Atypical Hemolytic Uremic Syndrome

1. Disease Information (concise overview; current understanding)

Atypical hemolytic uremic syndrome is a complement-mediated thrombotic microangiopathy (TMA) characterized clinically by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and end-organ injury—most often acute kidney injury. (java2024atypicalhemolyticuremic pages 1-2, dixon2024ravulizumabinatypical pages 1-2)

Recent clinical reviews emphasize that aHUS is “a prototypical complement-mediated thrombotic microangiopathy (TMA)” and that it occurs due to endothelial injury from overactivation of the alternative complement pathway, driven by either genetic variants or acquired autoantibodies. (java2024atypicalhemolyticuremic pages 1-2)

Direct abstract quote (definition/etiology): - Java (Dec 2024, Hematology): “aHUS occurs due to endothelial injury resulting from overactivation of the alternative pathway of the complement system. The etiology… is either a genetic mutation… or an acquired deficiency due to autoantibodies.” (java2024atypicalhemolyticuremic pages 1-2)

2. Etiology

2.1 Disease causal factors

Primary mechanism: Dysregulated activation of the alternative complement pathway, often conceptualized as impaired regulation of the complement amplification loop (loss-of-function in regulators) or gain-of-function in activators. (java2024atypicalhemolyticuremic pages 1-2, musalem2025tentipsfor pages 1-2)

Genetic vs acquired causes: - Genetic predisposition via variants in complement genes (examples: CFH, CFI, CD46/MCP, C3, CFB, THBD) and complement-related loci (e.g., CFHR rearrangements). (maria2025recommendationsfordiagnosis pages 5-7, java2024atypicalhemolyticuremic pages 1-2) - Acquired predisposition via autoantibodies, especially anti–factor H (anti-FH / anti-CFH) antibodies (often linked to CFHR1–CFHR3 deletions). (java2024atypicalhemolyticuremic pages 1-2, maria2025recommendationsfordiagnosis pages 7-10)

2.2 Risk factors (genetic; triggers as “environmental/clinical exposures”)

Multi-hit model / triggers: Multiple expert sources describe a “double-hit” or “multi-hit” model in which a genetic or acquired complement-control defect often requires a precipitating trigger (e.g., infection, pregnancy, surgery, autoimmune disease, transplantation, certain drugs) to manifest clinically. (cole2025updateinthe pages 1-3, bogdan2025atypicalhemolyticuremic pages 2-4, java2024atypicalhemolyticuremic pages 1-2)

Examples of triggers (from recent review/consensus): infections, pregnancy-related complications, malignancy, autoimmune diseases, surgery, transplantation, and other secondary TMA contexts. (musalem2025tentipsfor pages 1-2, cole2025updateinthe pages 1-3)

2.3 Protective factors

No explicit genetic or environmental protective factors were identified in the retrieved evidence excerpts. (Not available in this run.)

2.4 Gene–environment interaction

The “multi-hit” framing implies gene–environment/clinical interactions: genetically predisposed individuals may remain asymptomatic until an external trigger (infection/pregnancy/surgery/etc.) provokes complement-mediated endothelial injury and TMA. (java2024atypicalhemolyticuremic pages 1-2, bogdan2025atypicalhemolyticuremic pages 2-4)

3. Phenotypes (clinical, laboratory, QoL)

3.1 Core phenotype (TMA triad)

• MAHA: anemia with hemolysis markers (elevated LDH, low haptoglobin, schistocytes; Coombs-negative). (maria2025recommendationsfordiagnosis pages 5-7, bogdan2025atypicalhemolyticuremic pages 7-9)
• Thrombocytopenia. (java2024atypicalhemolyticuremic pages 1-2, dixon2024ravulizumabinatypical pages 1-2)
• Organ injury: most commonly kidney (acute kidney injury, reduced eGFR, creatinine rise), but can be multi-organ. (dixon2024ravulizumabinatypical pages 1-2, bogdan2025atypicalhemolyticuremic pages 5-7)

