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Worsening membranous nephropathy in a patient with GIST treated with sunitinib
Shahrzad Zonoozi1, Matthew Palmer2, Teitelbaum Ursina3
1Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Abstract:
Tyrosine kinase inhibitors (TKI) are anticancer agents widely used for a variety of malignancies including gastrointestinal stromal tumours (GIST). Although generally well-tolerated, TKIs have been associated with a number of adverse events including hypertension, proteinuria and nephrotic syndrome. We present the case of a 70-year-old patient with metastatic GIST on long-standing sunitinib who developed hypertension, oedema and hypoalbuminemia with a rising serum creatinine and was found to have nephrotic syndrome. Workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titres and a kidney biopsy confirmed PLA2R-positive membranous nephropathy without findings of thrombotic microangiopathy. Cessation of sunitinib led to reduction in anti-PLA2R antibody IgG titres while resumption, due to concern for cancer progression, led to worsening symptoms. Treatment with rituximab led to undetectable anti-PLA2R IgG titres. We highlight the importance of maintaining a systematic approach for evaluating nephrotic syndrome and provide a case showing that TKIs can exacerbate underlying nephrotic syndrome.
Insights
Tyrosine kinase inhibitors (TKIs) can worsen underlying nephrotic syndrome, as seen in a patient with gastrointestinal stromal tumors. Discontinuation and rituximab treatment improved kidney function and reduced associated antibodies.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) are crucial anticancer agents for malignancies like gastrointestinal stromal tumors (GIST).
- While effective, TKIs can cause adverse renal events, including hypertension, proteinuria, and nephrotic syndrome.
- A systematic approach is vital for diagnosing nephrotic syndrome in patients on TKI therapy.
Observation:
- A 70-year-old patient with metastatic GIST on sunitinib developed nephrotic syndrome, characterized by hypertension, edema, hypoalbuminemia, and rising creatinine.
- Diagnostic workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titers.
- Kidney biopsy confirmed PLA2R-positive membranous nephropathy without thrombotic microangiopathy.
Findings:
- Sunitinib cessation correlated with reduced anti-PLA2R antibody IgG titers.
- Resuming sunitinib due to cancer progression led to symptom exacerbation.
- Rituximab treatment resulted in undetectable anti-PLA2R IgG titers, indicating successful management.
Implications:
- This case underscores the potential for TKIs to exacerbate pre-existing nephrotic syndrome.
- Highlights the importance of vigilant renal monitoring in patients receiving TKI therapy.
- Suggests rituximab as a potential therapeutic option for TKI-induced or exacerbated PLA2R-associated membranous nephropathy.
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