Management of pediatric hemolytic uremic syndrome.

Classical clinical triad of hemolytic uremic syndrome (HUS) is microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury associated with endothelial cell injury. Several situations, including infections, medications, malignancies, and transplantation can trigger endothelial damage. On the HUS spectrum, atypical hemolytic uremic syndrome (aHUS) deserves special attention in pediatric patients, as it can cause endstage kidney disease and mortality. A dysfunction in the alternative complement pathway, either acquired or genetic, has been shown to be the main underlying cause. In the last decades, breathtaking advances have been made in understanding the pathophysiology of this rare disease, which has led to more efficient treatment. Recent studies have implicated genes in pathways beyond the alternative complement system, such as DGKE, TSEN2, and INF2 highlighting the importance of personalized management. Eculizumab has brought about dramatic improvements in the treatment of aHUS. Beyond eculizumab, there are many alternative therapeutics in the pipeline that target the complement system. Because of the rarity of aHUS, data from multiple patient registries are very important. The present report aimed to summarize the most important aspects of diagnosing and treating aHUS based on the Turkish national registry and the literature so as to improve clinical practice.

A case-based narrative review of pregnancy-associated atypical hemolytic uremic syndrome/complement-mediated thrombotic microangiopathy.

Atypical hemolytic uremic syndrome is a complement-mediated thrombotic microangiopathy caused by uncontrolled activation of the alternative complement pathway in the setting of autoantibodies to or rare pathogenic genetic variants in complement proteins. Pregnancy may serve as a trigger and unmask atypical hemolytic uremic syndrome/complement-mediated thrombotic microangiopathy (aHUS/CM-TMA), which has severe, life-threatening consequences. It can be difficult to diagnose aHUS/CM-TMA in pregnancy due to overlapping clinical features with other thrombotic microangiopathy syndromes including hypertensive disorders of pregnancy. However, the distinction among thrombotic microangiopathy etiologies in pregnancy is important because each syndrome has specific disease management and treatment. In this narrative review, we discuss 2 cases to illustrate the diagnostic challenges and evolving approach in the management of pregnancy-associated aHUS/CM-TMA. The first case involves a 30-year-old woman presenting in the first trimester who was diagnosed with aHUS/CM-TMA and treated with eculizumab from 19 weeks' gestation. Genetic testing revealed a likely pathogenic variant in CFI. She successfully delivered a healthy infant at 30 weeks' gestation. In the second case, a 22-year-old woman developed severe postpartum HELLP syndrome, requiring hemodialysis. Her condition improved with supportive management, yet investigations assessing for aHUS/CM-TMA remained abnormal 6 months postpartum consistent with persistent complement activation but negative genetic testing. Through detailed case discussion describing tests assessing for placental health, fetal anatomy, complement activation, autoantibodies to complement regulatory proteins, and genetic testing for aHUS/CM-TMA, we describe how these results aided in the clinical diagnosis of pregnancy-associated aHUS/CM-TMA and assisted in guiding patient management, including the use of anticomplement therapy.

Constipation and hemolytic uremic syndrome.

BACKGROUND: 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. CASE-DIAGNOSIS/TREATMENT: 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. CONCLUSION: 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.

[Various phenotypes of postpartum atypical hemolytic uremic syndrome: the role of genetic testing in determining prognosis. Case report].

We report a case of atypical hemolytic uremic syndrome (aHUS) that occurred after childbirth in a patient with a history of numerous recurrent episodes of TMA with nephrotic proteinuria and impaired renal function. At 33 weeks of the first spontaneous pregnancy, proteinuria up to 0.8 g/l was first registered, at 38 weeks she was hospitalized with proteinuria, reaching a maximum of 13 g/l, she was delivered promptly, after which progressive thrombocytopenia was noted over the next few days (up to 44×109/l) and anemia and severe arterial hypertension, which could not be corrected by several groups of antihypertensive drugs. Initiated plasma therapy had no effect. After exclusion of all other causes of TMA, therapy with eculizumab was initiated, which made it possible to quickly and completely stop the phenomena of TMA. The presented observation demonstrates the successful treatment of recurrent course of aHUS with eculizumab with the achievement of complete recovery of kidney function in a patient with a homozygous mutation in the MCP gene. It is worth noting the importance of genetic research even in those situations where clinically aHUS is beyond doubt.