3.2 Renal phenotype (primary)

Renal involvement is emphasized as predominant: “acute kidney injury is almost always seen,” and may be severe, including dialysis dependence; some presentations can be kidney-limited TMA detectable only by biopsy (with minimal hematologic manifestations). (java2024atypicalhemolyticuremic pages 1-2)

Quantitative renal outcome statements reported in a recent review excerpt include AKI in 60–70% and up to 50% progressing to ESKD, with frequent dialysis/RRT requirement. (bogdan2025atypicalhemolyticuremic pages 4-5)

3.3 Extrarenal manifestations (selected; with frequencies where available)

Evidence supports a broad extrarenal spectrum including neurologic, cardiac, GI, pulmonary, dermatologic, and ocular involvement. (bogdan2025atypicalhemolyticuremic pages 5-7)

• Neurologic involvement: reported 8–48% with a registry estimate 27.2%; manifestations include seizures, encephalopathy/altered consciousness, hemiparesis, and visual impairment. (bogdan2025atypicalhemolyticuremic pages 5-7)
• Cardiac involvement: in one review excerpt, cardiovascular involvement reported up to 43% in pediatric and 3–10% in adults; includes cardiomyopathy, intracardiac thrombi, and other dysfunction. (bogdan2025atypicalhemolyticuremic pages 4-5)
• Pulmonary: respiratory failure requiring mechanical ventilation reported up to 21% in pediatric patients, often secondary to pulmonary edema/fluid overload/cardiac dysfunction. (bogdan2025atypicalhemolyticuremic pages 5-7)
• Ocular: ocular involvement reported ~4%, potentially with acute vision loss. (bogdan2025atypicalhemolyticuremic pages 5-7)
• Gastrointestinal: diarrhea reported ~50% overall and >80% in anti–factor H antibody-associated aHUS; severe complications can include pancreatitis, GI bleeding, and intestinal perforation. (bogdan2025atypicalhemolyticuremic pages 5-7)

3.4 Quality of life (QoL) impact

• aHUS can cause significant functional impairment; Java’s clinical case vignette describes “severe ongoing fatigue requiring assistance with activities of daily living” and inability to work during recovery. (java2024atypicalhemolyticuremic pages 1-2)
• In ravulizumab trials, fatigue improvement (FACIT-F) achieved by 26 weeks was maintained through 2 years. (dixon2024ravulizumabinatypical pages 1-2)

3.5 Suggested HPO terms (examples; not exhaustive)

(These are ontology mappings proposed for knowledge-base structuring; they are not asserted to be provided verbatim by the cited papers.) - Hematologic/TMA: Schistocytosis; Hemolytic anemia; Thrombocytopenia. (maria2025recommendationsfordiagnosis pages 5-7, bogdan2025atypicalhemolyticuremic pages 7-9) - Renal: Acute kidney injury; Proteinuria; Hematuria; Hypertension; End-stage renal disease; Dialysis-dependent renal failure. (bogdan2025atypicalhemolyticuremic pages 7-9, bogdan2025atypicalhemolyticuremic pages 4-5) - Neurologic: Seizures; Encephalopathy; Stroke; Altered consciousness. (java2024atypicalhemolyticuremic pages 1-2, bogdan2025atypicalhemolyticuremic pages 5-7) - Cardiac: Cardiomyopathy; Myocardial infarction; Intracardiac thrombosis. (bogdan2025atypicalhemolyticuremic pages 4-5, java2024atypicalhemolyticuremic pages 1-2) - GI: Diarrhea; Pancreatitis; Gastrointestinal hemorrhage. (bogdan2025atypicalhemolyticuremic pages 5-7) - Dermatologic/vascular: Digital gangrene. (java2024atypicalhemolyticuremic pages 1-2)

4. Genetic / Molecular Information

4.1 Causal genes (core set supported in retrieved evidence)

Commonly evaluated genes include CFH, CFI, CD46 (MCP), C3, CFB, CFHR genes (copy-number changes/rearrangements), CFH-CFHR hybrid genes, DGKE, THBD. (maria2025recommendationsfordiagnosis pages 5-7, java2024atypicalhemolyticuremic pages 1-2)

