The roles of homocysteinemia and methylmalonic acidemia in kidney injury in atypical hemolytic uremic syndrome caused by cobalamin C deficiency

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. Methods: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. Results: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. Conclusion: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.

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Atypical Hemolytic Uremic Syndrome Presenting as Acute Heart Failure—A Rare Presentation: Diagnosis Supported by Skin Biopsy

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709619842905 ◽

2019 ◽

Vol 7 ◽

pp. 232470961984290

Author(s):

Asim Kichloo ◽

Savneek Singh Chugh ◽

Sanjeev Gupta ◽

Jay Pandav ◽

Praveen Chander

Keyword(s):

Heart Failure ◽

Skin Biopsy ◽

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

Atypical Hemolytic Uremic Syndrome ◽

Systolic Heart Failure ◽

Kidney Injury ◽

Rare Presentation ◽

History Of ◽

Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder of uncontrolled complement activation that manifests classically as anemia, thrombocytopenia, and renal failure, although extrarenal manifestations are observed in 20% of the patient most of which involving central nervous system, with relatively rare involvement of the heart. In this article, we report the case of a 24-year-old male with no history of heart disease presenting with acute systolic heart failure along with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given his presentation of thrombotic microangiopathy (TMA), along with laboratory results significant for low haptoglobin, platelets, hemoglobin, C3, C4, CH50, and normal ADAMTS13 levels, with no diarrhea and negative STEC polymerase chain reaction in stool, aHUS diagnosis was established with strong clinical suspicion, and immediate initiation of treatment was advised. Kidney biopsy to confirm diagnosis of aHUS was inadvisable because of thrombocytopenia, so the skin biopsy of a rash on his arm was done, which came to be consistent with thrombotic microangiopathy. Our case highlights a relatively rare association between aHUS and cardiac involvement, and the use of skin biopsy to support diagnosis of aHUS in patients who cannot undergo renal biopsy because of thrombocytopenia.

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Postpartum atypical hemolytic uremic syndrome: Evaluating thrombotic microangiopathy in the pregnant woman

Obstetric Medicine ◽

10.1177/1753495x20926043 ◽

2020 ◽

pp. 1753495X2092604

Author(s):

S So ◽

E Fischer ◽

M Gangadharan Komala ◽

B Bose

Keyword(s):

Acute Kidney Injury ◽

Pregnant Woman ◽

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

Post Partum ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Uremic Syndrome ◽

In Pregnancy

Acute kidney injury in women during pregnancy and the puerperium is often ascribed to hypertensive complications of pregnancy, especially pre-eclampsia. However, rarer causes, including atypical hemolytic uremic syndrome (aHUS) can be triggered by pregnancy. We present a case of a woman with post-partum acute kidney injury due to aHUS, which was successfully treated with the C5a inhibitor eculizumab. We also present a summary of the evaluation and management of thrombotic microangiopathy in pregnancy.

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Atypical Hemolytic Uremic Syndrome after ChAdOx1 nCoV-19 Vaccination in a Patient with Homozygous CFHR3/CFHR1 Gene Deletion

Nephron ◽

10.1159/000519461 ◽

2021 ◽

pp. 1-5

Author(s):

Francisco Ferrer ◽

Marisa Roldão ◽

Cátia Figueiredo ◽

Karina Lopes

Keyword(s):

Hemolytic Uremic Syndrome ◽

Alternative Pathway ◽

Atypical Hemolytic Uremic Syndrome ◽

Clinical Manifestations ◽

Kidney Injury ◽

Time Lapse ◽

Normal Activity ◽

Factor H ◽

Complement Alternative Pathway ◽

Uremic Syndrome

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) affecting the kidneys. Compared with typical HUS due to an infection from shiga toxin-producing Escherichia coli, atypical HUS involves a genetic or acquired dysregulation of the complement alternative pathway. In the presence of a mutation in a complement gene, a second trigger is often necessary for the development of the disease. We report a case of a 54-year-old female, with a past medical history of pulmonary tuberculosis, who was admitted to the emergency service with general malaise and reduction in urine output, 5 days after vaccination with ChAdOx1 nCoV-19. Laboratory results revealed microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given the clinical picture of TMA, plasma exchange (PEX) was immediately started, along with hemodialysis. Complementary laboratory workup for TMA excluded thrombotic thrombocytopenic purpura and secondary causes. Complement study revealed normal levels of factors H, B, and I, normal activity of the alternate pathway, and absence of anti-factor H antibodies. Genetic study of complement did not show pathogenic variants in the 12 genes analyzed, but revealed a deletion in gene CFHR3/CFHR1 in homozygosity. Our patient completed 10 sessions of PEX, followed by eculizumab, with both clinical and laboratorial improvement. Actually, given the short time lapse between vaccination with ChAdOx1 nCoV-19 and the clinical manifestations, we believe that vaccine was the trigger for the presentation of aHUS in this particular case.

