RARE DISEASE
Hemolytic uremic syndrome
Hemolytic uremic syndrome
Hemolytic uremic syndrome
Synonyms: HUS
Synonyms: HUS
Synonyms: HUS
Drug discovery
2
drugs
With orphan designations
Overview
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Most cases (90%) are caused by Shiga toxin-producing E. coli (STEC), while 10% are atypical (aHUS) due to complement dysregulation or other triggers [1][5][6]. Organ involvement includes renal failure (61% requiring dialysis), neurologic complications (52% in adults), and cardiovascular damage [9][16].
Burden
Acute mortality: 5% in children vs. 19.8% in adults (higher with immunodeficiency/severe neurology) [9][16]
Chronic sequelae: 25–45% develop hypertension or CKD; 3–5% progress to ESRD [4][10][16]
Economic impact: $541,695/case (direct/indirect costs), including long-term renal/psychosocial care [4][9]
Therapies
STEC-HUS: Supportive care (IV rehydration, transfusion, dialysis), avoidance of antibiotics/antidiarrheals [3][6][8]
aHUS: Complement inhibitors (eculizumab/ravulizumab) with 80% efficacy; plasma exchange for refractory cases [5][6][18]
Renal replacement therapy required in 50–63% of patients; transplant considered for end-stage disease [8][10]
Categories: rare renal diseases, rare transplant-related disorders
Research Papers
2,267 drug discovery papers about Hemolytic uremic syndrome, with 5 first-in-class and 15 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,267 drug discovery papers about Hemolytic uremic syndrome, with 5 first-in-class and 15 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Sirolimus application in patients with autoimmune-associated kidney diseases based on mTORC1 activation: a preliminary exploration and future perspectives.
The mTORC1 pathway drives pathogenesis in autoimmune kidney diseases. We hypothesized that intrarenal mTORC1 activation could identify patients likely to benefit from sirolimus, irrespective of their specific diagnosis. In this prospective proof-of-concept series, we screened eight patients with active autoimmune kidney disease for mTORC1 activation by immunohistochemistry on renal biopsy. Five positive patients (staining intensity: + to +++) received sirolimus, presenting with lupus nephritis atypical hemolytic uremic syndrome (aHUS), thrombotic microangiopathy (TMA), or IgA nephropathy (IgAN) associated with lung cancer. Over a mean follow-up of 25 months, four patients exhibited improved or stable renal function. All responders demonstrated moderate-to-high (++ to +++) mTORC1 staining, whereas the single non-responder who progressed to end-stage renal disease had only weak (+) staining. Proteinuria declined to <1 g/day in most responders. Sirolimus was well-tolerated. In two patients with concurrent malignancy, sirolimus did not aggravate stable breast cancer but was discontinued due to lung adenocarcinoma progression. This study indicates that intrarenal mTORC1 activation levels may help identify patients more likely to respond to sirolimus across various autoimmune kidney diseases, warranting further investigation as a precision-medicine approach.
2026-08-12 | Protective effects of bismuth hydroxide against hemolytic uremic syndrome caused by Shiga toxin producing Escherichia coli.
Shiga toxin-producing Escherichia coli (STEC) is a major cause of foodborne disease and hemolytic uremic syndrome (HUS), a severe condition for which no specific therapies are currently available. The major virulence factor of STEC is Shiga toxin 2 (Stx2), which is encoded by the Stx2-converting bacteriophage 933 W used in this study, and phage induction plays a central role in toxin release and disease progression.In this study, we evaluated the protective in vivo effects of bismuth hydroxide gel (BHOG), a low-cost gastrointestinal compound with previously described antimicrobial and anti-toxin activities, in a murine model of STEC infection driven by the Stx2-converting bacteriophage 933 W. Mice treated with BHOG showed significantly higher survival rates compared than untreated controls (P = 0.0115), together with preservation of renal function, evidenced by significantly lower blood urea nitrogen and plasma urea levels (P < 0.05). Histological analysis demonstrated significantly reduced intestinal and renal tissues damage in treated animals compared with untreated controls. Overall, our findings provide in vivo evidence supporting a protective effect of BHOG against Shiga toxin-mediated disease. This study suggests that bismuth-based compounds may represent a potential adjunct to, or an alternative strategy for, the management of STEC-associated disease.
2026-08-11 | Influenza A(H1N1) triggered atypical hemolytic uremic syndrome in a child with homozygous CD46 variant successfully treated with ravulizumab: a case report.