Quantitative genetic architecture: - “Approximately 60–70% of patients with aHUS have identifiable genetic or acquired abnormalities in complement-regulating components,” and genetic mutations are detected in ~60% in one review. (bogdan2025atypicalhemolyticuremic pages 2-4) - VUS findings are common: “In approximately 30% to 40%… a genetic variant of uncertain significance (VUS) may be identified.” (java2024atypicalhemolyticuremic pages 1-2)

4.2 Variant types / functional consequences (high-level)

• Loss-of-function in complement regulators (e.g., CFH/CFI/CD46) and gain-of-function in activators (e.g., C3/CFB) are emphasized as etiologic themes. (musalem2025tentipsfor pages 1-2)

4.3 Gene-level frequency estimates (from review excerpts)

• CFH: ~20–30% (and in one table range up to ~20–45%). (bogdan2025atypicalhemolyticuremic pages 2-4)
• CFI: ~5–10%. (bogdan2025atypicalhemolyticuremic pages 4-5, bogdan2025atypicalhemolyticuremic pages 2-4)
• C3: ~2–10%. (bogdan2025atypicalhemolyticuremic pages 2-4)
• THBD: ~3–5%. (bogdan2025atypicalhemolyticuremic pages 4-5)
• CFB: rare (<1% in one excerpt). (bogdan2025atypicalhemolyticuremic pages 4-5)

4.4 Anti–factor H autoantibodies and CFHR deletions

• Anti-FH/anti-CFH autoantibodies: ~10% in US/European cohorts, up to ~50% in some Indian cohorts. (java2024atypicalhemolyticuremic pages 1-2)
• Strong association with CFHR1–CFHR3 deletions: one consensus statement cites CFHR1–CFHR3 deletion in 87% of antibody-positive pediatric cases. (maria2025recommendationsfordiagnosis pages 5-7, maria2025recommendationsfordiagnosis pages 7-10)

4.5 Modifier genes / oligogenicity

About 10% of affected patients carry >1 variant or risk polymorphism (supporting additive/oligogenic effects). (java2024atypicalhemolyticuremic pages 1-2)

4.6 Penetrance and expressivity

• Overall penetrance of genetic predisposition is reported as ~50%, consistent with trigger dependence. (java2024atypicalhemolyticuremic pages 1-2)
• Gene-specific penetrance examples: CFH ~50%, MCP/CD46 ~20% (with MCP often associated with better prognosis). (bogdan2025atypicalhemolyticuremic pages 2-4)

4.7 Epigenetic information / chromosomal abnormalities

No specific epigenetic mechanisms were identified in the retrieved excerpts. (Not available in this run.)

5. Environmental Information (triggers and exposures)

aHUS is not classically caused by a single environmental agent, but multiple clinical exposures can trigger disease in predisposed individuals, including infection and pregnancy-associated complications; malignancy and other inflammatory/immune contexts are described as triggers in CM-TMA literature. (musalem2025tentipsfor pages 1-2, cole2025updateinthe pages 1-3)

Infectious triggers: STEC infection can coexist and may precipitate complement-mediated aHUS in genetically predisposed individuals; thus STEC positivity does not exclude aHUS in atypical/severe courses. (mortari2025shigatoxinproducingescherichia pages 1-2)

Lifestyle/toxin exposures: Not supported by the retrieved evidence excerpts (not asserted).

