Dilated Cardiomyopathy during the Course of Hemolytic Uremic Syndrome

A 47-year-old woman presented with severe hemolytic uremic syndrome (HUS) followed by heart failure. An echocardiogram showed an ejection fraction of 20%, and a cardiac catheterization followed by a myocardial histologic evaluation demonstrated dilated cardiomyopathy. Plasma exchange and hemodialysis were performed regularly. The later outcomes of renal function and cardiomyopathy were favorable. A review of the literature confirmed the rare and severe nature of cardiac lesions occurring in the course of HUS. This case indicates the importance of cardiac monitoring in HUS and the need for prolonged support.     

Diagnosis and Management of Atypical Hemolytic Uremic Syndrome In Children: Single Centre Experience

Atypical hemolytic uremic syndrome (aHUS) although rare is the commonest cause of acute renal failure (ARF) in children and has poor prognosis. We present single centre experience of aHUS. Thirty six children (29 males, 7 females) with mean age, 7.9 years presented with ARF, 2 children also had tonic–clonic type convulsions. Their hematology examination revealed hemolytic anemia with s. creatinine (SCr), 5.54 mg/dl. Acute HUS was observed in 75 %, acute on chronic HUS in 19.4 % and patchy cortical necrosis (PCN) in 5.6 % biopsies. Mean 5.4 plasma exchanges (PE) were carried out. Supportive management of anti-hypertensives and prednisone was also given. Recovery end points were establishment of urine output, improvement of SCr and hematological profile. Hematology and renal function profile improved variably in all children, 5.6 % died, relapse was observed in 80.5 % over mean 70 days; 13.9 % children are doing well over mean follow-up of 268.8 days. Thus poor prognosis was observed in 86.1 % children. Children with acute on chronic HUS and PCN did not recover. Six children who recovered had acute HUS. aHUS in Indian children occurs at an older age of around 8 years and chronic/irreversible changes on histopathology examination are harbingers of poor prognosis. PE is life-saving however further research for developing strategies to improve long-term survival is needed.     

Clinical Outcome in Three Patients with Postpartum Hemolytic Uremic Syndrome Treated with Frequent Plasma Exchange

Abstract: This study reviewed 3 cases of postpartum hemolytic uremic syndrome (HUS) at our hospital over a 3 year period. The 3 patients had clinical and laboratory abnormalities similar to those of 12 patients with other causes of thrombotic microangiopathy presenting during the same time span. Both groups were treated with 4–7 plasma exchange treatments/week and prednisone, 60 mg/ day or its intravenous equivalent, until remission. The postpartum HUS patients had a more complicated, prolonged course; 3 of 3 required dialysis compared to 4 of 12 in the nonpostpartum group (p > 0.05), and they required more plasma exchange treatments (49 ± 17 vs. 10 ± 8, p = 0.0001) and a longer duration of therapy (70 ± 31 vs. 19 ± 17 days, p > 0.01) before remission. All postpartum HUS patients discontinued dialysis and survived whereas 4/12 nonpostpartum patients died before attaining remission. Compared to other variants of thrombotic microangiopathy, postpartum HUS requires a longer duration of therapy, but with aggressive therapy, renal and overall prognoses may be better.     

Atypical Hemolytic Uremic Syndrome: Beyond Hemolysis and Uremia

Atypical hemolytic uremic syndrome commonly presents with the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal function impairment without an antecedent hemorrhagic diarrhea. Less known are extrarenal complications due to abnormal vascular permeability, although these are a major cause of morbidity and mortality for the patients. Furthermore, it is increasingly recognized that the disease may present with hypertension or renal function impairment with no or mild thrombocytopenia and microangiopathic hemolytic anemia. Awareness of the full spectrum of atypical hemolytic uremic syndrome may facilitate its diagnosis and treatment before serious complications or death occurs.     