Atypical hemolytic and uremic syndrome in Algeria: diagnostic difficulties and therapeutic constraints / Syndrome hémolytique et urémique atypique en Algérie : difficultés diagnostiques et contraintes thérapeutiques

Atypical Hemolytic Uremic Syndrome (aHUS) is a systemic disease due to dysregulation of the alternate complement pathway, mortality is estimated at 10% and more than 50% of patients progress to end-stage renal disease. The aim of this study was to summarize the clinical data and biological results as well as the evolution and management of patients with aHUS seen over a period of four years in one specialized department in Algeria. Our study was observational and longitudinal. The inclusion criteria were: the clinical-biological triad of aHUS and age ≤ 16 years. The type of treatment, the presence of complement mutation or anti-complement factor autoantibodies were not eligibility conditions. On inclusion and every six months, demographic data, clinical and biological history and results after treatment were collected prospectively. Our workforce consisted of 21 children with aHUS. Thirteen patients benefited from a complement study; among them, 7 had complement abnormalities. Eleven children had familial HUS; among them 8 died and 6 were less than one year old. Plasma exchanges were performed in two children. Six patients received eculizumab, with an average age of 3.6 years. After the acute phase, 9 children recovered their kidney function, one child had developed a chronic kidney disease (CKD), and 11 died, among them 8 belong to aHUS families. Fifty percent of deaths occurred in the first 3 months. At 2 years of evolution, out of 7 children having reached this stage, five had renal sequelae and four of them had CKD. The severe prognosis of this disease makes early diagnosis and treatment essential.

Le syndrome hémolytique et urémique atypique (SHUa) est une maladie systémique due à une dérégulation de la voie alterne du complément. La mortalité est estimée à 10 % et plus de 50 % des patients évoluent vers l'insuffisance rénale terminale. Le but de la présente étude était de résumer les données cliniques et les résultats biologiques ainsi que l'évolution et la prise en charge des patients atteints de SHUa vus sur une durée de quatre ans dans un service spécialisé en Algérie. Notre étude était observationnelle et longitudinale. Les critères d'inclusion étaient : la triade clinico-biologique du SHUa et l'âge ≤ 16 ans. Le type de traitement, la présence de mutation du complément ou d'auto-anticorps anti-facteur du complément ne constituaient pas des conditions d'éligibilité. À l'inclusion et tous les six mois, les données démographiques, l'histoire clinique, biologique et les résultats après traitement étaient collectés prospectivement. Notre effectif était formé de 21 enfants avec SHUa. Treize patients ont bénéficié d'une étude du complément ; parmi eux sept avaient des anomalies du complément. Onze enfants avaient un SHU familial ; parmi eux huit sont décédés et six avaient moins d'un an. Des échanges plasmatiques ont été réalisés chez deux enfants. Six patients ont bénéficié d'éculizumab, avec un âge moyen de 3,6 ans. Après la phase aiguë, neuf enfants avaient récupéré leur fonction rénale, un enfant avait gardé une insuffisance rénale chronique (IRC), et 11 enfants étaient décédés dont huit appartenaient à des familles de SHUa. Cinquante pourcent des décès étaient survenus durant les trois premiers mois. À deux ans d'évolution, sur sept enfants ayant atteint ce stade, cinq avaient des séquelles rénales et quatre d'entre eux étaient en IRC. Le pronostic sévère de cette maladie rend la précocité du diagnostic et de la prise en charge primordiales.

Atypical haemolytic uraemic syndrome in a postpartum patient.

A postpartum patient presented 1 week following uncomplicated pregnancy and elective repeat caesarean section with acute hypertension, severe anaemia and acute kidney injury. Her workup demonstrated microangiopathic anaemia, thrombocytopenia and liver enzyme elevations. Differential diagnoses included postpartum haemolysis-elevated liver enzyme-low platelet (HELLP) syndrome, haemolytic uraemic syndrome (HUS), and thrombotic thrombocytopenic purpura (TTP). She was treated initially with systemic corticosteroids, haemodialysis and plasmapheresis for presumed TTP while awaiting the results of ADAMSTS13 assay performed at an outside laboratory. When reported back as normal, the diagnosis of atypical HUS was established. Eculizumab was administered with rapid improvement of her condition.