6. Mechanism / Pathophysiology

6.1 Causal chain (current consensus)

1) Genetic variants or acquired autoantibodies reduce control of the alternative complement pathway amplification loop. (java2024atypicalhemolyticuremic pages 1-2, musalem2025tentipsfor pages 1-2) 2) Uncontrolled complement activation leads to endothelial injury (and downstream microthrombi formation). (java2024atypicalhemolyticuremic pages 1-2) 3) Microvascular thrombosis causes MAHA (shear-related schistocytes), thrombocytopenia (consumption), and ischemic organ injury (kidney predominant). (maria2025recommendationsfordiagnosis pages 5-7)

6.2 Cellular and tissue targets

The proximate site of injury is the microvascular endothelium with consequent small-vessel thrombosis; renal microvasculature and glomerular capillaries are highlighted by renal-dominant clinical manifestations. (maria2025recommendationsfordiagnosis pages 5-7, dixon2024ravulizumabinatypical pages 1-2)

Suggested Cell Ontology (CL) terms (examples): endothelial cell; platelet; erythrocyte (RBC). (maria2025recommendationsfordiagnosis pages 5-7)

Suggested GO biological process terms (examples): complement activation (alternative pathway), regulation of complement activation, platelet aggregation, blood coagulation, endothelial cell injury/activation.

6.3 Biomarkers / functional assays (recent developments)

Because no single definitive diagnostic test exists, emerging functional complement assays are discussed as adjuncts to demonstrate complement hyperactivity (e.g., modified Ham assay and endothelial C5b-9 deposition assays). (cole2025updateinthe pages 1-3)

7. Anatomical Structures Affected

7.1 Organ level (UBERON suggestions)

• Kidney (primary): acute kidney injury, proteinuria/hematuria, reduced eGFR; frequent progression to CKD/ESKD in severe cases. (bogdan2025atypicalhemolyticuremic pages 4-5, java2024atypicalhemolyticuremic pages 1-2)
• Brain / CNS: seizures, encephalopathy, stroke. (java2024atypicalhemolyticuremic pages 1-2, bogdan2025atypicalhemolyticuremic pages 5-7)
• Heart: cardiomyopathy, myocardial infarction, intracardiac thrombi. (bogdan2025atypicalhemolyticuremic pages 4-5, java2024atypicalhemolyticuremic pages 1-2)
• Gastrointestinal tract / pancreas / liver: diarrhea, pancreatitis, transaminitis/hepatitis. (bogdan2025atypicalhemolyticuremic pages 5-7, java2024atypicalhemolyticuremic pages 1-2)
• Lung: pulmonary edema/respiratory failure in severe cases. (bogdan2025atypicalhemolyticuremic pages 5-7)

7.2 Tissue and cell level

Microvascular beds are implicated (TMA with microvascular occlusion and endothelial injury). (maria2025recommendationsfordiagnosis pages 5-7)

7.3 Subcellular level

Not explicitly described in retrieved excerpts.

8. Temporal Development

8.1 Onset

aHUS can present across the lifespan (pediatric to adult), and onset is often acute/subacute in the setting of a trigger. (bogdan2025atypicalhemolyticuremic pages 2-4, maria2025recommendationsfordiagnosis pages 3-5)

8.2 Progression

Without prompt targeted therapy, disease may progress to chronic kidney disease/ESKD and multi-organ morbidity. (dixon2024ravulizumabinatypical pages 1-2, bogdan2025atypicalhemolyticuremic pages 4-5)

8.3 Relapse/recurrence

Relapse risk is linked to underlying genetic/acquired etiology; long-term discontinuation decisions remain complex and are a focus of hematology guidance. (java2024atypicalhemolyticuremic pages 1-2, musalem2025tentipsfor pages 1-2)

9. Inheritance and Population

9.1 Epidemiology (statistics)

A systematic review of population-based studies reported: - All-ages annual incidence: 0.23–1.9 per million per year. (yan2020epidemiologyofatypical pages 1-2) - ≤20 years annual incidence: 0.26–0.75 per million per year. (yan2020epidemiologyofatypical pages 1-2) - Prevalence ≤20 years: 2.2–9.4 per million; single all-ages prevalence estimate: 4.9 per million. (yan2020epidemiologyofatypical pages 1-2)

Extrarenal complications frequency: extrarenal complications can occur in up to ~20% in some epidemiologic descriptions. (yan2020epidemiologyofatypical pages 1-2, bogdan2025atypicalhemolyticuremic pages 7-9)

