Sunitinib-induced endocapillary proliferative glomerulonephritis with IgA2 deposit in addition to thrombotic microangiopathy: a case report

BMC Nephrol. 2024 Aug 30;25(1):284. doi: 10.1186/s12882-024-03732-6.

Abstract

Background: Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used as a second-line therapy for gastrointestinal stromal tumors (GIST) resistant to imatinib. However, its impact on the vascular endothelial growth factor (VEGF) pathway can lead to significant toxicities, including hypertension and thrombotic microangiopathy (TMA).

Case presentation: This case report describes a unique instance of a patient with metastatic GIST who developed endocapillary proliferative glomerulonephritis (EPGN) with IgA2 deposits and TMA following sunitinib treatment. The patient presented with severe hypertension, nephrotic syndrome, and acute kidney injury. Renal biopsy confirmed the diagnosis, revealing IgA2 deposits, which are not commonly associated with TMA. Discontinuation of sunitinib led to a rapid improvement in renal function and proteinuria. The potential mechanisms underlying sunitinib-induced glomerular injury may involve the blockade of VEGFR-1, affecting immune cell recruitment and function, and the disruption of the nitric oxide and endothelin systems, leading to endothelial damage and immune dysregulation. Management of these toxicities requires a personalized approach, with options ranging from symptomatic relief to drug discontinuation. The use of endothelin receptor antagonists and other therapeutic alternatives for GIST management is discussed.

Conclusions: This case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.

Keywords: Case report; IgA2 deposit; Sunitinib; Thrombotic microangiopathy; Vascular endothelial growth factor blockade.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / therapeutic use
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors* / drug therapy
  • Glomerulonephritis, IGA / pathology
  • Glomerulonephritis, Membranoproliferative / chemically induced
  • Glomerulonephritis, Membranoproliferative / drug therapy
  • Glomerulonephritis, Membranoproliferative / pathology
  • Humans
  • Immunoglobulin A / metabolism
  • Male
  • Middle Aged
  • Sunitinib* / adverse effects
  • Sunitinib* / therapeutic use
  • Thrombotic Microangiopathies* / chemically induced

Substances

  • Sunitinib
  • Antineoplastic Agents
  • Immunoglobulin A