Extracorporeal Plasma Treatment in Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome: A Review

Abstract: This review summarizes the state of the art of apheresis in hemolytic uremic syndrome (HUS) and in thrombotic thrombocytopenic purpura (TTP). Both entities are characterized by thrombotic microangiopathy, hemolytic anemia, and thrombocytopenia. While HUS often presents with renal insufficiency, cerebral involvement is more common in TTP. Recently, in TTP, a primary or secondary lack of activity of a von Willebrand factor (vWF) degrading enzyme was made responsible for the presence of unusually large vWF multimers causing platelet aggregation and thrombus formation in the microvasculature. In contrast, in familial HUS, a factor H deficiency with uninhibited complement activation seems to play a role. Therapeutic plasma exchange (TPE) using fresh frozen plasma or cryosupernatant as the substitution fluid is indicated in acute TTP and atypical HUS without antecedent diarrhea. As a rule, it will show good effectiveness, especially in the former entity. HUS in pregnancy should be treated by instant delivery whereas postpartum HUS may resolve using protracted courses of TPE. In contrast, in thrombotic microangiopathy after bone marrow transplantation as well as in HUS due to cancer, mitomycin C, or after renal transplantation, TPE is of questionable value and indicated only as a last resort treatment.     

Characterization of a New DGKE Intronic Mutation in Genetically Unsolved Cases of Familial Atypical Hemolytic Uremic Syndrome

Background and objectives

Genetic and acquired abnormalities causing dysregulation of the complement alternative pathway contribute to atypical hemolytic uremic syndrome (aHUS), a rare disorder characterized by thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute kidney failure. However, in a substantial proportion of patients the disease-associated alterations are still unknown.

Design, setting, participants, & measurements

Whole-exome and whole-genome sequencing were performed in two unrelated families with infantile recessive aHUS. Sequencing of cDNA from affected individuals was used to test for the presence of aberrant mRNA species. Expression of mutant diacylglycerol kinase epsilon (DGKE) protein was evaluated with western blotting.

Results

Whole-exome sequencing analysis with conventional variant filtering parameters did not reveal any obvious candidate mutation in the first family. The report of aHUS-associated mutations in DGKE, encoding DGKE, led to re-examination of the noncoding DGKE variants obtained from next-generation sequencing, allowing identification of a novel intronic DGKE mutation (c.888+40A>G) that segregated with disease. Sequencing of cDNA from affected individuals revealed aberrant forms of DGKE mRNA predicted to cause profound abnormalities in the protein catalytic site. By whole-genome sequencing, the same mutation was found in compound heterozygosity with a second nonsense DGKE mutation in all affected siblings of another unrelated family. Homozygous and compound heterozygous patients presented similar clinical features, including aHUS presentation in the first year of life, multiple relapsing episodes, and proteinuria, which are prototypical of DGKE-associated aHUS.

Conclusions

This is the first report of a mutation located beyond the exon-intron boundaries in aHUS. Intronic mutations such as these are underreported because conventional filtering parameters used to process next-generation sequencing data routinely exclude these regions from downstream analyses in both research and clinical settings. The results suggest that analysis of noncoding regions of aHUS-associated genes coupled with mRNA sequencing might provide a tool to explain genetically unsolved aHUS cases.     

Renal Damage in Recurrent Atypical Hemolytic Uremic Syndrome Associated with C3 p.Ile1157Thr Gene Mutation

Patients with atypical hemolytic uremic syndrome (aHUS) associated with a C3 p.Ile1157Thr mutation show a relatively high renal survival and low mortality rates, but renal histopathological findings after recurrence have been rarely reported. A 30-year-old man with a C3 p.Ile1157Thr mutation experienced a third recurrence of thrombotic microangiopathies with neurological and gastrointestinal disorders. A renal biopsy performed during the recovery phase of acute kidney injury revealed collapsed glomeruli and arteriolar vacuolization. Approximately 10% of glomeruli were globally sclerotic, despite the absence of arterio-/arteriolo-sclerosis. These findings suggest substantial progression of irreversible injuries in multiple organs, including kidneys, which occurs in aHUS patients with repeated thrombotic microangiopathies.     