9.2 Inheritance pattern

The retrieved evidence supports a genetic predisposition with incomplete penetrance rather than a single uniform Mendelian pattern; both dominant and recessive mechanisms can exist across genes/variants, and acquired autoantibodies also contribute. Because explicit mode(s) of inheritance were not enumerated in the provided excerpts, a detailed AD/AR breakdown is not asserted here. (java2024atypicalhemolyticuremic pages 1-2, bogdan2025atypicalhemolyticuremic pages 2-4)

9.3 Population demographics

• Children: roughly equal sex distribution.
• Adults: higher female frequency. (yan2020epidemiologyofatypical pages 1-2)

10. Diagnostics

10.1 Clinical tests and biomarkers

Diagnostic work-up centers on confirming TMA and excluding close mimics: - Hemolysis labs: LDH↑, schistocytes, haptoglobin↓, Coombs negative, indirect bilirubin↑. (maria2025recommendationsfordiagnosis pages 5-7) - Platelets decreased; creatinine elevated / AKI. (java2024atypicalhemolyticuremic pages 1-2)

10.2 Differential diagnosis (must exclude)

• TTP: exclude using ADAMTS13 activity; severe deficiency (≤10%) supports TTP, while normal/above 10% supports non-TTP TMA context. (maria2025recommendationsfordiagnosis pages 5-7, bogdan2025atypicalhemolyticuremic pages 7-9)
• STEC-HUS: exclude using Shiga toxin PCR/stool culture. (maria2025recommendationsfordiagnosis pages 5-7)

10.3 Complement testing (caveats)

• Plasma C3 may be low but low C3 occurs in <20%; normal C3 does not rule out aHUS. (maria2025recommendationsfordiagnosis pages 5-7)

10.4 Genetic testing strategy

Expert sources recommend complement gene panel testing plus autoantibody testing in suspected aHUS, including evaluation for CFHR deletions/rearrangements (e.g., by MLPA when NGS is negative) and work-up of VUS by antigenic/functional assays. (java2024atypicalhemolyticuremic pages 1-2, maria2025recommendationsfordiagnosis pages 7-10)

11. Outcome / Prognosis

11.1 Renal outcomes

aHUS can lead to CKD/ESKD without timely treatment; review data cite AKI common and up to 50% ESKD in some cohorts. (bogdan2025atypicalhemolyticuremic pages 4-5)

11.2 Pregnancy-associated aHUS (p-aHUS) outcomes (systematic review/meta-analysis; 2025, searches through Mar 2024)

In 10 studies (386 pregnancies in 380 patients): - Dialysis required: 66.6%. (meena2025kidneyandpregnancy pages 1-2) - ESKD: 25%. (meena2025kidneyandpregnancy pages 1-2) - Maternal mortality: 5%. (meena2025kidneyandpregnancy pages 1-2) - Obstetric complications: preeclampsia 36.4%, HELLP 29.7%. (meena2025kidneyandpregnancy pages 1-2) - Eculizumab benefit: reduced CKD/ESKD risk with pooled risk ratio 0.20 (95% CI 0.09–0.44). (meena2025kidneyandpregnancy pages 1-2)

12. Treatment

12.1 Pharmacotherapy (current standard; real-world implementation)

Terminal complement inhibition (C5 inhibitors): - Eculizumab: effective since approval in 2011; requires q2 week infusions (treatment burden noted). (dixon2024ravulizumabinatypical pages 1-2) - Ravulizumab: next-generation C5 inhibitor designed for extended dosing interval; maintenance every 4–8 weeks weight-based. (dixon2024ravulizumabinatypical pages 1-2)

Ravulizumab 2-year phase 3 outcomes (published online June 14, 2024): - Complete TMA response over 2 years: 61% (C5i-naïve adults) and 90% (C5i-naïve pediatrics). (dixon2024ravulizumabinatypical pages 1-2) - Median eGFR improvement maintained: +35 (adults) and +82.5 mL/min/1.73m² (pediatrics). (dixon2024ravulizumabinatypical pages 1-2) - Safety: “No meningococcal infections were reported” over 2 years; most AEs/SAEs occurred in the first 26 weeks. (dixon2024ravulizumabinatypical pages 1-2)