Why has plasma exchange failed in TRACK syndrome? Lessons from a new variant of the atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening form of thrombotic microangiopathy, associated with high mortality and morbidity. Most cases present with hemolytic anemia, thrombocytopenia, and renal insufficiency. However, it can have unusual multiple end-organ injuries including extrarenal organ and system involvements such as neurologic, cardiac, gastrointestinal, and respiratory systems. We describe a 4-year-old girl who developed aHUS due to the TSEN2 mutation and had cardiac involvement. She did not benefit from plasma exchange, as stated in previous cases. It should be kept in mind that therapeutic plasma exchange may not be beneficial in some cases of aHUS, especially due to genetic mutations.

The nailfold dermoscopy findings of patients with atypical haemolytic uremic syndrome.

INTRODUCTION: Hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic anemia, thrombocytopenia, and acute renal failure. OBJECTIVES: Atypical HUS (aHUS) that results due to genetic disorders of the alternative complement pathway results in inflammation, endothelial damage, and kidney injury. Therefore, simple and non-invasive tests are needed to evaluate the activity of the disease by assessing the microvascular structure in aHUS. METHODS: A dermoscope (×10) is an inexpensive and easily portable device used to visualize nailfold capillaries and has high clinical performance and interobserver reliability. In this study, the nailfold capillaries of patients with aHUS who were in remission under eculizumab treatment were examined, and the findings were compared to those of a healthy control group to evaluate disease characteristics. RESULTS: All children with aHUS had decreased capillary densities even if they were in remission. This may be indicative of ongoing inflammation and microvascular damage in aHUS. CONCLUSION: A dermoscopy can be used as a screening tool for disease activity in patients with aHUS.

Hemolytic Uremic Syndrome: A Case Report.

Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any body organ leading to thrombocytopenia, coombs-negative hemolytic anemia, and end-organ damage. The clinical presentation of the case shows typical hemolytic uremic syndrome, however, lab reports show atypical hemolytic uremic syndrome (low C3). Pain abdomen and loose stool with some signs of dehydration were initial presentations. Early initiation of renal replacement therapy and management of dehydration was done. Simple diarrhea can also manifest as acute kidney injury with the hemolytic uremic syndrome. Hence we should keep hemolytic uremic syndrome as the differential diagnosis of diarrhea. Irrespective of lab parameters, early management in line with the typical hemolytic uremic syndrome should be done for better outcomes. Keywords: anemia; case reports; dehydration; renal replacement therapy.

Better late than never: Diagnosis of recurrent atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) comprising microangiopathic hemolytic anemia, consumptive thrombocytopenia, and end-organ damage. Risk of end-stage renal disease is increased as HUS usually manifests in native and transplanted kidneys. In transplants, while de novo disease can be seen, recurrent disease is more common. The etiology is variable, being either primary or secondary. aHUS often constitutes a diagnostic and therapeutic challenge, which may lead to a considerable delay in the diagnosis and treatment. During the last decades, great progress has been made in understanding the mechanisms and therapeutic options of this devastating condition. We present a case of a 50-year-old female who received her first kidney transplant from her mother at the age of 9 years. She experienced recurrent losses of transplants, and only after the loss of her fourth transplant did the diagnosis of aHUS become evident.

Atypical Hemolytic Uremic Syndrome in a Pregnant Patient with a Thrombomodulin Gene Variant Treated with Plasma Exchange and Eculizumab.

BACKGROUND Hemolytic uremic syndrome (HUS) includes the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The atypical form of HUS is a rare disease characterized by complement overactivation, and it can be from genetic or acquired causes. Genetic causes involve mutation in one of the factors in the alternative complement pathway or inhibitors. Malignant hypertension and pregnancy are the most important acquired causes. The optimal management of patients with aHUS is with eculizumab, which is recombinant antibody against human complement component C5. CASE REPORT This report describes the case of a 25-year-old woman with frequent hospitalizations for poorly controlled hypertension who presented at 20 weeks of gestation with headache, vomiting, and a blood pressure of 230/126 mmHg. The patient had acute kidney injury with hematuria and proteinuria, and kidney biopsy showed hypertensive arteriolar nephrosclerosis and fibrinoid arteriolar necrosis consistent with thrombotic microangiopathy. Further work-up with a genetic panel showed heterozygosity for the thrombomodulin (THBD) gene. She was started on treatment with plasma exchange and eculizumab, a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein. The patient responded well to the treatment at the time of her initial outpatient follow-up. CONCLUSIONS This case shows the potential of severe renal manifestation of aHUS, and the need for a kidney biopsy in cases of severe uncontrolled hypertension presenting with kidney injury. If evidence of aHUS is found, prompt treatment with plasma exchange and eculizumab should be initiated.