体外循环致溶血性尿毒症综合征一例

溶血性尿毒症综合征（hemolytic uremic syndrome,HUS）是一组以微血管病性溶血性贫血、血小板减少和肾功能衰竭为主要表现的临床综合征,婴幼儿常见,早期诊断并采取有效治疗措施可降低病死率。HUS由体外循环所致者报道很少。本文报告一例体外循环心脏手术后的HUS,以及成功治疗的经验。     

Hemolytic uremic syndrome with ischemic glomerulonephropathy and obliterative vasculopathy in a systemic sclerosis patient treated with cyclosporine-A

Hemolytic uremic syndrome (HUS) is not a commonly reported complication in post-transplantation patients treated with cyclosporine-A (CSA), and is extremely rare in systemic sclerosis (SSc) patients treated with this drug. CSA may contribute to the development of chronic ischemic glomerulonephropathy and vasculopathy, features not easily distinguished from SSc-related nephropathy. Here, we describe a 41-year-old Chinese man with diffuse-type SSc treated with CSA who developed thrombocytopenia, acute renal failure and hemolytic anemia and was diagnosed with HUS. Renal function and thrombocytopenia improved gradually after intensive treatment of plasma exchange (PE) and high-dose steroid therapy. After PE, renal biopsy showed ischemic glomerulonephropathy and obliterative vasculopathy. This case illustrates that PE can improve the hematological disorders and characteristic renal changes of HUS in SSc patients treated with CSA. However, this therapy may not be effective in normalizing serum creatinine level in SSc patients once CSA has triggered the normal kidney to develop glomerulonephropathy and vasculopathy with ischemic and sclerotic changes.     

Successful Treatment of Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura with Fresh Frozen Plasma and Plasma Exchange

ABSTRACT. Four patients with hemolytic uremic syndrome (HUS) and seven with thrombotic thrombocytopenic purpura (TTP) were treated with infusions of fresh frozen plasma (FFP). In one patient with HUS and Ave patients with TTP this treatment was combined with plasma exchange (PE). The additional treatment varied; corticosteroids, antiplatelet drugs, heparin and blood exchange. All but one patient recovered completely in spite of severe illness with uremia, oliguria and/or cerebral symptoms during the acute phase. The results were surprisingly good in comparison with other published series. The success must in the first place be attributed to early diagnosis and to the infusions of FFP. PE seemed to potentiate the effect of FFP.     

Anticomplement Treatment in Atypical and Typical Hemolytic Uremic Syndrome

The dissection of the pathogenic mechanisms of the various forms of the hemolytic uremic syndrome (HUS) has paved the way for the design of specific efficacious treatments. Such mechanistic approach led to a revolution in the management of atypical HUS with the use of the first-in class C5 blocker, eculizumab. The availability of this anticomplement drug has also raised unsettled questions regarding the cost or burden and optimal duration of therapy and its use in secondary HUS. The efficacy of eculizumab in Shiga toxin producing Escherichia coli-associated HUS is not to date established and the results of ongoing prospective studies are eagerly awaited. Nevertheless, the emergence of anticomplement therapies (eculizumab and other drugs in development) has transformed our approach of HUS.     

At the Cross Section of Thrombotic Microangiopathy and Atypical Hemolytic Uremic Syndrome: A Narrative Review of Differential Diagnostics and a Problematization of Nomenclature

Complement‐mediated atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with high mortality and morbidity. Renal biopsies often indicate thrombotic microangiopathy (TMA). The condition is caused by an excessive activation of the alternative pathway leading to depositions of membrane attack complexes (MAC) on host cells. It may depend on mutations in complement components and regulatory proteins, or the formation of complement‐specific antibodies. Mainly, an environmental trigger (e.g. infection) is needed for the excessive response to develop. The clinical characteristics are more or less shared with a wide range of diseases manifesting with microangiopathic hemolytic anemia. Because of prior deficits in pathogenic understanding, associated nomenclature has been based on clinical symptoms. New knowledge challenges these symptomatic definitions; however, an outdated terminology is still being applied in clinical practice to various extents. With respect to gained insights, it is more advantageous to rebuild the concepts on etiological and pathogenic grounds. The need for more distinct definitions is even more urgent in the light of the effective treatment regimen with eculizumab for complement‐mediated aHUS. This review presents an up‐to‐date summary of the field of investigation, addresses the need for faster differential diagnostics and proposes a revised nomenclature based on the current pathogenic understanding.     

