Atypical Hemolytic Uremic Syndrome Can Present as Malignant Hypertension and Renal Dysfunction

2017 ◽  
Vol 69 (4) ◽  
pp. A20
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Renal Dysfunction ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Uremic Syndrome

scholarly journals Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome

2019 ◽  
Vol 96 (4) ◽  
pp. 995-1004 ◽  
Author(s):  
Teresa Cavero ◽  
Emilia Arjona ◽  
Karina Soto ◽  
Fernando Caravaca-Fontán ◽  
Cristina Rabasco ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Uremic Syndrome

scholarly journals Complement Activation and Thrombotic Microangiopathies

2019 ◽  
Vol 14 (12) ◽  
pp. 1719-1732 ◽  
Author(s):  
Marta Palomo ◽  
Miquel Blasco ◽  
Patricia Molina ◽  
Miquel Lozano ◽  
Manuel Praga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Acute Phase ◽  
Complement Activation ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Clinical Relapse ◽  
Thrombotic Microangiopathies ◽  
Uremic Syndrome

Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma—citrated plasma mixed with a control sera pool (1:1)—to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome–activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6–9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.

scholarly journals A Challenging Case of Atypical Hemolytic Uremic Syndrome in a Young African American Patient

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4225-4225
Author(s):  
Urwat Til Vusqa ◽  
Palash Asawa ◽  
Yazan Samhouri ◽  
Rama Bhagavatula ◽  
Robert B. Kaplan
Keyword(s):  
Blood Pressure ◽  
African American ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Coagulation Cascade ◽  
Complement Factors ◽  
Uremic Syndrome ◽  
Terminal Complement

Abstract Background It is known that malignant hypertension (mHTN) and thrombotic microangiopathy (TMA) commonly coexist. Deciding which phenomenon preceded the other remains a clinical dilemma, specifically in African American patients. However, making that determination is of utmost importance because the management will be different, and that can have dramatic effects on prognosis and outcomes. Herein, we report a case of atypical hemolytic uremic syndrome (aHUS) presenting as mHTN. Case Presentation A 35-year-old African American male with known history of hypertension, presented with nausea, vomiting, and diarrhea for four days. He also reported fatigue and exertional shortness of breath. Upon presentation, his blood pressure was 260/160 mmHg, otherwise physical exam was unremarkable. Initial work up showed hemoglobin of 8.8 g/dL (baseline 13.5), platelet count of 21,000/mL (baseline 250,000), serum creatinine of 16.99 mg/dL (baseline 0.99), MCV (84 fl), increased reticulocyte production index (3.58), increased LDH (1709 U/L), undetectable haptoglobin, and numerous schistocytes on peripheral blood smear. He was admitted as a case of hypertensive emergency and TMA. IV labetalol and hemodialysis were started. Given his gastrointestinal symptoms; stool for Shigella and E.Coli O157:H7 were checked and they were negative. Given the severity of his hematologic derangements and difficult to control blood pressure, we decided to proceed with renal biopsy to rule out primary aHUS which showed thrombotic microangiopathy, global glomerulosclerosis, moderate interstitial fibrosis and tubular atrophy suggestive of aHUS or rheumatologic disorders like systemic sclerosis and arguing against malignant HTN as the sole player. ANA and anti-Scl-70 antibodies were negative. Final impression was aHUS by exclusion, and patient received meningococcal vaccines (Menactra and Bexsero) in preparation to start eculizumab. aHUS genetic panel was sent which came back equivocal as it showed mutations of unknown significance (homozygous missense mutation in the MASP2 gene and 2 heterozygous mutations in the C2 gene). He was started on eculizumab 900 mg weekly for 4 weeks then 1200 mg biweekly starting week 5. He was seen in the office 2 months after initial presentation and receiving 5 doses of Eculizumab. His kidney function showed improvement with > 2 liters of urine output daily, blood pressure was better controlled. A decision by nephrology was made to give him a break from dialysis and remains dialysis-free a year later. Discussion aHUS is a rare disorder with an estimated prevalence of seven per one million children in Europe. It causes uninhibited activation of complement factors that leads to renal endothelial damage and activation of coagulation cascade leading to TMA. The diagnosis of aHUS requires the fulfillment of the classical triad (microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure) with a positive gene mutation or antibodies to complement factors. However, absence of these mutations or antibodies, as in the presented case, do not exclude the diagnosis. The early diagnosis of aHUS is necessary for treatment with eculizumab, a monoclonal antibody against C5 to block the terminal complement cascade. Kidney biopsy can be helpful in equivocal cases especially if it shows only the typical changes of malignant hypertension which essentially rules out aHUS. Hypertension with concurrent TMA is treated with strict BP control which is often enough to resolve TMA features and restores renal function, at least partially. On the contrary, aHUS causing severe HTN needs more sophisticated testing and blockade of the terminal complement component to improve outcome; that's why the distinction of which one is the primary process is of utmost importance. Our case emphasizes the importance of having low threshold for testing for aHUS in patients with mHTN and TMA, especially in African American patients where malignant HTN is known to happen more commonly, and to notice the subtle hints that may help in this distinction, such as profound hemolysis or thrombocytopenia out of proportion to what one would expect from mHTN alone. Early recognition of aHUS may save a patient's kidney. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nephrotic syndrome associated with primary atypical hemolytic uremic syndrome

