C5 Inhibition for Anti-Cancer Therapy-Induced Renal Thrombotic Microangiopathy

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ID: 333319
2026
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Abstract
Abstract Background and Hypothesis Thrombotic microangiopathy (TMA) is increasingly recognized as a complication of both cancer and anti-cancer therapies. C5 complement inhibition is used in selected cases, but evidence supporting its effectiveness, particularly in kidney biopsy-proven disease, remains limited. Methods This retrospective cohort study included adult patients with biopsy-proven TMA attributed to anti-cancer therapies between 2015 and 2026 at Mayo Clinic, USA. Patients were stratified according to treatment with complement inhibition versus no complement inhibition therapy. The primary outcome was renal recovery; secondary outcomes included hematological recovery, composite outcome, overall survival, and longitudinal changes in hematologic and renal function parameters. Results A total of 31 patients with kidney biopsy-proven TMA related to anti-cancer therapy were included. Nine received complement inhibition, and 22 did not. A higher proportion of patients in the treated group achieved complete or partial renal recovery at 3 months (p = 0.008), hematologic recovery at 1 month (p = 0.007) and composite outcome (complete-partial renal plus hematologic recovery) (p = 0.041). During follow-up, platelet counts increased significantly at 1 month and 3 months (p = 0.045, both) in the treated group. Mixed-effects modeling showed significantly lower longitudinal estimated glomerular filtration rate (eGFR) values in the untreated group (β = −13.9 mL/min per 1.73 m², p = 0.028). In the gemcitabine-associated TMA subgroup, complete-partial renal recovery occurred only in treated patients (p = 0.021) and hematologic recovery was achieved in the whole cohort but occurred significantly faster in the complement inhibition group (p = 0.019). The higher rate of renal recovery persisted in sensitivity analysis (p = 0.021). Conclusions In this rigorously phenotyped cohort of patients with biopsy-proven, anti-cancer therapy-associated renal TMA, we observed a signal of benefit from C5 inhibition, most consistently for renal recovery and possibly extending to hematologic outcomes, particularly among patients with gemcitabine-associated TMA.
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Authors Michele Barbarini, Coraima Claudia Nava Chavez, Pouneh Mirkheshti, Charat Thongprayoon, Ronald S. Go, Meera R. Sridharan, Loren Paola Herrera Hernandez, Nelson Leung, Sandra M. Herrmann
Journal nephrology dialysis transplantation
Year 2026
DOI
10.1093/ndt/gfag246
URL
https://doi.org/10.1093/ndt/gfag246
Keywords Keywords not found

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