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Atypical hemolytic uremic syndrome: A report of two cases

Bangabandhu Sheikh Mujib Medical University Journal ◽

10.3329/bsmmuj.v9i1.28954 ◽

2016 ◽

Vol 9 (1) ◽

pp. 75

Author(s):

Md. Habibur Rahman ◽

Morsheda Akhter ◽

Syed Symul Haque

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Course Of Illness ◽

Atypical Hus ◽

Excellent Outcome ◽

Uremic Syndrome ◽

Stage Renal Disease ◽

End Stage ◽

Insight Into

Hemolytic uremic syndrome (HUS) is one of the important cause of acute kidney injury in children. There is excellent outcome in patients with typical HUS but atypical HUS is associated with high mortality, risk of recurrence and may lead to end stage renal disease. We report two cases of 5 and 6 year old child having clinical & laboratory characteristics of atypical HUS. These children had a fulminant course of illness with complications involving various systems. The report provides an insight into the etio pathogenesis, diagnoses and treatment of this condition.

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Successful use of eculizumab to treat atypical hemolytic uremic syndrome in patients with inflammatory bowel disease

Thrombosis Journal ◽

10.1186/s12959-019-0207-7 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

Ramy M. Hanna ◽

Noah Merin ◽

Richard M. Burwick ◽

Lama Abdelnour ◽

Umut Selamet ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Hemolytic Uremic Syndrome ◽

Lupus Erythematosus ◽

Complement Activation ◽

Bowel Disease ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Uremic Syndrome ◽

Inflammatory Bowel ◽

Case Presentations

Abstract Background Atypical hemolytic uremic syndrome is a rare group of disorders that have in common underlying complement amplifying conditions. These conditions can accelerate complement activation that results in a positive feedback cycle. The known triggers for complement activation can be diverse and include, infection, autoimmune disease, and malignancy. Recent reports suggest that certain autoimmune and rheumatological triggers of complement activation may result in atypical hemolytic uremic syndrome that does not resolve despite treating the underlying disorder. Specifically, patients with systemic lupus erythematosus and microangiopathic hemolysis may not respond to treatment of their underlying rheumatological trigger but responded to complement blockade. Case presentations We report two patients with inflammatory bowel disease complicated by development of atypical hemolytic uremic syndrome. In both cases, patients were on treatment for inflammatory bowel disease, that was not well controlled/flaring at the time. The first patient is a male who developed Crohn’s disease and microangiopathic hemolysis at age 5 and was treated with eculizumab successfully. Discontinuation of the medication led to multiple relapses, and the patient currently is being treated with eculizumab and has normal hematological and stable renal parameters. The second patient is a 49-year-old female with Ulcerative Colitis treated with 6-Mercaptopurine. She developed acute kidney injury and microangiopathic hemolysis. Prompt diagnosis and treatment with eculizumab resulted in the recovery of kidney injury along with a complete hematological response. Conclusions These two cases are the fifth and sixth patients to be published in the literature with atypical hemolytic uremic syndrome and inflammatory bowel disease treated with complement blockade. This confirms that C5 complement blockade is effective in treating complement mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome when it is triggered in patients with inflammatory bowel disease.

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Atypical Hemolytic Uremic Syndrome following Acute Type A Aortic Dissection

Case Reports in Hematology ◽

10.1155/2020/2467953 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Eigo Ikushima ◽

Manabu Hisahara ◽

Takuya Nishijima ◽

Hikaru Uchiyama ◽

Tatsushi Onzuka ◽

...

Keyword(s):

Aortic Dissection ◽

Hemolytic Uremic Syndrome ◽

Hemolytic Anemia ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Type A ◽

Acute Type ◽

Microangiopathic Hemolytic Anemia ◽

Type A Aortic Dissection ◽

Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA)-related disease that manifests as a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is caused by uncontrolled activation of the complement system. We report the case of a 61-year-old woman with acute type A aortic dissection that subsequently developed into aHUS. The hematologic disorders underlying aHUS improved after treatment with the complement inhibitor eculizumab. It is important to consider aHUS when a patient clinically develops a triad of microangiopathic hemolytic anemia, thrombocytopenia, and an increasing creatinine level following cardiovascular surgery.

