Diagnosis and treatment of complement-mediated thrombotic microangiopathies - consensus of the Genetic Diseases Committee of the Chilean Society of Nephrology

Sep 30, 2026

Uploaded by Mary Man

Thrombotic microangiopathy (TMA) is defined by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction, commonly involving the kidneys. Etiologies range from genetic disorders affecting complement proteins and other pathways to infections, autoimmune disease, malignancy, transplantation, pregnancy, and drugs, with markedly different treatment and outcomes. This consensus provides a structured approach for evaluating complement-mediated TMA (C-TMA), including when persistent TMA features after excluding secondary causes suggest C-TMA.

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Musalem etal. BMC Nephrology (2026) 27:21 [https://doi.org/10.1186/s12882-025-04739-3](https://doi.org/10.1186/s12882-025-04739-3) BMC Nephrology REVIEW Open Access Diagnosis and treatment of complementmediated thrombotic microangiopathies: consensus of the Genetic Diseases Committee of the Chilean Society of Nephrology Pilar Musalem1, Nicole Bascur2,3, Rodrigo A. Sepúlveda4, Paola Krall5, Andrea Lazcano6,7, Gustavo Navarro8,9, Angélica Rojo10,11* and Jean Grandy12,13* Abstract 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. *Correspondence: Angélica Rojo [arojo@calvomackenna.cl](arojo@calvomackenna.cl)[ ](arojo@calvomackenna.cl)Jean Grandy [antoinedufrance@yahoo.com](antoinedufrance@yahoo.com) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [

FAQs

What is complement-mediated thrombotic microangiopathy (C-TMA) and when should it be considered?

C-TMA is a subtype of TMA where features persist after resolution or exclusion of secondary causes. It should be considered when standard secondary etiologies are ruled out and TMA manifestations continue.

How is C-TMA diagnosis confirmed in the consensus?

Diagnosis relies on clinical judgment, histopathology, and a favorable response to C5 complement inhibitors such as eculizumab or ravulizumab. The treatment response is considered both diagnostic and prognostic.

Does the absence of complement gene variants rule out C-TMA?

No. Complement gene variants and copy number variations are found in up to 50–60% of patients, but their absence does not exclude C-TMA. Early complement inhibition is still recommended when appropriate.

Sep 30, 2026

Uploaded by Mary Man