Hemolytic uremic syndrome in a patient on cis-platinum,vinblastine and bleomycin

Summary A 23-year-old woman with metastatic Sertoli-Leydig cell tumor was treated with cisplatin, vinblastine, and bleomycin. Hemolytic uremic syndrome appeared, while no evidence of residual tumor was found. Infusion of fresh frozen plasma together with aspirin and dipyridamole resulted in recovery of microangiopathic hemolytic anemia and thrombocytopenia. Renal insufficiency, however, persisted.     

Therapeutic Apheresis for Cancer Related Hemolytic Uremic Syndrome

Abstract: Hemolytic uremic syndrome (HUS) can be seen as a result of disseminated cancer, as a consequence of chemotherapy, or in association with bone marrow transplantation (BMT). Further distinction can be made when the clinical presentation is that of an acute, fulminant course with rapidly progressive renal failure or that of a sub‐acute form with a slow progression of renal involvement. Each of the different etiologies (cancer, chemotherapy, or BMT) and each of the two basic clinical presentations has its own prognosis. There are no randomized, controlled studies to elucidate the role of therapeutic apheresis for cancer‐related HUS. Hemolytic uremic syndrome related to disseminated cancer is most often a terminal event and is not commonly treated with apheresis procedures, although there are anecdotal reports that plasma exchange may be beneficial. Chemotherapy and drug‐related HUS have a prognosis that is strongly dependent on the severity of the presentation, but even in the most severe cases may respond to either immunoadsorption or plasma exchange with fresh frozen plasma (FFP). Finally, BMT‐related HUS has a poor prognosis but may respond to immunoadsorption, plasma exchange, or a combination of the two.     

Autoimmune Polyglandular Syndrome Type 3c with Ectodermal Dysplasia,Immune Deficiency and Hemolytic-Uremic Syndrome

Autoimmune polyglandular syndrome (APS) is a disorder which is associated with multiple endocrine gland insufficiency and also with non-endocrine manifestations. The pathophysiology of APS is poorly understood, but the hallmark evidence of APS is development of autoantibodies against multiple endocrine and non-endocrine organs. These autoantibodies are responsible for the dysfunction of the affected organs and sometimes may also cause non-endocrine organ dysfunction. The hemolytic-uremic syndrome (HUS) is a serious and life-threatening disease which develops due to many etiological factors including autoimmune disorders. Here, we present an unusual case of APS. Ectodermal dysplasia with immune deficiency and HUS occurred concomitantly in the same patient with APS type 3c. Once the autoantibody generation was initiated in the human body, development of multiple disorders due to organ dysfunction and also autoantibody-related diseases may have occurred.     

Campylobacter-Associated Hemolytic Uremic Syndrome Associated with Pulmonary-Renal Syndrome

Common causes of pulmonary-renal syndrome include anti-glomerular basement membrane (anti-GBM) disease anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis, and systemic lupus erythematosus. We describe a case of life-threatening pulmonary hemorrhage associated with Campylobacter hemolytic uremic syndrome (HUS), which we believe is a new disease entity. We hypothesize that the cause of this pulmonary-renal syndrome was an immunological reaction to Campylobacter; and that the initiation of high-dose steroids was responsible for the rapid reversal of the patient’s pulmonary and renal impairment. The aim of this article is to raise awareness of this unusual cause of a pulmonary-renal syndrome, guiding physicians to recognize it as a potential complication, and to consider high-dose steroids in managing the condition.KEY WORDS: Campylobacter jejuni, hemolytic uremic syndrome, pulmonary hemorrhage