Post-traumatic stress disorder and quality of life alterations in survivors of immune-mediated thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome.

Thrombotic thrombocytopenic purpura (iTTP) and atypical hemolytic-uremic syndrome (aHUS), once in remission, may cause long-term symptoms, among which mental-health impairments may be difficult to detect. We conducted telephone interviews 72 [48-84] months after ICU discharge to assess symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) and the 36-item Short Form questionnaire (SF-36). Of 103 included patients, 52 had iTTP and 51 aHUS; 74% were female, median age was 39 y (31-54), and 39 (38%) patients were still taking treatment. Symptoms of anxiety, PTSD and depression were present in 50%, 27% and 14% of patients, respectively, with no significant difference between the iTTP and aHUS groups. Patients with PTSD symptoms had significantly greater weight gain and significantly worse perceived physical and/or emotional wellbeing, anxiety symptoms, and depression symptoms. The SF-36 physical and mental components indicated significantly greater quality-of-life impairments in patients with vs. without PTSD symptoms and in those with aHUS and PTSD vs. iTTP with or without PTSD. In the aHUS group, quality of life was significantly better in patients with vs. without eculizumab treatment. Factors independently associated with PTSD symptoms were male sex (odds ratio [OR], 0.11; 95%CI, 0.02-0.53), platelet count ≤20 G/L at acute-episode presentation (OR, 2.68; 1.01-7.38), and current treatment (OR, 2.69; 95%CI, 1.01-7.36). Mental-health screening should be routine in patients with iTTP and aHUS to ensure appropriate care.

A case report of an atypical haemolytic uremic syndrome in pregnancy: something wicked this way comes.

BACKGROUND: Atypical Haemolytic Uremic Syndrome is an acute life-threatening condition, characterized by the clinical triad of microangiopathic hemolytic anaemia, thrombocytopenia, kidney injury. Management of pregnants affected by Atypical Haemolytic Uremic Syndrome can be a serious concern for obstetric anesthesiologist in the delivery room and in the intensive care unit. CASE PRESENTATION: A 35-year-old primigravida with a monochorionic diamniotic twin pregnancy, presented with an acute haemorrhage due to retained placenta after elective caesarean section and underwent surgical exploration. In the postoperative period, the patient progressively developed hypoxemic respiratory failure and, later on, anaemia, severe thrombocytopenia, and acute kidney injury. A timely diagnosis of Atypical Haemolytic Uremic Syndrome was made. Non-invasive ventilation and high-flow nasal cannula oxygen therapy sessions were initially required. Hypertensive crisis and fluid overload were aggressively treated with a combination of beta and alpha adrenergic blockers (labetalol 0,3 mg/kg/h by continuous intravenous infusion for the first 24 hours, bisoprolol 2,5 mg twice daily for the first 48 hours, doxazosin 2 mg twice daily), central sympatholytics (methyldopa 250 mg twice daily for the first 72 hours, transdermal clonidine 5 mg by the third day), diuretics (furosemide 20 mg three times daily), calcium antagonists (amlodipine 5 mg twice daily). Eculizumab 900 mg was administered via intravenous infusion once per week, attaining hematological and renal remissions. The patient also received several blood transfusion units and anti- meningococcal B, anti-pneumococcal, anti-haemophilus influenzae type B vaccination. Her clinical condition progressively improved, and she was finally discharged from intensive care unit 5 days after admission. CONCLUSIONS: The clinical course of this report underlines how crucial it is for the obstetric anaesthesiologist to promptly identify Atypical Haemolytic Uremic Syndrome, since early initiation of eculizumab, together with supportive therapy, has a direct effect on patient outcome.

Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain.

INTRODUCTION: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. METHODS: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. RESULTS: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5-16.5). Two children died. CONCLUSIONS: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data.

Complement-driven hemolytic uremic syndrome.