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Atypical hemolytic-uremic syndrome as one of the causes of acute kidney injury in pregnant women

Terapevticheskii arkhiv ◽

10.26442/terarkh201890628-34 ◽

2018 ◽

Vol 90 (6) ◽

pp. 28-34 ◽

Cited By ~ 1

Author(s):

N L Kozlovskaya ◽

Yu V Korotchaeva ◽

E M Shifman ◽

L A Bobrova

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Clinical Manifestations ◽

Kidney Injury ◽

Complete Recovery ◽

Multiple Organ ◽

Aim Analysis ◽

Uremic Syndrome

Obstetric atypical hemolytic uremic syndrome (aHUS) is one of the reasons for the development of acute kidney injury (AKI) and can determine the prognosis of both mother and child. Aim. Analysis of clinical manifestations, course and outcomes of obstetric aHUS. Materials and methods. 45 patients with aHUS development during pregnancy or immediately after childbirth were observed between 2011 and 2017, age from 16 to 42 years. Results and discussion. All patients had AKI (serum creatinine 521,5±388,0 µmol/l, oliguria or anuria that required initiation of hemodialysis). 93.3% pts had extrarenal manifestations of TMA with the development of multiple organ failure (MOF). The mean number of damage organs was 3,7±1,2. In all patients, the development of aHUS was preceded by obstetric complications, surgery, infection, etc. In the outcome: 53.4% women showed complete recovery of renal function, 11.1% developed CKD 4-5 stages, 35.5% had dialysis-dependent end-stage renal failure (ESDR). Maternal mortality was 23.9%. Perinatal mortality was 32.6%. The early start of eculizumab treatment (within 1-2 weeks from the onset of aHUS), compared with therapy start after 3 weeks, increased the chances of favorable outcome for mother in 5.33 times, and the chances for normalization of renal function in 48.7 times. Conclusion. Obstetric aHUS is characterized by the development of AKI in 100% of cases. In most patients, the obstetric aHUS occurs with the development of MOF. Timely diagnosis of aHUS and immediate treatment by eculizumab allows not only to save the life of patients, but also completely restore their health.

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Atypical hemolytic uremic syndrome: a brief review

Hematology Reports ◽

10.4081/hr.2017.7053 ◽

2017 ◽

Vol 9 (2) ◽

Cited By ~ 20

Author(s):

Kuixing Zhang ◽

Yuxin Lu ◽

Kevin T. Harley ◽

Minh-Ha Tran

Keyword(s):

Hemolytic Uremic Syndrome ◽

Regulatory Gene ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Regulatory Mechanisms ◽

Complement Inhibitor ◽

Loss Of Function ◽

Microangiopathic Hemolytic Anemia ◽

Uremic Syndrome ◽

Glomerular Capillaries

Atypical hemolytic uremic syndrome (aHUS) is a disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The histopathologic lesions of aHUS include thrombotic microangiopathy involving the glomerular capillaries and thrombosis involving arterioles or interlobar arteries. Extra-renal manifestations occur in up to 20% of patients. The majority of aHUS is caused by complement system defects impairing ordinary regulatory mechanisms. Activating events therefore lead to unbridled, ongoing complement activity producing widespread endothelial injury. Pathologic mutations include those resulting in loss-of-function in a complement regulatory gene (CFH, CFI, CD46 or THBD) or gain-of-function in an effector gene (CFB or C3). Treatment with the late complement inhibitor, eculizumab – a monoclonal antibody directed against C5 – is effective.

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Pregnancy associated atypical hemolytic uremic syndrome triggered by massive uterine bleeding after outpatient dilatation and evacuation

Journal of Onco-Nephrology ◽

10.1177/23993693211058192 ◽

2021 ◽

pp. 239936932110581

Author(s):

Minh-Ha Tran ◽

Patrick Penalosa ◽

Anum Hamiduzzaman ◽

Ramy Hanna

Keyword(s):

Hemolytic Uremic Syndrome ◽

Early Recognition ◽

Pregnancy Termination ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Diagnostic Laboratory ◽

Complement Inhibitors ◽

Treatment Measures ◽

Uremic Syndrome ◽

System Disorder

Background: Atypical Hemolytic Uremic Syndrome (aHUS) is a renal threatening multi-system disorder with significant hematologic findings of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. Early recognition and institution of late complement inhibitors can interrupt a cycle of progressive hemolysis and renal injury. Methods: We present an informative case of aHUS triggered by pregnancy termination. Diagnostic, laboratory, and treatment measures are reviewed. Results: Clinical evidence demonstrates immediate improvement in hemolysis, platelet consumption, and acute kidney injury following initiation of eculizumab. Conclusion: Pregnancy is a recognized trigger of aHUS and its proper management requires early recognition and institution of late complement blockade. Genetic testing can be sent for genetic counseling purposes, but initiation of treatment should neither await these results nor be discontinued when high-risk polymorphisms are absent.

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