2020 ◽  
Author(s):  
Diana Carolina Bello-Marquez ◽  
John Fredy Nieto-Rios ◽  
Lina Maria Serna-Higuita ◽  
Alfonso Jose Gonzalez-Vergara
Keyword(s):  
Nephrotic Syndrome ◽  
Hemolytic Uremic Syndrome ◽  
Renal Dysfunction ◽  
Rare Disease ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Genetic Mutations ◽  
Microangiopathic Hemolytic Anemia ◽  
Uremic Syndrome ◽  
Alternative Pathway Of Complement

Abstract Primary atypical hemolytic-uremic syndrome is a rare disease characterized by non-immune microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction; it is related to alterations in the regulation of the alternative pathway of complement due to genetic mutations. The association with nephrotic syndrome is unusual. We present here a pediatric patient diagnosed with primary atypical hemolytic-uremic syndrome associated with nephrotic syndrome who responded to eculizumab treatment.

P0082CHARACTERISTICS OF ADULT PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME IN RUSSIA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kseniya Demyanova ◽  
Natalia Kozlovskaya ◽  
Yuia Korotchaeva
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Renal Dysfunction ◽  
Adult Population ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Damage ◽  
Adult Patients ◽  
Acute Episode ◽  
Plasma Therapy ◽  
Gastrointestinal Lesions ◽  
Uremic Syndrome

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is complement mediated thrombotic microangiopathy (TMA), caused by genetic abnormalities in the complement gene cluster. Information about the course of aHUS in the adult population in Russia is not enough accumulated. This study presents the characteristics of Russian adult patients (pts) with aHUS. Aim To assess the characteristics of adult pts with aHUS in Russia. Method statistical analysis of retrospective and prospective data The study included 243 pts with acute TMA (microangiopathic hemolytic anemia, thrombocytopenia, decreased haptoglobin and / or blood schizocytosis, kidney damage) from different regions of Russia. All patients were tested for ADAMTS-13 activity, and there were no accidents of TTP in our study. Cases of acute TMA associated with pregnancy and childbirth (n=134), systemic diseases (n=10), anticancer drugs treatment (n=1) and sepsis (n=13) were excluded. 85 pts with diagnosis of aHUS were selected for further analysis. Results Characteristics of pts are presented in table 1. The average age at the time of acute episode was 32.4 years, the disease was equally common among men and women. Relapsing course was rare (n=11, 13%), the maximum number of relapses – 5. In the debut, 67.8% of pts had signs of kidney damage, in 21% - gastrointestinal tract, 4.8% - CNS, 4.8% - pulmonary thromboembolism, 1.6% - visual impairment. During the acute episode, extrarenal manifestations were detected in 70% of pts, while in 38 cases (44.7%), multiple organ failure (MOF) developed with simultaneous damage from 3 to 7 organs. The most commonly observed symptoms of gastrointestinal lesions (n = 39, 45%), CNS (n = 32, 37%), heart (n = 18, 21%), less often - the organ of vision (n = 10, 12%). Kidney damage was characterized by the development of AKI in 70%, in the rest - urinary syndrome, arterial hypertension, the initial signs of renal dysfunction in various combinations. A morphological examination of kidney was performed in 40 pts (kidney biopsy - 35, autopsy - 5): acute TMA was detected in 28 pts (70%), chronic TMA - in 7 (17.5%), a combination of acute and chronic TMA - in 2 (5%), a combination of IgA-nephropathy and TMA - in 1 case (2.5%) and in 2 patients a membrane-proliferative glomerulonephritis pattern with TMA. Genetic analysis was performed in 19 pts (22%), in 7 of which (37%) identified gene variants associated with the development of aHUS (C3 in 3 pts, CFHR5 in 2 pts, CFH in 2, in 1 case - MCP and in 1-DGKE). In addition, variants of genes of the complement system with an unclear clinical value were found in all pts (n = 19). 72% of pts (n = 61) needed renal replacement therapy, almost all pts received plasma therapy (83%) and anticoagulants (85%). Only 13 pts (15%) received complement-blocking therapy with eculizumab. In the outcome of the acute episode in 12 cases (14%) renal function fully recovered, in 20 pts (23%) signs of renal dysfunction persisted (CKD 2–4 stages), 53 pts (62.3%) reached ESRD, 10 pts died (12%). Conclusion The features of aHUS in our cohort were: 1. Severe course with the development of MOF in 45% of cases 2. High frequency of ESRD in the outcome of aHUS (62.3%) 3. The incidence of genetic mutations (37%) is comparable to foreign cohorts

