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
2,251 drug discovery papers related to Hemolytic uremic syndrome, with 4 first-in-class and 14 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2,251 drug discovery papers related to Hemolytic uremic syndrome, with 4 first-in-class and 14 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-09 | [Atypical hemolytic uremic syndrome: key points in differential diagnosis and recent advances in treatment].
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by endothelial injury resulting from dysregulated activation of the alternative complement pathway. Clinical outcomes have markedly improved since the anti-complement agent eculizumab, an anti-C5 monoclonal antibody, became available in 2013. However, no established diagnostic method directly assesses complement activation for definitive diagnosis. In practice, diagnosis relies on the evaluation of pathogenic variants in complement-related genes as predisposing factors and on the exclusion of other diseases that can cause TMA. Consequently, distinguishing aHUS from secondary TMA can sometimes be clinically challenging. In particular, secondary TMA associated with hypertensive emergencies or pregnancy may overlap with aHUS, requiring careful diagnostic consideration. In recent years, several novel anti-complement agents have been developed. In addition to therapies targeting the terminal complement pathway downstream of C5, agents that act on the proximal complement cascade are also under development, and further clinical evidence on these strategies is awaited.
2026-07-09 | Complement System Inhibitors in Nephrology: A Comprehensive Review.
Background. The complement system plays a critical role in the pathogenesis of several kidney diseases. Dysregulation of complement activation, particularly of the alternative pathway, leads to kidney injury via thrombotic microangiopathy, immune complex deposition, and direct podocyte damage. Summary. Complement system inhibitors represent a paradigm shift in nephrology therapeutics, offering targeted treatment for diseases previously associated with poor outcomes. This review comprehensively examines the present landscape of complement inhibition in kidney disease, including established therapies and emerging agents. Terminal complement inhibitors (eculizumab and ravulizumab) have revolutionized the treatment of atypical haemolytic uremic syndrome, demonstrating remarkable improvements in renal outcomes and survival. Proximal pathway inhibitors targeting Factor B (Iptacopan) and C3 (pegcetacoplan) show promise in C3 glomerulopathy and IgA nephropathy, with recent phase 3 trials demonstrating significant proteinuria reduction. Additional applications include immune complex membranoproliferative glomerulonephritis and ANCA-associated vasculitis, in which complement activation contributes to disease pathogenesis. However, these agents present unique challenges, including infection risk, particularly meningococcal disease, cost considerations, and uncertainty regarding optimal treatment duration.
2026-07-07 | A case report of atypical hemolytic uremic syndrome with a CFH mutation complicated by recurrent posterior reversible encephalopathy syndrome.
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction, particularly affecting the kidneys and the central nervous system. It is caused by genetic variants or autoantibodies involved in dysregulation of the complement system. Pathogenic variants of the complement factor H (CFH) gene are associated with severe disease and may lead to life-threatening multiorgan failure during the acute phase. We report a case of CFH mutation-positive aHUS complicated by recurrent posterior reversible encephalopathy syndrome (PRES) during the course of treatment. A 32-year-old woman presented with progressive fatigue and acute dyspnea. Laboratory tests revealed hemolytic anemia, thrombocytopenia, and severe acute kidney injury. A peripheral blood smear revealed schistocytes, consistent with TMA. On hospital day 1, she developed generalized tonic-clonic seizures followed by respiratory arrest that required mechanical ventilation. Continuous hemodialysis was initiated for severe renal failure. After the exclusion of thrombotic thrombocytopenic purpura, typical hemolytic uremic syndrome, and secondary causes of TMA, a clinical diagnosis of aHUS was made. Genetic testing later revealed a pathogenic heterozygous CFH variant (c.3572C>T, p.Ser1191Leu), confirming the diagnosis of aHUS. Anti-C5 monoclonal antibody (eculizumab) was initiated based on the clinical diagnosis of aHUS. Intensive care management, including mechanical ventilation, renal replacement therapy, plasma exchange, and strict blood pressure control, was also provided. During the course of the disease, she developed severe cardiomyopathy and recurrent PRES. Early initiation of complement inhibition combined with intensive care management resulted in complete neurological recovery, and the patient was discharged home without any sequelae. This case highlights that CFH mutation-positive aHUS can be complicated by severe multiorgan dysfunction, including cardiomyopathy and recurrent PRES. Early clinical recognition and prompt initiation of complement inhibition were central to the favorable outcome, while intensive blood pressure control and comprehensive supportive care may have contributed to neurological recovery.
