key aspects of these two pathogenic agents, including the underlying mechanisms of emergence, the driving forces for evolution, pathogenic mechanisms, and the host immune responses. We ask what can be learned from the emergence of both infectious agents in order to alleviate future outbreaks or pandemics.

Comparative Genomics of Shiga Toxin-Producing Escherichia coli Strains Isolated from Pediatric Patients with and without Hemolytic Uremic Syndrome from 2000 to 2016 in Finland.

ABSTRACTShiga toxin-producing Escherichia coli (STEC) infection can cause mild to severe illness, such as nonbloody or bloody diarrhea, and the fatal hemolytic uremic syndrome (HUS). The molecular mechanism underlying the variable pathogenicity of STEC infection is not fully defined so far. Here, we performed a comparative genomics study on a large collection of clinical STEC strains collected from STEC-infected pediatric patients with and without HUS in Finland over a 16-year period, aiming to identify the bacterial genetic factors that can predict the risk to cause HUS and poor renal outcome. Of 240 STEC strains included in this study, 52 (21.7%) were from pediatric patients with HUS. Serotype O157:H7 was the main cause of HUS, and Shiga toxin gene subtype stx2a was significantly associated with HUS. Comparative genomics and pangenome-wide association studies identified a number of virulence and accessory genes overrepresented in HUS-associated STEC compared to non-HUS STEC strains, including genes encoding cytolethal distending toxins, type III secretion system effectors, adherence factors, etc. No virulence or accessory gene was significantly associated with risk factors for poor renal outcome among HUS patients assessed in this study, including need for and duration of dialysis, presence and duration of anuria, and leukocyte counts. Whole-genome phylogeny and multiple-correspondence analysis of pangenomes could not separate HUS STEC from non-HUS STEC strains, suggesting that STEC strains with diverse genetic backgrounds may independently acquire genetic elements that determine their varied pathogenicity. Our findings indicate that nonbacterial factors, i.e., characteristics of the host immunity, might affect STEC virulence and clinical outcomes.IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is a serious public health burden worldwide which causes outbreaks of gastrointestinal diseases and the fatal hemolytic uremic syndrome (HUS) characterized by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal failure. Understanding the mechanism underlying the disease severity and patient outcome is of high importance. Using comparative genomics on a large collection of clinical STEC strains from STEC-infected patients with and without HUS, our study provides a reference of STEC genetic factors/variants that can be used as predictors of the development of HUS, which will aid risk assessment at the early stage of STEC infection. Additionally, our findings suggest that nonbacterial factors may play a primary role in the renal outcome in STEC-infected patients with HUS; further studies are needed to validate this.

Shiga Toxin 2a Induces NETosis via NOX-Dependent Pathway.

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS), one of the main causes of acute kidney injury in children. Stx plays an important role in endothelium damage and pathogenesis of STEC-HUS. However, the effects of Stx on neutrophils and neutrophil extracellular trap (NET) formation are not well understood. In this study, we investigated how Stx2a affects NET formation and NETotic pathways (NADPH or NOX-dependent and -independent) using neutrophils isolated from healthy donors and patients with STEC-HUS, during the acute and recovery phase of the disease. Stx2a dose-dependently induced NETosis in neutrophils isolated from both healthy controls and STEC-HUS patients. NETosis kinetics and mechanistic data with pathway-specific inhibitors including diphenyleneiodonium (DPI)-, ERK-, and P38-inhibitors showed that Stx2a-induced NETosis via the NOX-dependent pathway. Neutrophils from STEC-HUS patients in the acute phase showed less ROS and NETs formation compared to neutrophils of the recovery phase of the disease and in healthy controls. NETs induced by Stx2a may lead to the activation of endothelial cells, which might contribute to the manifestation of thrombotic microangiopathy in STEC-HUS.