scholarly journals Aliskiren as an adjunct therapy for atypical hemolytic uremic syndrome

2019 ◽  
Vol 13 (1) ◽  
pp. 39-41 ◽  
Author(s):  
Richard A Plasse ◽  
Robert Nee ◽  
Stephen W Olson
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Refractory Hypertension ◽  
Antihypertensive Medications ◽  
Adjunct Treatment ◽  
Renin Inhibitors ◽  
Uremic Syndrome ◽  
Stage Renal Disease

Abstract Direct renin inhibitors (DRIs) block the activation of the alternative complement pathway in vitro and could be a treatment option for refractory hypertension in atypical hemolytic uremic syndrome (aHUS). A 20-year-old male presented with primary aHUS complicated by end-stage renal disease and refractory malignant hypertension despite being on five antihypertensive medications at maximum dose. Only a partial response was achieved with aliskiren and eculizumab, but after increasing aliskiren to a supratherapeutic dose, antihypertensive medication was reduced, platelets increased, C3 increased and epoetin alfa requirement decreased. DRI may be an adjunct treatment for malignant hypertension associated with aHUS.

Atypical Hemolytic–Uremic Syndrome in a Child Presenting With Malignant Hypertension

2011 ◽  
Vol 52 (2) ◽  
pp. 183-186 ◽  
Author(s):  
Alisha Totina ◽  
Franca Iorember ◽  
Samir S. El-Dahr ◽  
Ihor V. Yosypiv
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Uremic Syndrome

scholarly journals C3 Glomerulopathy and Atypical Hemolytic Uremic Syndrome: Two Important Manifestations of Complement System Dysfunction

2018 ◽  
Vol 8 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Ravneet Bajwa ◽  
John A. DePalma ◽  
Taimoor Khan ◽  
Anmol Cheema ◽  
Sheila A. Kalathil ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Uremic Syndrome ◽  
Renal Dysfunction ◽  
Female Patient ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Injury ◽  
C3 Glomerulopathy ◽  
Kidney Involvement ◽  
Uremic Syndrome

The advances in our understanding of the alternative pathway have emphasized that uncontrolled hyperactivity of this pathway causes 2 distinct disorders that adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome (aHUS), renal dysfunction occurs along with thrombocytopenia, anemia, and target organ injury to multiple organs, most commonly the kidney. On the other hand, in the so-termed C3 glomerulopathy, kidney involvement is not associated with thrombocytopenia, anemia, or other system involvement. In this report, we present 2 cases of alternative pathway dysfunction. The 60-year-old female patient had biopsy-proven C3 glomerulopathy, while the 32-year-old female patient was diagnosed with aHUS based on renal dysfunction, thrombocytopenia, anemia, and normal ADAMTS-13 level. The aHUS patient was successfully treated with the monoclonal antibody (eculizumab) for complement blockade. The patient with C3 glomerulopathy did not receive the monoclonal antibody. In this patient, management focused on blood pressure and proteinuria control with an angiotensin-converting enzyme inhibitor. This article focuses on the clinical differences, pathophysiology, and treatment of aHUS and C3 glomerulopathy.

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