Real-world registry implementation (kidney transplant recipients switching eculizumab→ravulizumab; data cut Sep 2, 2024; published Aug 2025): - After switching, labs remained stable; no graft failures/rejections reported; in safety population (n=38), 50% had any AE, none treatment-related; no meningococcal infections or deaths reported. (gaeckler2025effectivenessandsafety pages 1-2)

12.2 Supportive care / plasma exchange

Plasma exchange historically served as primary therapy in the pre-C5 inhibitor era, and remains relevant particularly in anti–factor H autoantibody–associated disease (often combined with immunosuppression), while prompt complement inhibition is emphasized for complement-driven disease. (musalem2025tentipsfor pages 1-2)

12.3 Prevention / prophylaxis related to therapy

Prophylactic measures against infections—particularly meningococcal disease—are described as mandatory/required for patients receiving C5 inhibitors. (musalem2025tentipsfor pages 1-2)

12.4 Suggested MAXO terms (examples)

• Complement inhibitor therapy; monoclonal antibody therapy; plasma exchange (therapeutic apheresis); kidney replacement therapy (dialysis); kidney transplantation; vaccination (meningococcal).

13. Prevention

Primary prevention of genetically predisposed aHUS is not established in the retrieved evidence. Prevention is primarily tertiary in practice (prevent relapse/complications) via appropriate complement inhibition strategies, infection prophylaxis/vaccination for C5 blockade, and trigger management (e.g., pregnancy-associated risk planning, transplant risk stratification). (musalem2025tentipsfor pages 1-2, gaeckler2025effectivenessandsafety pages 1-2)

14. Other Species / Natural Disease

Not available from retrieved sources in this run; no claims made.

15. Model Organisms

Not available from retrieved sources in this run; no claims made.

Recent developments and 2023–2024 highlights (prioritized)

• 2024 ASH Hematology review (Java, Dec 2024) emphasizes systematic genetic/autoantibody testing, high VUS rate (30–40%), and clinical stratification for discontinuation decisions. (java2024atypicalhemolyticuremic pages 1-2)
• 2024 Kidney Medicine phase 3 long-term analysis (Dixon et al., published online Jun 14, 2024) provides durable 2-year efficacy/safety and sustained QoL improvements for ravulizumab in adults and children. (dixon2024ravulizumabinatypical pages 1-2)

Summary statistics and key points table

The following table consolidates high-yield identifiers, diagnostic criteria, genetic architecture, epidemiology, and treatment outcomes.

Table: This table compiles high-yield clinical, genetic, epidemiologic, treatment, and pregnancy-associated statistics for atypical hemolytic uremic syndrome from the gathered evidence. It is designed as a compact reference for a disease knowledge base or research summary.

Limitations of this evidence package

• ICD-10/ICD-11, Orphanet ORPHA, and OMIM identifiers were not explicitly present in the retrieved excerpts; therefore they are not asserted despite being likely available in external disease resources.
• Dedicated model-organism/animal-model primary literature was not retrieved in this run; therefore model organism sections are intentionally left as “not available.”

References

1. (musalem2025tentipsfor pages 1-2): Pilar Musalem. Ten tips for managing complement-mediated thrombotic microangiopathies (formerly atypical hemolytic uremic syndrome): narrative review. BMC Nephrology, Mar 2025. URL: https://doi.org/10.1186/s12882-025-04080-9, doi:10.1186/s12882-025-04080-9. This article has 3 citations and is from a peer-reviewed journal.

2. (cole2025updateinthe pages 1-3): Michael Arthur Cole. Update in the diagnosis of complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome. Hematology, 2025:164-175, Dec 2025. URL: https://doi.org/10.1182/hematology.2025000702, doi:10.1182/hematology.2025000702. This article has 2 citations and is from a peer-reviewed journal.