Hemolytic Uremic Syndrome Following Influenza A (H1N1) pdm09 Virus in a 14-Month-Old Girl:

Hemolytic Uremic Syndrome (HUS) is characterized by the clinical triad of microangiopathic non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. There are infections, genetic causes, malignancies, autoimmune diseases, drugs, and many unexplained causes in the etiology of HUS. The most common cause of HUS in children is Shiga toxin-producing Escherichia coli (STEC). In the literature, few influenza A (H1N1) pdm09 virus-related HUS cases are reported. In this case report, a case with hemolytic uremic syndrome associated with influenza A (H1N1) pdm09 virus infection is presented.

Hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli infection in Argentina: update of serotypes and genotypes and their relationship with severity of the disease.

Shiga toxin-producing Escherichia coli (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS). Only few studies correlated serotypes and stx genotypes with disease severity. This study aimed to update STEC serotypes, stx genotypes, and virulence factors (eae and ehxA) in a cohort of patients with STEC-HUS and investigate whether they influence the severity of disease. In this multicentric study, children hospitalized between 2005 and 2016 with STEC-HUS confirmed by the National Reference Laboratory were included. Serotypes (O157, O145, O121, and others), stx genotypes (stx1a, stx2a, stx2c, stx2d, and others), and virulence factors were analyzed, and their association with dialysis requirement (>10 days); severe neurological, cardiovascular, and/or bowel involvement; and death was assessed. The records of 280 patients were reviewed; 160 females, median age 21 months (IQR18m). STEC O157 was isolated in 206 (73.6%) patients, O145 in 47 (16.8%), O121 in 15 (5.4%), and other serotypes in 12 (4.2%). The stx2a/2c genotype was carried by 179 (63.9%) strains, stx2a by 94 (33.6%), stx1a/stx2a by five (1.8%), and stx1a only by two (0.7%). All strains except six harbored eae and ehxA genes. Fifty-nine (21.1%) patients had severe neurological involvement, 29 (10.4%) severe bowel injury, 14 (5%) cardiovascular involvement, 53 (18.9%) required > 10 days of dialysis, and 12 (4.3%) died. Neither serotypes nor stx genotypes detected were significantly linked to severity. Serotype O157 and virulence stx2a/2c, eae, ehxA genotype are prevalent in Argentina, and no relationship was found between severity and serotypes and genotypes of STEC detected.

Genomic Characterization of hlyF-positive Shiga Toxin-Producing Escherichia coli, Italy and the Netherlands, 2000-2019.

Shiga toxin–producing Escherichia coli (STEC) O80:H2 has emerged in Europe as a cause of hemolytic uremic syndrome associated with bacteremia. STEC O80:H2 harbors the mosaic plasmid pR444_A, which combines several virulence genes, including hlyF and antimicrobial resistance genes. pR444_A is found in some extraintestinal pathogenic E. coli (ExPEC) strains. We identified and characterized 53 STEC strains with ExPEC-associated virulence genes isolated in Italy and the Netherlands during 2000–2019. The isolates belong to 2 major populations: 1 belongs to sequence type 301 and harbors diverse stx2 subtypes, the intimin variant eae-ξ, and pO157-like and pR444_A plasmids; 1 consists of strains belonging to various sequence types, some of which lack the pO157 plasmid, the locus of enterocyte effacement, and the antimicrobial resistance–encoding region. Our results showed that STEC strains harboring ExPEC-associated virulence genes can include multiple serotypes and that the pR444_A plasmid can be acquired and mobilized by STEC strains.