To describe a pediatric case of aHUS triggered by influenza A(H1N1) infection in a patient with a homozygous pathogenic variant in CD46, successfully treated with ravulizumab. A previously healthy 12-year-old girl presented with a four-day history of fever, diarrhea, abdominal pain, mucosal bleeding, jaundice, and acute kidney injury. Initial evaluation confirmed microangiopathic hemolytic anemia and thrombocytopenia. ADAMTS13 activity was preserved. Nasopharyngeal polymerase chain reaction testing detected influenza A virus subtype H1N1, and a multiplex gastrointestinal polymerase chain reaction panel identified enteropathogenic Escherichia coli; Shiga toxin was not detected. Despite therapeutic plasma exchange and hemodialysis, there was no hematologic or renal improvement, and multi-organ involvement persisted, including respiratory failure and elevated pancreatic enzyme levels. Terminal complement inhibition with ravulizumab was initiated, leading to rapid hematologic normalization and full renal recovery by day 106. Genetic testing revealed a homozygous splice-site variant in CD46 (c.286 + 1G > C), consistent with atypical hemolytic uremic syndrome. This case underscores the importance of early C5 inhibition in complement-mediated thrombotic microangiopathy associated with defects in membrane-bound complement regulators, in which therapeutic plasma exchange may have limited efficacy. It also highlights how infections can act as triggers that unmask underlying genetic susceptibility.
2026-08-08 | Data-augmented machine learning refines the effective-concentration estimate for eculizumab in complement-mediated diseases.
Eculizumab, a humanized monoclonal antibody targeting the complement protein C5, is highly efficient in paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. However, recent reports have highlighted a subset of patients who show inadequate treatment response, prompting dose escalation or interval shortening. The serum concentration required for sustained inhibition of the complement lytic pathway remains uncertain, and the commonly cited 50-100 µg/ml range is not grounded in robust pharmacokinetic-pharmacodynamic data. Using publicly available clinical data digitized from four rare indications, we trained machine-learning supervised classifiers to predict complete C5 inhibition as a function of serum eculizumab concentration, identifying logistic regression on log-transformed concentration as the best and mechanistically appropriate model on real data. We then examined whether augmenting the real training data with high-fidelity synthetic data improves the resulting estimate. Although augmentation did not significantly change balanced accuracy, it reduced the confidence interval for the effective concentration by roughly 12-fold (a 92% reduction). The augmentation-stabilized estimate of the concentration associated with complete C5 inhibition was approximately 310.8-335.2 µg/ml (real-data-only estimate 338 µg/ml, 95% CI 275-454). These data-driven, hypothesis-generating results indicate that current maintenance targets aimed at near-complete C5 suppression may be substantially underestimated and that faithful synthetic augmentation can improve the precision of model-based pharmacological estimates in rare diseases; prospective validation in independent cohorts is required before any clinical application.
2026-08-06 | Shiga toxins and hemolytic uremic syndrome: pathogenesis, diagnosis, and therapy
Hemolytic Uremic Syndrome (HUS) is a severe thrombotic microangiopathy characterized by non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The most common form is caused by infections with Shiga toxin-producing Escherichia coli (STEC), which release potent Shiga toxins (Stx). This research addresses three objectives: elucidating mechanisms by which Stx subtypes contribute to HUS pathogenesis, developing a diagnostic platform for Stx detection, and evaluating novel therapeutic strategies. Patients infected with STEC co-producing Stx1 and Stx2 exhibit milder clinical manifestations than those infected with Stx2-producing strains. To investigate this, human blood was exposed to toxins, and extracellular vesicles (EV) were isolated and characterized. Co-exposure to both toxins produced a less toxic EV population, showing reduced number, size, and toxic cargo compared to EV generated by Stx2 alone, which are most strongly associated with HUS. Prompt STEC diagnosis is crucial for preventing HUS. A gold plasmonic biosensor was developed, coupling surface-enhanced Raman spectroscopy (SERS) with principal component analysis (PCA) for rapid Stx detection. The system recognizes Stx1a, Stx2a, and Stx2a-cleaved, enabling real-time analysis. Currently, no specific HUS therapy exists. NAB815, a polymyxin B derivative, emerged as a promising candidate. Previous studies showed sub-bactericidal NAB815 doses reduce Stx2a-containing EV formation in human blood. In vivo evaluation using CD1 mice demonstrated effective protection against kidney damage when NAB815 was co-administered with either free Stx2a or blood-derived Stx2a containing EV. Since antibiotics can trigger bacterial SOS response and increase Stx production, NAB815's safety was evaluated in both engineered and wildtype STEC strains. Results confirmed NAB815 as a safe strategy for HUS prevention and management. These findings provide new insights into HUS pathogenesis while offering innovative approaches for early diagnosis and targeted intervention in STEC infections.
