Browsing by Author "Rojo, Angélica"

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    Diagnosis and treatment of complement-mediated thrombotic microangiopathies: consensus of the Genetic Diseases Committee of the Chilean Society of Nephrology
    (2026) Musalem, Pilar; Bascur, Nicole; Sepúlveda Palamara, Rodrigo Andrés; Krall, Paola; Lazcano, Andrea; Navarro, Gustavo; Rojo, Angélica; Grandy, Jean
    Thrombotic microangiopathy (TMA) is a clinical-pathological syndrome defined by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction, commonly affecting the kidneys. The etiologies are diverse and include genetic disorders (affecting complement proteins or other pathways, such as cobalamin metabolism), infections, autoimmune diseases, malignancies, transplantation, pregnancy, and drugs. Differentiating these causes is essential, as treatment strategies and prognoses vary widely. This consensus document, developed by a multidisciplinary group of clinicians and geneticists, provides a structured approach for evaluating TMA, with particular focus on complement-mediated TMA (C-TMA). C-TMA should be considered when TMA features persist after resolution or exclusion of secondary causes. Diagnostic confirmation relies on clinical judgment, histopathology, and a favorable response to C5 complement inhibitors, such as eculizumab or ravulizumab. This therapeutic response is considered both diagnostic and prognostic. Complement gene variants (e.g., CFH, CFI, MCP/CD46, and others) and copy number variations (e.g., CFHR1-5 deletions) are found in up to 50–60% of patients, but their absence does not rule out C-TMA. Early complement inhibition may prevent irreversible organ damage and should not be delayed by pending genetic results. Genetic counseling is advised for all patients, regardless of variant status, to assess familial risk and guide long-term follow-up. A consensus aims to outline scenarios in which treatment initiation is strongly recommended, including severe or relapsing disease, chronic kidney dysfunction, among others. In Chile and Latin America, TMA remains underdiagnosed due to limited access to specialized diagnostic tools and delays in recognizing clinical subtypes. The availability of molecular testing and complement studies is restricted, often delaying targeted therapies. Treatment still relies heavily on plasma exchange, with limited access to complement inhibitors. This consensus aims to standardize care, improve early recognition, and support rational use of targeted therapies in C-TMA, particularly in regions with limited access to specialized testing or complement inhibitors.