3. (bogdan2025atypicalhemolyticuremic pages 2-4): Razvan-George Bogdan, Paula Anderco, Cristian Ichim, Anca-Maria Cimpean, Samuel Bogdan Todor, Mihai Glaja-Iliescu, Zorin Petrisor Crainiceanu, and Mirela Livia Popa. Atypical hemolytic uremic syndrome: a review of complement dysregulation, genetic susceptibility and multiorgan involvement. Journal of Clinical Medicine, 14:2527, Apr 2025. URL: https://doi.org/10.3390/jcm14072527, doi:10.3390/jcm14072527. This article has 18 citations.

4. (dixon2024ravulizumabinatypical pages 1-2): Bradley P. Dixon, David Kavanagh, Alvaro Domingo Madrid Aris, Brigitte Adams, Hee Gyung Kang, Edward Wang, Katherine Garlo, Masayo Ogawa, Praveen Amancha, Sourish Chakravarty, Nils Heyne, Seong Heon Kim, Spero Cataland, Sung-Soo Yoon, Yoshitaka Miyakawa, Yosu Luque, Melissa Muff-Luett, Kazuki Tanaka, and Larry A. Greenbaum. Ravulizumab in atypical hemolytic uremic syndrome: an analysis of 2-year efficacy and safety outcomes in 2 phase 3 trials. Kidney Medicine, 6:100855, Aug 2024. URL: https://doi.org/10.1016/j.xkme.2024.100855, doi:10.1016/j.xkme.2024.100855. This article has 27 citations.

5. (NCT01522183 chunk 5): Atypical Hemolytic-Uremic Syndrome (aHUS) Registry. Alexion Pharmaceuticals, Inc.. 2013. ClinicalTrials.gov Identifier: NCT01522183

6. (NCT04861259 chunk 3): A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS). Hoffmann-La Roche. 2021. ClinicalTrials.gov Identifier: NCT04861259

7. (java2024atypicalhemolyticuremic pages 1-2): Anuja Java. Atypical hemolytic uremic syndrome: diagnosis, management, and discontinuation of therapy. Hematology, 2024:200-205, Dec 2024. URL: https://doi.org/10.1182/hematology.2024000543, doi:10.1182/hematology.2024000543. This article has 15 citations and is from a peer-reviewed journal.

8. (cole2025updateinthe pages 12-12): Michael Arthur Cole. Update in the diagnosis of complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome. Hematology, 2025:164-175, Dec 2025. URL: https://doi.org/10.1182/hematology.2025000702, doi:10.1182/hematology.2025000702. This article has 2 citations and is from a peer-reviewed journal.

9. (meena2025kidneyandpregnancy pages 1-2): Priti Meena, Ruju Gala, Rashmi Ranjan Das, Vinant Bhargava, Yellampalli Saivani, Sandip Panda, Alok Mantri, and Krishna Kumar Agrawaal. Kidney and pregnancy outcomes in pregnancy-associated atypical hemolytic uremic syndrome: a systematic review and meta-analysis. Medicine, 104:e41403, Jan 2025. URL: https://doi.org/10.1097/md.0000000000041403, doi:10.1097/md.0000000000041403. This article has 9 citations and is from a peer-reviewed journal.

10. (yan2020epidemiologyofatypical pages 3-5): Kevin Yan, Kamal Desai, Lakshmi Gullapalli, Eric Druyts, and Chakrapani Balijepalli. Epidemiology of atypical hemolytic uremic syndrome: a systematic literature review. Clinical Epidemiology, 12:295-305, Mar 2020. URL: https://doi.org/10.2147/clep.s245642, doi:10.2147/clep.s245642. This article has 144 citations and is from a highest quality peer-reviewed journal.

