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Abstract: TH-OR067

Bevacizumab Associated Glomerulopathy: An Occlusive Hyaline Microangiopathy

Session Information

Category: Pathology and Lab Medicine

  • 1502 Pathology and Lab Medicine: Clinical

Authors

  • Wiech, Thorsten, Department of Pathology, University Hospital Hamburg Eppendorf, Hamburg, Germany
  • Person, Fermin J. K., UKE , Hamburg, Germany
  • Rinschen, Markus M., CECAD, Cologne, Germany
  • Brix, Silke R., University Hospital Hamburg-Eppendorf, Hamburg, Germany
  • Wulf, Sonia, Department of Pathology, University Hospital Hamburg Eppendorf, Hamburg, Germany
  • Noriega, Maria de las Mercedes, Department of Pathology, University Hospital Hamburg Eppendorf, Hamburg, Germany
  • Schmitz, Jessica, Hannover Medical School, Hannover, Germany
  • Schwarz, Anke, Hannover Medical School, Hannover, Germany
  • Ivanyi, Philipp, Hannover medical school, Hannover, Germany
  • Steinmetz, Oliver M., III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany
  • Reinhard, Linda, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany
  • Hoxha, Elion, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany
  • Zipfel, Peter F., Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
  • Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, Germany
Background

Bevacizumab is a humanized monoclonal IgG1 antibody which neutralizes vascular endothelial growth factor (VEGF) and is used for treating multiple cancer types. As a known and frequent adverse event, it can lead to renal damage including proteinuria and nephrotic syndrome.

Methods

In a retrospective approach we analyzed 16 renal biopsies from patients receiving bevacizumab treatment. We observed a distinctive pseudothrombotic pattern different from the previously reported thrombotic microangiopathy (TMA). Since the newly described pattern includes some features similar to TMA and cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), biopsies with these diagnoses were included for comparison. Clinical, laboratory, light microscopic, immunohistochemical (including a proximity ligation assay (PLA)), proteomic and electron microscopic features were assessed in 16 proteinuric patients after bevacizumab therapy and compared to seven cases of cryoglobulinemic MPGN and six cases of typical acute TMA.

Results

Nephrotic syndrome was present in 14 of the 16 bevacizumab-treated patients. All 16 displayed a patchy pattern of variably PAS-positive hyaline pseudothrombi occluding markedly dilated glomerular capillaries in their biopsies. Mass spectrometry based proteome analysis revealed a special protein pattern demonstrating some features of TMA and some of MPGN, including a strong accumulation of IgG in the thrombi. PLA did not show interaction of IgG with C1q, arguing for accumulation without classical complement activation. Compared to thrombi in TMA cases, the hyaline pseudothrombi did not contain clusters of CD61-positive thrombocytes. Electron microscopy of bevacizumab cases did not show extensive loss of podocyte foot processes.

Conclusion

Bevacizumab therapy can lead to a unique hyaline occlusive glomerulopathy, likely arising from endothelial leakage followed by subendothelial accumulation of serum proteins. Bevacizumab associated glomerulopathy can be diagnosed by light microscopy and is an important differential diagnosis in cancer patients with nephrotic syndrome.

Funding

  • Government Support - Non-U.S.