Acute Kidney Injury with Hemolytic Uremic Syndrome

We report here, case series of patients with acute kidney injury (AKI) developing in associationwith hemolytic uremic syndrome (HUS). Different causes of HUS and outcome of patients in this group of patients is aimed to be reported.
 Patients and Methods: subjects for the study reported here comprised of a cohort of 105 patients admitted with the diagnosis of AKI due to HUS. AKI was defined according to RIFLE criteria and HUS on basis of hematological, biochemical and/or histological features. All patients had normal size kidneys on ultrasonography and no previous co- morbidity.
 Results: One hundred and five patients with AKI due to HUS were brought to this institute from January 2000 - July 2019; among these 76 were females, mean age of these patients was 27.83±10.50 years. Causes of HUS were febrile illness, with or without diarrhea, diarrhea alone, pregnancy related complications and one each from snake bite, HCV infection / IFN therapy and use of combination of drugs. In pregnancy related HUS one patient had HUS during pregnancy while rest were during postpartum. Renal replacement was required in 95.23 % patients. Complete renal recovery was observed in 22 patients, while 15 died during acute phase of illness. CKD-V developed in 24 patients, 41 patients lost long term follow up, but were dialysis free till last follow up. Treatment with plasmapheresis revealed significantly better renal recovery (p value 0.026) in this group of patients.
 Conclusion:
 HUS can be severe life threatening disease; AKI with background of HUS may remain irreversible in many of these patients. Plasmapheresis should be offered to patients with established diagnosis of HUS.

2289 Clostridioides difficile-Associated Hemolytic Uremic Syndrome After Orthotopic Liver Transplantation

INTRODUCTION: Clostridium Difficile infection (CDI) has previously been reported as a rare cause of possible Hemolytic Uremic Syndrome (HUS) in both adults and children. We present a unique case of CDI related HUS in a patient post orthotopic liver transplantation (OLT). CASE DESCRIPTION/METHODS: A 40-year-old African American male presented with acute decompensation of alcoholic cirrhosis. After evaluation, the patient underwent successful OLT. Post-transplant course was complicated by post-operative bleeding requiring multiple exploratory laparotomies. Patient developed new-onset acute renal failure post transplantation requiring hemodialysis and prolonged courses of antibiotics. On post op day 15, patient developed diarrhea and tested positive for CDI. Physical examination was significant for jaundice, multiple ecchymoses, and a large abdominal wound without signs of excessive erythema. Laboratory data at that time showed hemoglobin drop to 5 g/dL from 8.7 g/dL, thrombocytopenia with a drop in platelets from 282 × 103/uL to 15 × 103/uL, and blood smear consistent with presence of schistocytes raising the concern for a hemolytic process. Lactate dehydrogenase (LDH) was greater than 6450 U/L, haptoglobin was less than 6 mg/dL, and reticulocytes were elevated at 8.06%. ADAMSTS-13 resulted at 26% with a negative ADMASTS-13 antibody screen suggestive against thrombotic thrombocytopenic purpura. Serotonin release assay antibodies and heparin induced thrombocytopenia antibodies were not present. A diagnosis HUS secondary to CDI was made, and the patient was started on treatment for severe CDI with oral vancomycin, vancomycin enemas, and intravenous metronidazole. The patient also underwent emergent plasma exchange receiving 4 treatments, blood transfusions, and prednisone therapy (1 mg/kg). The patient had improvement in his hemoglobin and platelets following therapy and eventual resolution of diarrhea. His mental status as well returned to baseline. Patient’s hospital course was later complicated by aright hemicolectomy, end ileostomy secondary to toxic megacolon, and pathology was consistent with pseudomembranous colitis.His renal function did not recover and he was declared end-stage renal disease. DISCUSSION: CDI related HUS is exceedingly rare. The pathogenesis of CDI related HUS has not been well defined. To our knowledge, this is the first case of CDI related HUS in a patient post OLT. It is important for gastroenterologists and hepatologists to be aware that although rare, CDI is a possible cause of HUS.

Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors

Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). The frequency of complement gene rare variants was similar in patients with secondary HUS (5%) and in healthy individuals (6% and 8% in French and European controls, respectively). At diagnosis, 40% of patients required dialysis and 18% had neurological manifestations. Fifty percent of patients received plasmatherapy and 35% were treated with eculizumab. Haematological and complete renal remission was achieved in 80% and 24% of patients, respectively. Thirty-nine percent of patients progressed to chronic kidney disease (stages 3-4) and an additional 37% reached end-stage renal disease. Eleven percent of patients died, most often from complications of the underlying cause of HUS. Only one patient experienced an HUS relapse. Patients treated with eculizumab presented with more severe HUS and were more likely to require dialysis at the time of diagnosis as compared to patients not treated with eculizumab. Rates of hematological remission, chronic kidney disease (stages 3-4), and end-stage renal disease were similar in the two groups. Secondary HUS is an acute nonrelapsing form of HUS, not related to complement dysregulation. The efficacy of eculizumab in this setting is not yet established.

678. Outbreak of Shiga Toxin-Producing Escherichia coli Infections at Marine Corps Recruit Depot (MCRD), San Diego and Camp Pendleton, California: October–November, 2017

BackgroundShiga toxin-producing Escherichia coli (STEC) infections are a major cause of foodborne illness and the principal cause of hemolytic-uremic syndrome (HUS). In November 2017, CDC and the US Navy responded to an outbreak of STEC illnesses in military recruits at the Marine Corps Recruit Depot in San Diego (MCRD). We investigated to determine the source of this outbreak and identify prevention and mitigation measures.MethodsIn October 2017, medical staff identified a high number of gastrointestinal (GI) illnesses at MCRD. Recruits with diarrhea submitted stool specimens for culture and/or culture-independent diagnostic testing (CIDT) for GI pathogens. We performed pulsed-field gel electrophoresis (PFGE) on culture isolates. Case-patients were defined as confirmed (PFGE-confirmed STEC infection matching outbreak strains), probable (diagnosis of HUS and/or CIDT evidence of STEC), or suspected (bloody diarrhea). We conducted environmental evaluations of dining facilities, training areas, and barracks. A case–control study was performed using PFGE-confirmed case-patients and platoon-matched controls. We performed product traceback for foods identified as exposure risks by interview or case–control study.ResultsWe identified 64 confirmed, 105 probable, and 91 suspected case-patients. Thirty case-patients required hospitalization and 15 had HUS. Ages ranged from 17 to 28 years (median: 18 years). Poor hygiene practices among recruits and inconsistent cooking temperatures within dining facilities were noted. Forty-three case-patients and 135 controls were interviewed about food, hygiene, and environmental exposures. Consumption of undercooked beef was significantly associated with illness (mOR 2.40, CI 1.04–5.72, P = 0.04). We identified a single ground beef supplier for MCRD, but dining facility records did not document the dates on which specific lots of ground beef were used.ConclusionCase–control analysis and environmental observations suggested undercooked ground beef as a potential source for this outbreak. We recommended the Navy and Marine Corps retain lot information, address food handling concerns, and improve hygiene among recruits.Disclosures All authors: No reported disclosures.

Hemolytic-uremic syndrome after Escherichia coli urinary tract infection in humans: systematic review of the literature.

Intestinal infections caused by a shigatoxin-positive Escherichia coli (mostly of the serogroups O26, O45, O103, O111, O121, O145 and especially O157) are a common cause of hemolytic-uremic syndrome. Hemolytic-uremic syndrome was first linked with an E. coli urinary tract infection 40years ago. We conducted a systematic review of the literature addressing the association between E. coli urinary tract infection and hemolytic-uremic syndrome. For the final analysis, we retained 23 original reports published since 1979. Five unselected pediatric case series addressed the possible occurrence of hemolytic-uremic syndrome after an acute symptomatic E. coli urinary tract infection among 266 cases and found the mentioned association in 8 (3.0%) cases. We also found 28 individual cases (17 females and 11 males) of hemolytic-uremic syndrome preceded by an E. coli urinary tract infection: 16 children aged from 2days to 6.0years and 12 adults aged from 22 to 75years. Testing for shigatoxin, performed in 19 cases, was positive in 15 cases. E. coli serotyping was performed in 18 cases: testing for serotype O157, O103 and O145 was positive in one, one and two cases, respectively, while testing for serotype O26, O45, O111 and O121 was always negative. Hemolytic-uremic syndrome rarely occurs after an acute E. coli urinary tract infection. It affects both children and adults and is mostly caused by germs that are shigatoxin-positive.

