Introduction
Atypical Hemolytic Uremic Syndrome Differential Diagnosis in a Young Patient Post-Breast Implant Surgery and upper respiratory tract infection
History of Presenting Illness
Welcome. Your patient today is Amanda S.
Amanda S. is a 34-year-old woman with no prior history of chronic illnesses. She underwent breast-implant surgery with liposculpture a year ago, which was uneventful. Four months later post-surgery, she developed an upper respiratory tract infection. Approximately three weeks after recovering from the upper respiratory infection, she developed severe headaches and hypertensive crises, requiring multiple emergency department visits. She was diagnosed with hypertension and started on olmesartan 40 mg daily, amlodipine 5 mg daily, and bisoprolol 5 mg daily.
At six months post-surgery, Amanda was referred to the cardiology department for outpatient follow-up due to persistent hypertension and worsening renal function. After observing a significant elevation of her creatinine levels, the cardiologist referred her to the nephrology department for further evaluation.
Despite medical management with antihypertensive agents ( including olmesartan, amlodipine, and bisoprolol), Amanda's renal function began to deteriorate, with serum creatinine rising to 2.21 mg/dL. Her kidney function worsened progressively, leading to end-stage kidney disease (ESKD), necessitating dialysis. She also developed severe anemia (hemoglobin (Hgb) 6.9 g/dL [range: 12–16 g/dL]), requiring erythropoietin-stimulating agents (ESAs) a month after commencing dialysis.
Her renal biopsy revealed significant endothelins, a finding suggestive of vascular injury. There are serious concerns about the etiology of her renal deterioration despite blood pressure (BP) control. Amanda is visibly distressed and reports persistent fatigue, loss of appetite, and ongoing concerns about her kidney disease.
Medical history: new-onset hypertension, with altered renal function and progression to end-stage chronic kidney disease (ESKD)
Surgical history: breast implant surgery, liposculpture (2024)
Current medications: olmesartan, amlodipine, bisoprolol.
Family and Social History
Amanda is single and lives with her parents and her younger sister. She does not smoke but is a social drinker (3 glasses of wine per week), and has no illicit drug use. There is no significant family history of renal disease; she has one distant cousin with suspected renal artery stenosis. Allergies: no known drug allergies.
Consultation
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Full transcript below
Transcript · When did you first start noticing problems?
Doctor: Let’s start with when you first started noticing problems.
Amanda: Yes, it all started suddenly—out of nowhere. I have always been healthy. Last year, I had breast implant surgery, and four months later, I had a cold. I never had any other health problems. However, about three weeks after recovering from the cold, I began having terrible headaches, and my blood pressure would shoot up. I even ended up in the emergency room a couple of times.
Doctor: And before that, you were generally healthy?
Amanda: Yes, I was.
Doctor: Amanda, I want to ask a few focused questions about your medications. These will help us understand if any issues affect how well the treatments work or contribute to your kidney disease.
Doctor: Do you take all your prescribed medications every day as directed?
Amanda: I try to, but sometimes I forget.
Doctor: How often would you say you miss a dose—once a week, more often?
Amanda: Probably once or twice a week, especially on stressful days.
Doctor: Do you take your medications at the same time each day, such as morning or evening?
Amanda: I try to take them in the morning, but sometimes I forget until later.
Doctor: Have you noticed any side effects from your medications, such as fatigue, dizziness, swelling, or gastrointestinal problems?
Amanda: I feel very tired all the time, but I haven’t had any other major side effects.
Doctor: Do you feel your medications are helping you, or do you ever question whether they’re necessary or too many?
Amanda: I sometimes wonder, especially because I still feel unwell. And it also feels like a lot to keep track of.
Doctor: Do you take any over-the-counter medications, supplements, or herbal remedies that haven’t been prescribed?
Amanda: No, I’ve been careful to stick to only what my doctors prescribe.
Doctor: Alright, thank you, Amanda.
Transcript · Tell me about your lifestyle
Doctor: Tell me about your lifestyle, Amanda. What does a typical day look like for you?
Amanda: I’m a fitness instructor, so I spend most of my day teaching classes, working one-on-one with clients, and planning workout routines. It’s pretty active, and I’m usually on my feet all day.
Doctor: That sounds busy and demanding. How have your treatments and appointments impacted your routine?
Amanda: Honestly, it’s been tough. During the most critical phase of the disease, when I needed hemodialysis and was very swollen, I completely stopped my activities. I’ve had to cut back on work, and my schedule feels completely out of sync. Whenever I need to make these clinic visits, it is hard to plan my day, and I’m constantly worried about fitting everything in.
Doctor: How important is having more flexibility in your schedule?
Amanda: It’s really important. I’d love to have fewer disruptions so I could focus on my clients and maybe even get back to my workouts.
Tests
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ADAMTS13 activity
Antibody testing
Comprehensive Metabolic and Hematologic Panel
Genetic testing
Renal biopsy
Serology and Rheumatology
Diagnoses
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Existing Diagnoses
| Name | Start date | End date |
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Decisions
Medication selection · non-medication orders.