Overactivation of the complement alternative pathway drives the pathogenesis of primary atypical hemolytic uremic syndrome (aHUS). Genetically-determined or acquired dysregulation of the complement is frequently identified in patients with aHUS, pregnancy-related hemolytic uremic syndrome (HUS), and severe hypertension-associated HUS. In contrast, it is still unclear whether self-limited complement activation, which frequently occurs in other forms of HUS, provides key mechanistic clues or results from endothelial damage. Development of novel biomarkers is underway to firmly establish complement-driven pathogenesis. C5 blockade therapy has revolutionized the management of aHUS patients, resulting in a halving of the subpopulation under chronic dialysis over the course of a few years. On the other hand, the efficacy of C5 blockade in secondary forms of HUS, as assessed by small and uncontrolled case series, is less compelling and should be investigated through properly designed prospective clinical trials. The increased risk of meningococcal infection, related to C5 inhibition, must be rigorously addressed with suitable prophylaxis. Treatment duration should be determined based on an individualized benefit/risk assessment.

PURTSCHER-LIKE RETINOPATHY ASSOCIATED WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME: CASE REPORT AND REVIEW OF OUTCOMES.

PURPOSE: The purpose of this study was to report the case of a patient presenting with newly diagnosed atypical hemolytic uremic syndrome (aHUS) and Purtscher-like retinopathy. METHODS: This is an observational case report and review of literature. A 38-year-old woman presented with 3 months of rashes, fevers, arthralgias, and abdominal pain. Initial workup was suggestive of hypereosinophilic syndrome or adult-onset Still's disease. The patient developed acute renal failure and progressively blurry vision bilaterally over the course of 5 days. Funduscopic examination was notable for numerous Purtscher flecken and cotton-wool spots, with rare intraretinal hemorrhages at the posterior pole. The constellation of renal failure, hemolytic anemia, and thrombocytopenia prompted a workup for thrombotic microangiopathy that was remarkable for a mutation in the gene coding for complement protein C9. RESULTS: The patient was diagnosed with aHUS and treated with intravenous pulse dose steroids for 3 days and an extended course of eculizumab. The patient's renal failure resolved, and her visual acuity improved, although she had residual visual field constriction and developed bilateral optic atrophy. Outcomes of other cases of Purtscher-like retinopathy related to aHUS are reviewed. CONCLUSION: Purtscher-like retinopathy is a rare but severe ophthalmic complication of aHUS. Eculizumab is an effective treatment for the systemic illness caused by aHUS, and anatomical resolution of Purtscher-like retinopathy may follow, although visual prognosis remains guarded. Recovery of visual acuity may lag behind resolution of macular edema in these patients.

The complement system in pediatric acute kidney injury.

The complement cascade is an important part of the innate immune system. In addition to helping the body to eliminate pathogens, however, complement activation also contributes to the pathogenesis of a wide range of kidney diseases. Recent work has revealed that uncontrolled complement activation is the key driver of several rare kidney diseases in children, including atypical hemolytic uremic syndrome and C3 glomerulopathy. In addition, a growing body of literature has implicated complement in the pathogenesis of more common kidney diseases, including acute kidney injury (AKI). Complement-targeted therapeutics are in use for a variety of diseases, and an increasing number of therapeutic agents are under development. With the implication of complement in the pathogenesis of AKI, complement-targeted therapeutics could be trialed to prevent or treat this condition. In this review, we discuss the evidence that the complement system is activated in pediatric patients with AKI, and we review the role of complement proteins as biomarkers and therapeutic targets in patients with AKI.

How I diagnose and treat atypical hemolytic uremic syndrome.

Our understanding and management of atypical hemolytic uremic syndrome (aHUS) have dramatically improved in the last decade. aHUS has been established as a prototypic disease resulting from a dysregulation of the complement alternative C3 convertase. Subsequently, prospective nonrandomized studies and retrospective series have shown the efficacy of C5 blockade in the treatment of this devastating disease. C5 blockade has become the cornerstone of the treatment of aHUS. This therapeutic breakthrough has been dulled by persistent difficulties in the positive diagnosis of aHUS, and the latter remains, to date, a diagnosis by exclusion. Furthermore, the precise spectrum of complement-mediated renal thrombotic microangiopathy is still a matter of debate. Nevertheless, long-term management of aHUS is increasingly individualized and lifelong C5 blockade is no longer a paradigm that applies to all patients with this disease. The potential benefit of complement blockade in other forms of HUS, notably secondary HUS, remains uncertain.

Atypical hemolytic uremic syndrome: Consensus of diagnosis and treatment in Taiwan.

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.