Importance of case age in the purported association between phylogenetics and hemolytic uremic syndrome in Escherichia coli O157:H7 infections.

Escherichia coli O157:H7 is the largest cause of hemolytic uremic syndrome (HUS). Previous studies proposed that HUS risk varies across the E. coli O157:H7 phylogenetic tree (hypervirulent clade 8), but the role of age in the association is unknown. We determined phylogenetic lineage of E. coli O157:H7 isolates from 1160 culture-confirmed E. coli O157:H7 cases reported in Washington State, 2004-2015. Using generalised estimating equations, we tested the association between phylogenetic lineage and HUS. Age was evaluated as an effect modifier. Among 1082 E. coli O157:H7 cases with both phylogenetic lineage and HUS status (HUS n = 76), stratified analysis suggested effect modification by age. Lineages IIa and IIb, relative to Ib, did not appear associated with HUS in children 0-9-years-old. For cases 10-59-years-old, lineages IIa and IIb appeared to confer increased risk of HUS, relative to lineage Ib. The association reversed in ⩾60-year-olds. Results were similar for clade 8. Phylogenetic lineage appears to be associated with HUS risk only among those ⩾10-years-old. Among children <10, the age group most frequently affected, lineage does not explain progression to HUS. However, lineage frequency varied across age groups, suggesting differences in exposure and/or early disease manifestation.

Pneumococcal haemolytic uraemic syndrome in the postvaccine era

ObjectivePneumococcal infection is a leading cause of haemolytic uraemic syndrome (HUS) and is potentially vaccine preventable. Published data suggest high mortality and poor renal outcomes. The introduction of the 7-valent...

Hemolytic uremic syndrome with dual caution in an infant: cobalamin C defect and complement dysregulation successfully treated with eculizumab.

Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant mortality and high risk of progression to end-stage kidney disease. It is mostly caused by dysregulation of the alternative complement pathway. Cobalamin C (Cbl C) defect is a genetic disorder of cobalamin metabolism and is a rare cause of HUS. We present a 6-month-old male infant who was admitted to the pediatric intensive care unit (PICU) due to restlessness, severe hypertension, anemia, respiratory distress, and acute kidney injury. Metabolic screening revealed elevated plasma homocysteine levels, low methionine levels, and methylmalonic aciduria, and the patient was diagnosed as having HUS secondary to Cbl C defect. Additionally, complement factor H (CFH) and complement C3 levels were decreased. The infant was treated with betaine, hydroxycobalamin, and folic acid. After treatment, the homocysteine and methylmalonic acid levels were normalized but hemolysis and acute kidney failure persisted. He required continued renal replacement treatment (CRRT) and plasma exchange due to thrombotic microangiopathy (TMA). Therefore, we considered a second mechanism in the pathogenesis as complement dysregulation and gave eculizumab to the patient. After eculizumab treatment, the renal and hematologic indices improved and he was free of dialysis. To the best of our knowledge, our patient is the first to have Cbl C defect-HUS accompanied by complement dysregulation, who responded well to eculizumab therapy.

Outcome and clinical course of EHEC O104 infection in hospitalized patients: A prospective single center study.