Existing Prescriptions
Olmesartan
Dose: 40 mg · Route: oral · Frequency: once daily
Amlodipine
Dose: 5 mg · Route: oral · Frequency: once daily
Bisoprolol
Dose: 5 mg · Route: oral · Frequency: once daily
Folic acid
Dose: 5 mg · Route: oral · Frequency: once daily
Calcitriol
Dose: 0.25 mcg · Route: oral · Frequency: once daily
ESAs
Dose: 100 U/kg · Route: subcutaneous · Frequency: thrice weekly
B-complex vitamins
Dose: 1 tablet · Route: oral · Frequency: once daily
Medication Selection
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Non-Medication Orders
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Vaccinations
Patient education
Referral to a breast surgeon for potential implant removal
Case Review
Amanda Smith, a 34-year-old woman, presented with a recent history of hypertension, anemia, and renal insufficiency, requiring dialysis for renal failure following breast implant surgery and an upper respiratory tract infection. Despite her renal insufficiency, she maintained normal urine output and had no gastrointestinal problems. A renal biopsy revealed significant endotheliitis, prompting further evaluation for autoimmune syndromes and TMA. The temporal association with her breast implant surgery and upper respiratory tract infection raised suspicion of an immune-mediated process, possibly exacerbating the underlying complement dysregulation.
Blood tests revealed evidence of hemolytic anemia, renal dysfunction, and mild thrombocytopenia, supporting the diagnosis of aHUS. Subsequent genetic testing identified a heterozygous pathogenic mutation in the C3 gene (NM_000064.4 (C3).193A>C;p. (Lys65Gln)), confirming the diagnosis of aHUS.
Given her condition, treatment with a C5 inhibitor was deemed necessary to address ongoing complement-mediated damage. Ravulizumab was selected due to its extended dosing interval, which aligned with Amanda’s active lifestyle and her need for flexibility as a fitness instructor.
This case highlights the importance of individualized therapeutic strategies in rare conditions such as aHUS. Although several therapeutic options exist, the faculty author selected ravulizumab over eculizumab based on its long dosing interval and its ability to effectively, safely, and sustainably address the underlying complement dysregulation.
INTRODUCTION
Atypical hemolytic uremic syndrome (aHUS) is a severe and life-threatening form of thrombotic microangiopathy (TMA) that primarily affects the kidneys. Without treatment, up to two-thirds of patients progress to end-stage renal disease (ESRD) shortly after onset or during relapses, underscoring the devastating nature of this condition. Rapid and accurate diagnosis, along with timely initiation of treatment, is now critical for optimizing the prognosis of aHUS patients .
SYMPTOMS AND CLINICAL PRESENTATION
The onset of aHUS is typically sudden, with children presenting with pallor, poor feeding, and edema, while adults often report fatigue and distress. Most patients display the classic triad of hemolytic uremic syndrome (HUS): anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelet count 30,000–60,000/mm³), and renal insufficiency .
Severe hypertension is common, potentially leading to cardiac failure or neurological complications such as seizures . Extrarenal manifestations, observed in 20% of patients, include CNS involvement, myocardial infarction, and distal ischemic gangrene. Rarely, patients present with life-threatening multivisceral failure due to diffuse TMA. In some cases, aHUS may develop progressively, with subclinical anemia, fluctuating thrombocytopenia, and preserved renal function before progressing to more severe disease .
DIAGNOSIS
Diagnosing aHUS involves ruling out secondary causes of thrombotic microangiopathy . Thrombocytopenia together with schistocytes observed on a peripheral blood smear, confirming microangiopathic hemolysis, should prompt further diagnostic testing , including ADAMTS13 activity assays to exclude TTP (severe deficiency <10%) and stool cultures or PCR testing to rule out Shiga toxin-producing E. coli (STEC) HUS . If ADAMTS13 activity is >5–10% and STEC-HUS has been excluded, there is a high suspicion of complement-mediated aHUS. Genetic testing may assist with prognosis and family counseling, it is not required for diagnosis, and treatment should not be delayed while awaiting results . In some cases, Kidney biopsy may aid in diagnosing TMA as the cause of renal impairment, but histological findings are nonspecific . Serial monitoring of serum creatinine and urinalysis for proteinuria troponin levels, and liver enzymes is essential for managing patients .
TREATMENT
The traditional treatment for atypical hemolytic uremic syndrome (aHUS) was therapeutic plasma exchange (TPE), which aimed to remove pathogenic factors and restore normal complement regulation. However, only about 30% of patients responded to TPE, and even among responders, organ recovery and long-term outcomes were poor. While TPE may still play a role in cases linked to factor H or factor I autoantibodies, its limited efficacy highlighted the need for more targeted approaches .
The introduction of complement-blocking therapies has transformed aHUS management. These C5 inhibitors prevent the formation of the terminal complement complex. Prompt initiation of complement inhibitors, such as ravulizumab, is essential for achieving complete TMA response and hematologic normalization in the majority of patients, as demonstrated in pivotal trials . Early initiation is crucial for optimal outcomes .
PROGNOSIS
The prognosis of aHUS varies by genotype and age, with mutations such as CFH having the worst outcomes and MCP mutations the best . Without complement-targeted therapy, up to 67% of adults and nearly half of children progress to ESRF (End-Stage Renal Failure) or death within 3–5 years. CFI, C3, CFB, and THBD mutations also carry a high risk of ESRF within the first year. Anti-CFH antibodies further worsen outcomes, with 35%–60% reaching ESRF within three years. Advances in early diagnosis and therapies like eculizumab and ravulizumab have significantly improved outcomes and reducing ESRF risk, ushering in a new era for aHUS management .
CONCLUSION Summary
Advances in understanding and treating aHUS have significantly improved outcomes, reducing mortality and ESRF rates through early diagnosis and complement-targeting therapies .
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Atypical Hemolytic Uremic Syndrome Differential Diagnosis in a Young Patient Post-Breast Implant Surgery and upper respiratory tract infection · Amanda S.
Faculty — Gustavo Ferreira Da Mata, MD
Supporter — Alexion, AstraZeneca Rare Disease