非典型溶血性尿毒症症候群

Both atypical hemolytic uremic syndrome (aHUS) and malignant hypertension (MHT) are causes of thrombotic microangiopathy (TMA), and their coexistence has been reported. We describe a 22-year-old man who exhibited severe hypertension, pulmonary hemorrhage, and acute kidney injury. Laboratory evaluation revealed thrombocytopenia, microangiopathic hemolytic anemia, and severe kidney dysfunction, without evidence of retinal hemorrhage or renal artery stenosis. Given suspicion for MHT-related thrombotic microangiopathy or immune-mediated pulmonary-renal syndrome, antihypertensive therapy, continuous hemodiafiltration, corticosteroids, and plasma exchange were initiated. However, autoimmune serologic testing was negative, von Willebrand factor protease (ADAMTS13) activity was preserved without inhibitor, and stool cultures were negative, leading to discontinuation of plasma exchange and tapering of corticosteroids. Thereafter, hematologic abnormalities transiently improved, but kidney dysfunction persisted, and pulmonary hemorrhage and cytopenia recurred with a marked reduction in complement C3 despite stabilized blood pressure reduction. Plasma exchange was resumed, and ravulizumab was initiated. Kidney biopsy demonstrated ischemic glomerular changes without immune deposits and marked narrowing of the interlobar arteries. Although genetic analysis identified variants in complement-related genes, definitive causative abnormalities remained undetermined. The patient was discharged with recovered kidney function, normalization of complement proteins, and sustained hematologic remission. Collectively, this clinical course is compatible with aHUS. We consider that MHT might trigger overt aHUS with pulmonary-renal syndrome-like features.

RATIONALE: Systemic lupus erythematosus (SLE)-associated thrombotic microangiopathy with features of atypical hemolytic uremic syndrome (aHUS) is a rare but life-threatening complication. Early recognition is challenging because of its overlapping clinical manifestations with other thrombotic microangiopathies. PATIENT CONCERNS: A 49-year-old man with SLE presented with anemia, thrombocytopenia, and multi-system involvement. Despite initial immunosuppressive therapy, his hematologic parameters progressively deteriorated, with hemoglobin decreasing to 89 g/L and the platelet count to 54 × 109/L. DIAGNOSES: Laboratory investigations demonstrated elevated lactate dehydrogenase (501 U/L) and markedly increased soluble complement membrane attack complex (sC5b-9, >1790 ng/mL). ADAMTS13 activity was normal (75.41%), excluding thrombotic thrombocytopenic purpura. Based on the clinical and laboratory findings, the patient was diagnosed with SLE-associated aHUS. INTERVENTIONS: Following the diagnosis, the patient received eculizumab, a monoclonal antibody targeting complement component C5. OUTCOMES: Within 6 days of eculizumab treatment, hemoglobin increased to 102 g/L, and the platelet count recovered to 108 × 109/L, indicating a rapid hematologic response. LESSONS: This case highlights that aHUS can occur as a severe complication of SLE, even in male patients. Complement-mediated thrombotic microangiopathy may coexist with and be triggered by immune hemolysis in SLE. Early recognition and prompt complement inhibition with eculizumab can produce an ultra-rapid hematologic response and may be critical for improving patient outcomes.

Thrombotic microangiopathy (TMA) is a histopathological entity characterized by endothelial injury and microvascular thrombosis, clinically presenting with microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction. TMA encompasses a heterogeneous group of disorders with overlapping clinical features, challenging consistent classification. Traditional designations such as typical hemolytic uremic syndrome (HUS), atypical HUS (aHUS), primary TMA and secondary TMA have often blurred the underlying mechanisms they were meant to distinguish. In recent years, complement-mediated TMA has garnered attention, largely because complement inhibition represents the only effective targeted therapy currently available. This therapeutic success has inadvertently led to a strong emphasis on complement activity in other TMAs, where complement activation is frequently detected but not necessarily causal and pivotal. This review focuses on non-complement mediated TMA, in particular those associated with coagulation dysregulation, VEGF deficiency, and direct endothelial injury. In these entities, complement activation typically represents a downstream consequence rather than the initiating event. Understanding the distinct molecular pathways underlying these forms is essential for accurate disease classification and rational therapeutic targeting.

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.