2026-08-13 | Sirolimus application in patients with autoimmune-associated kidney diseases based on mTORC1 activation: a preliminary exploration and future perspectives.
The mTORC1 pathway drives pathogenesis in autoimmune kidney diseases. We hypothesized that intrarenal mTORC1 activation could identify patients likely to benefit from sirolimus, irrespective of their specific diagnosis. In this prospective proof-of-concept series, we screened eight patients with active autoimmune kidney disease for mTORC1 activation by immunohistochemistry on renal biopsy. Five positive patients (staining intensity: + to +++) received sirolimus, presenting with lupus nephritis atypical hemolytic uremic syndrome (aHUS), thrombotic microangiopathy (TMA), or IgA nephropathy (IgAN) associated with lung cancer. Over a mean follow-up of 25 months, four patients exhibited improved or stable renal function. All responders demonstrated moderate-to-high (++ to +++) mTORC1 staining, whereas the single non-responder who progressed to end-stage renal disease had only weak (+) staining. Proteinuria declined to <1 g/day in most responders. Sirolimus was well-tolerated. In two patients with concurrent malignancy, sirolimus did not aggravate stable breast cancer but was discontinued due to lung adenocarcinoma progression. This study indicates that intrarenal mTORC1 activation levels may help identify patients more likely to respond to sirolimus across various autoimmune kidney diseases, warranting further investigation as a precision-medicine approach.
2026-08-12 | Protective effects of bismuth hydroxide against hemolytic uremic syndrome caused by Shiga toxin producing Escherichia coli.
Shiga toxin-producing Escherichia coli (STEC) is a major cause of foodborne disease and hemolytic uremic syndrome (HUS), a severe condition for which no specific therapies are currently available. The major virulence factor of STEC is Shiga toxin 2 (Stx2), which is encoded by the Stx2-converting bacteriophage 933 W used in this study, and phage induction plays a central role in toxin release and disease progression.In this study, we evaluated the protective in vivo effects of bismuth hydroxide gel (BHOG), a low-cost gastrointestinal compound with previously described antimicrobial and anti-toxin activities, in a murine model of STEC infection driven by the Stx2-converting bacteriophage 933 W. Mice treated with BHOG showed significantly higher survival rates compared than untreated controls (P = 0.0115), together with preservation of renal function, evidenced by significantly lower blood urea nitrogen and plasma urea levels (P < 0.05). Histological analysis demonstrated significantly reduced intestinal and renal tissues damage in treated animals compared with untreated controls. Overall, our findings provide in vivo evidence supporting a protective effect of BHOG against Shiga toxin-mediated disease. This study suggests that bismuth-based compounds may represent a potential adjunct to, or an alternative strategy for, the management of STEC-associated disease.
2026-08-11 | Influenza A(H1N1) triggered atypical hemolytic uremic syndrome in a child with homozygous CD46 variant successfully treated with ravulizumab: a case report.
To describe a pediatric case of aHUS triggered by influenza A(H1N1) infection in a patient with a homozygous pathogenic variant in CD46, successfully treated with ravulizumab. A previously healthy 12-year-old girl presented with a four-day history of fever, diarrhea, abdominal pain, mucosal bleeding, jaundice, and acute kidney injury. Initial evaluation confirmed microangiopathic hemolytic anemia and thrombocytopenia. ADAMTS13 activity was preserved. Nasopharyngeal polymerase chain reaction testing detected influenza A virus subtype H1N1, and a multiplex gastrointestinal polymerase chain reaction panel identified enteropathogenic Escherichia coli; Shiga toxin was not detected. Despite therapeutic plasma exchange and hemodialysis, there was no hematologic or renal improvement, and multi-organ involvement persisted, including respiratory failure and elevated pancreatic enzyme levels. Terminal complement inhibition with ravulizumab was initiated, leading to rapid hematologic normalization and full renal recovery by day 106. Genetic testing revealed a homozygous splice-site variant in CD46 (c.286 + 1G > C), consistent with atypical hemolytic uremic syndrome. This case underscores the importance of early C5 inhibition in complement-mediated thrombotic microangiopathy associated with defects in membrane-bound complement regulators, in which therapeutic plasma exchange may have limited efficacy. It also highlights how infections can act as triggers that unmask underlying genetic susceptibility.