2026-07-09 | [Atypical hemolytic uremic syndrome: key points in differential diagnosis and recent advances in treatment].
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by endothelial injury resulting from dysregulated activation of the alternative complement pathway. Clinical outcomes have markedly improved since the anti-complement agent eculizumab, an anti-C5 monoclonal antibody, became available in 2013. However, no established diagnostic method directly assesses complement activation for definitive diagnosis. In practice, diagnosis relies on the evaluation of pathogenic variants in complement-related genes as predisposing factors and on the exclusion of other diseases that can cause TMA. Consequently, distinguishing aHUS from secondary TMA can sometimes be clinically challenging. In particular, secondary TMA associated with hypertensive emergencies or pregnancy may overlap with aHUS, requiring careful diagnostic consideration. In recent years, several novel anti-complement agents have been developed. In addition to therapies targeting the terminal complement pathway downstream of C5, agents that act on the proximal complement cascade are also under development, and further clinical evidence on these strategies is awaited.
2026-07-09 | Complement System Inhibitors in Nephrology: A Comprehensive Review.
Background. The complement system plays a critical role in the pathogenesis of several kidney diseases. Dysregulation of complement activation, particularly of the alternative pathway, leads to kidney injury via thrombotic microangiopathy, immune complex deposition, and direct podocyte damage. Summary. Complement system inhibitors represent a paradigm shift in nephrology therapeutics, offering targeted treatment for diseases previously associated with poor outcomes. This review comprehensively examines the present landscape of complement inhibition in kidney disease, including established therapies and emerging agents. Terminal complement inhibitors (eculizumab and ravulizumab) have revolutionized the treatment of atypical haemolytic uremic syndrome, demonstrating remarkable improvements in renal outcomes and survival. Proximal pathway inhibitors targeting Factor B (Iptacopan) and C3 (pegcetacoplan) show promise in C3 glomerulopathy and IgA nephropathy, with recent phase 3 trials demonstrating significant proteinuria reduction. Additional applications include immune complex membranoproliferative glomerulonephritis and ANCA-associated vasculitis, in which complement activation contributes to disease pathogenesis. However, these agents present unique challenges, including infection risk, particularly meningococcal disease, cost considerations, and uncertainty regarding optimal treatment duration.
2026-07-07 | A case report of atypical hemolytic uremic syndrome with a CFH mutation complicated by recurrent posterior reversible encephalopathy syndrome.
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction, particularly affecting the kidneys and the central nervous system. It is caused by genetic variants or autoantibodies involved in dysregulation of the complement system. Pathogenic variants of the complement factor H (CFH) gene are associated with severe disease and may lead to life-threatening multiorgan failure during the acute phase. We report a case of CFH mutation-positive aHUS complicated by recurrent posterior reversible encephalopathy syndrome (PRES) during the course of treatment. A 32-year-old woman presented with progressive fatigue and acute dyspnea. Laboratory tests revealed hemolytic anemia, thrombocytopenia, and severe acute kidney injury. A peripheral blood smear revealed schistocytes, consistent with TMA. On hospital day 1, she developed generalized tonic-clonic seizures followed by respiratory arrest that required mechanical ventilation. Continuous hemodialysis was initiated for severe renal failure. After the exclusion of thrombotic thrombocytopenic purpura, typical hemolytic uremic syndrome, and secondary causes of TMA, a clinical diagnosis of aHUS was made. Genetic testing later revealed a pathogenic heterozygous CFH variant (c.3572C>T, p.Ser1191Leu), confirming the diagnosis of aHUS. Anti-C5 monoclonal antibody (eculizumab) was initiated based on the clinical diagnosis of aHUS. Intensive care management, including mechanical ventilation, renal replacement therapy, plasma exchange, and strict blood pressure control, was also provided. During the course of the disease, she developed severe cardiomyopathy and recurrent PRES. Early initiation of complement inhibition combined with intensive care management resulted in complete neurological recovery, and the patient was discharged home without any sequelae. This case highlights that CFH mutation-positive aHUS can be complicated by severe multiorgan dysfunction, including cardiomyopathy and recurrent PRES. Early clinical recognition and prompt initiation of complement inhibition were central to the favorable outcome, while intensive blood pressure control and comprehensive supportive care may have contributed to neurological recovery.
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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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