11. (maria2025recommendationsfordiagnosis pages 5-7): Helena Vaisbich Maria, Andrade Luis Gustavo Modelli de, Barbosa Maria Izabel Neves de Holan da, Castro Maria Cristina Ribeiro de, Miranda Silvana Maria Carvalho, Poli-de-Figueiredo Carlos Eduardo, Araujo Stanley de Almeida, Neto Miguel Ernandes, Penido Maria Goretti Moreira Guimarães, Sobral Roberta Mendes Lima, Neto Oreste Ferra, Neves Precil Diego Miranda de Menezes, Silva Cassiano Augusto Braga da, Barreto Fellype Carvalho, Pietrobom Igor Gouveia, and Palma Lilian Monteiro Pereira. Recommendations for diagnosis and treatment of atypical hemolytic uremic syndrome (ahus): an expert consensus statement from the rare diseases committee of the brazilian society of nephrology (comdora-sbn). Jornal Brasileiro de Nefrologia, Feb 2025. URL: https://doi.org/10.1590/2175-8239-jbn-2024-0087en, doi:10.1590/2175-8239-jbn-2024-0087en. This article has 7 citations.

12. (maria2025recommendationsfordiagnosis pages 7-10): Helena Vaisbich Maria, Andrade Luis Gustavo Modelli de, Barbosa Maria Izabel Neves de Holan da, Castro Maria Cristina Ribeiro de, Miranda Silvana Maria Carvalho, Poli-de-Figueiredo Carlos Eduardo, Araujo Stanley de Almeida, Neto Miguel Ernandes, Penido Maria Goretti Moreira Guimarães, Sobral Roberta Mendes Lima, Neto Oreste Ferra, Neves Precil Diego Miranda de Menezes, Silva Cassiano Augusto Braga da, Barreto Fellype Carvalho, Pietrobom Igor Gouveia, and Palma Lilian Monteiro Pereira. Recommendations for diagnosis and treatment of atypical hemolytic uremic syndrome (ahus): an expert consensus statement from the rare diseases committee of the brazilian society of nephrology (comdora-sbn). Jornal Brasileiro de Nefrologia, Feb 2025. URL: https://doi.org/10.1590/2175-8239-jbn-2024-0087en, doi:10.1590/2175-8239-jbn-2024-0087en. This article has 7 citations.

13. (bogdan2025atypicalhemolyticuremic pages 7-9): Razvan-George Bogdan, Paula Anderco, Cristian Ichim, Anca-Maria Cimpean, Samuel Bogdan Todor, Mihai Glaja-Iliescu, Zorin Petrisor Crainiceanu, and Mirela Livia Popa. Atypical hemolytic uremic syndrome: a review of complement dysregulation, genetic susceptibility and multiorgan involvement. Journal of Clinical Medicine, 14:2527, Apr 2025. URL: https://doi.org/10.3390/jcm14072527, doi:10.3390/jcm14072527. This article has 18 citations.

14. (bogdan2025atypicalhemolyticuremic pages 5-7): Razvan-George Bogdan, Paula Anderco, Cristian Ichim, Anca-Maria Cimpean, Samuel Bogdan Todor, Mihai Glaja-Iliescu, Zorin Petrisor Crainiceanu, and Mirela Livia Popa. Atypical hemolytic uremic syndrome: a review of complement dysregulation, genetic susceptibility and multiorgan involvement. Journal of Clinical Medicine, 14:2527, Apr 2025. URL: https://doi.org/10.3390/jcm14072527, doi:10.3390/jcm14072527. This article has 18 citations.

15. (bogdan2025atypicalhemolyticuremic pages 4-5): Razvan-George Bogdan, Paula Anderco, Cristian Ichim, Anca-Maria Cimpean, Samuel Bogdan Todor, Mihai Glaja-Iliescu, Zorin Petrisor Crainiceanu, and Mirela Livia Popa. Atypical hemolytic uremic syndrome: a review of complement dysregulation, genetic susceptibility and multiorgan involvement. Journal of Clinical Medicine, 14:2527, Apr 2025. URL: https://doi.org/10.3390/jcm14072527, doi:10.3390/jcm14072527. This article has 18 citations.

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