2026-08-08 | Data-augmented machine learning refines the effective-concentration estimate for eculizumab in complement-mediated diseases.
Eculizumab, a humanized monoclonal antibody targeting the complement protein C5, is highly efficient in paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. However, recent reports have highlighted a subset of patients who show inadequate treatment response, prompting dose escalation or interval shortening. The serum concentration required for sustained inhibition of the complement lytic pathway remains uncertain, and the commonly cited 50-100 µg/ml range is not grounded in robust pharmacokinetic-pharmacodynamic data. Using publicly available clinical data digitized from four rare indications, we trained machine-learning supervised classifiers to predict complete C5 inhibition as a function of serum eculizumab concentration, identifying logistic regression on log-transformed concentration as the best and mechanistically appropriate model on real data. We then examined whether augmenting the real training data with high-fidelity synthetic data improves the resulting estimate. Although augmentation did not significantly change balanced accuracy, it reduced the confidence interval for the effective concentration by roughly 12-fold (a 92% reduction). The augmentation-stabilized estimate of the concentration associated with complete C5 inhibition was approximately 310.8-335.2 µg/ml (real-data-only estimate 338 µg/ml, 95% CI 275-454). These data-driven, hypothesis-generating results indicate that current maintenance targets aimed at near-complete C5 suppression may be substantially underestimated and that faithful synthetic augmentation can improve the precision of model-based pharmacological estimates in rare diseases; prospective validation in independent cohorts is required before any clinical application.
2026-08-06 | Shiga toxins and hemolytic uremic syndrome: pathogenesis, diagnosis, and therapy
Hemolytic Uremic Syndrome (HUS) is a severe thrombotic microangiopathy characterized by non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The most common form is caused by infections with Shiga toxin-producing Escherichia coli (STEC), which release potent Shiga toxins (Stx). This research addresses three objectives: elucidating mechanisms by which Stx subtypes contribute to HUS pathogenesis, developing a diagnostic platform for Stx detection, and evaluating novel therapeutic strategies. Patients infected with STEC co-producing Stx1 and Stx2 exhibit milder clinical manifestations than those infected with Stx2-producing strains. To investigate this, human blood was exposed to toxins, and extracellular vesicles (EV) were isolated and characterized. Co-exposure to both toxins produced a less toxic EV population, showing reduced number, size, and toxic cargo compared to EV generated by Stx2 alone, which are most strongly associated with HUS. Prompt STEC diagnosis is crucial for preventing HUS. A gold plasmonic biosensor was developed, coupling surface-enhanced Raman spectroscopy (SERS) with principal component analysis (PCA) for rapid Stx detection. The system recognizes Stx1a, Stx2a, and Stx2a-cleaved, enabling real-time analysis. Currently, no specific HUS therapy exists. NAB815, a polymyxin B derivative, emerged as a promising candidate. Previous studies showed sub-bactericidal NAB815 doses reduce Stx2a-containing EV formation in human blood. In vivo evaluation using CD1 mice demonstrated effective protection against kidney damage when NAB815 was co-administered with either free Stx2a or blood-derived Stx2a containing EV. Since antibiotics can trigger bacterial SOS response and increase Stx production, NAB815's safety was evaluated in both engineered and wildtype STEC strains. Results confirmed NAB815 as a safe strategy for HUS prevention and management. These findings provide new insights into HUS pathogenesis while offering innovative approaches for early diagnosis and targeted intervention in STEC infections.
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Drug Discovery Landscape
2 orphan drug designations for Hemolytic uremic syndrome.
2 orphan drug designations for Hemolytic uremic syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Protein-based delivery vector carrying a DNA payload encoding an RNA-guided nuclease that targets stx genes of Shiga toxin-producing Escherichia coli | gene editing enzymes | EMA | 2020-08-21 | — | Eligo Bioscience |
Equine immunoglobulin F(ab')2 fragments targeting Shiga toxin | antibodies | EMA | 2018-05-25 | — | Chemo Research S.L. |
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