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Kidney Week

Abstract: SA-PO0206

Long-Term Kidney Outcomes in Gemcitabine-Bevacizumab-Induced Thrombotic Microangiopathy Treated with Complement Inhibition: A Case Series

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Shukla, Parnika, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Bertan, Sara H, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Kelly, Adam, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Gudsoorkar, Prakash Shashikant, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
  • Gupta, Shruti, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Hanna, Paul, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Background

Drug-induced thrombotic microangiopathy (DI-TMA) is a rare and potentially fatal adverse effect in patients with cancer receiving dual chemotherapy with gemcitabine and bevacizumab. Uncertainty of which agent led to TMA may trigger premature discontinuation of life-saving therapies; unfortunately, data on renal outcomes and therapeutic strategies are limited. In this case series, we evaluate the effect of terminal complement (C5) inhibition on renal recovery.

Methods

Leveraging the TriNetX Research Network, we identified adult cancer patients who received gemcitabine and bevacizumab within a 3-month interval, subsequently diagnosed with TMA (ICD-9/10 codes), and treated with C5 inhibitors (eculizumab or ravulizumab). Renal and hematologic parameters were assessed over 6 months post-treatment completion.

Results

Four patients with DI-TMA attributed to dual therapy were included (mean age 59.0 ± 8.5 years; 75% female). All had pre-existing hypertension and renal impairment at baseline (mean sCr 2.88 ± 1.55 mg/dL). Predominantly, patients had gynecologic cancer (75%). At TMA onset, the mean systolic and diastolic BPs were 154.5 ± 34.7 mmHg and 79.8 ± 18.7 mmHg, respectively. Laboratory findings revealed elevated LDH (533 IU/L) and thrombocytopenia (77.5 × 10^9/L) at time of TMA diagnosis. After C5 blockade, we observed improvements in renal function and hematologic markers (Fig. 1). The median [IQR] time from TMA diagnosis to C5 inhibitor therapy was 15.5 [7.0-43.5] days, with a median treatment duration of 23 [10.5-33.0] days. The median interval between discontinuing the offending agents and starting C5 inhibition was 19 [10.5-71.0] days.

Conclusion

C5 inhibition was associated with improved renal function and hematologic parameters in these patients, suggesting complement pathway involvement. However, the lack of a consistent trend in BP recovery proposes an alternate mechanism, such as endothelial dysfunction from VEGF inhibition.

Figure 1. Recovery trends

Digital Object Identifier (DOI)