ObjectivesShiga-toxin producing O157:H7 Entero Haemorrhagic E. coli [STEC/EHEC] are the most common cause of Haemolytic Uraemic Syndrome [HUS] related to infectious haemorrhagic colitis. Nearly all recommendations on long term treatment of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first of this dimension to be caused by the serotype O104:H4. We report on the 3.5 year follow up of 61 patients diagnosed with symptomatic EHEC O104:H4 infection in spring 2011.MethodsPatients with EHEC O104 infection were followed in a monocentric, prospective observational study at four time points: 4, 12, 24 and 36 months. These data include the patients’ histories, clinical findings, and complications.ResultsSixty-one patients suffering from EHEC O104:H4 associated enterocolitis participated in the study at the time of hospital discharge. The mean age of patients was 43 ± 2 years, 37 females and 24 males. 48 patients participated in follow up 1 [FU 1], 34 patients in follow up 2 [FU 2], 23 patients in follow up 3 [FU 3] and 18 patients in follow up 4 [FU 4]. Out of 61 patients discharged from the hospital and included in the study, 54 [84%] were examined at least at one additional follow up. Serum creatinine decreased significantly between discharge and FU 1 from 1.3 ± 0.1 mg/dl to 0.7 ± 0.1 mg/dl [p = 0.0045]. From FU 1 until FU 4, no further change in creatinine levels could be observed. The patients need of antihypertensive medications decreased significantly [p = 0.0005] between discharge and FU 1 after four months. From FU 1 until FU 3, 24 months later, no further significant change in antihypertensive treatment was observed.ConclusionsOur findings suggest that patients free of pathological findings at time of discharge do not need a specific follow up. Patients with persistent health problems at hospital discharge should be clinically monitored over four months to evaluate chronic organ damage. Progressive or new emerging renal damage could not be observed over time in any patient.

Hemolytic Uremic Syndrome: Single Centre Experience

Introduction: Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by non-immune microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. In this study, we aimed to evaluate patients diagnosed with HUS in our clinic. Method: Patients who were diagnosed with HUS as clinic and laboratory between August 2012 and October 2017 were included in our nephrology clinic. Biochemistry, haemogram, ANA, anti-Ds DNA, p-ANCA, c-ANCA, anti-GBM antibody, C3, C4 of patients were studied. In some cases, ADAMTS13 was studied and renal biopsy was performed. The demographic features, clinics, and treatments of our cases were reviewed. Results: A total of 18 patients were enrolled in the study, the average age of the patients was 48.3 (21-82) and 10 of the cases were female and 8 of the cases were male. Among the etiologic causes of HUS in patients; the complement factor B mutation, complement factor H polymorphism, breast cancer, herbal medicine, infections and idiopathic were detected. Primer glomerulonephritis was detected in 6 cases of renal biopsy. Conclusion: Clinical and laboratory remission was obtained in 13 patients. End-stage renal failure developed in 3 of our patients.

Efficacy of eculizumab in an adult patient with HIV-associated hemolytic uremic syndrome: A case report.

Introduction:Hemolytic uremic syndrome (HUS) in Human Immunodeficiency Virus (HIV)-positive patients has become a rare cause of kidney injury since the era of highly active antiretroviral therapy (HAART). Plasma exchange and antiretroviral therapy were previously recommended but often failed to achieve remission. We report a case of HUS in a HIV-positive patient treated successfully with eculizumab.Case summary:A 52-year-old woman presented to hospital with acute renal failure, thrombocytopenia, anemia, and hypoxemia. She had been diagnosed with HIV infection in 1997. Kidney biopsy showed several fibrinous microthrombi in the glomerular capillaries, formation of thrombi in arterioles, moderate parietal and mesangial deposits of C3 and Immunoglobulin M, and intense glomerular and arterial deposits of Complement component 5b9 complement component. Serum HIV viral load was 227,848 copies/mL, and CD4 lymphocyte count was 120 cells/μL. A diagnosis of HIV-associated HUS was made. The patient had no confounding cause of HUS. Initiation of eculizumab and HAART resulted in complete hematological remission on day 32 and dialysis withdrawal on day 110. The patient has not relapsed during long-term follow-up (M17).Conclusion:This observation suggests that eculizumab can achieve remission in HIV patients with HUS.