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Pegylated Liposomal Doxorubicin Causes Kidney-limited Thrombotic Microangiopathy
Ilya Glezerman1, Steven Salvatore2, William Tap3
1Renal Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
Abstract:
A definite causal link between pegylated liposomal doxorubicin (PLD) and kidney-limited thrombotic microangiopathy (TMA) remains unestablished. Here, we report 2 cases of PLD-induced kidney-limited TMA, 1 in a patient with myxofibrosarcoma and the other in a patient with liposarcoma. The 2 patients received a high cumulative dose of PLD, and both presented with a rise in serum creatinine and proteinuria. Kidney biopsy revealed TMA with chronic mesangiolysis and capillary wall double contouring. Neither patient had concomitant exposure to TMA-causing drugs, such as gemcitabine, anti-vascular endothelial growth factor agents, or mammalian target of rapamycin inhibitors. The work-up for secondary causes of TMA was negative in both patients. The cessation of PLD therapy led to improvement or stabilization in serum creatinine and proteinuria in both patients. These 2 cases provide a clear causal link between PLD and kidney-limited TMA. The high cumulative dose of PLD increases the risk of kidney TMA. Early recognition of PLD-induced kidney TMA can lead to timely cessation of PLD therapy and potentially preserve kidney function.
Insights
Pegylated liposomal doxorubicin (PLD) can cause kidney-limited thrombotic microangiopathy (TMA). High cumulative doses of PLD increase TMA risk, but stopping treatment may preserve kidney function.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- The causal link between pegylated liposomal doxorubicin (PLD) and kidney-limited thrombotic microangiopathy (TMA) has not been definitively established.
- Thrombotic microangiopathy (TMA) is a serious condition affecting small blood vessels, often leading to organ damage.
Observation:
- Two cases of kidney-limited TMA are presented in patients treated with PLD for myxofibrosarcoma and liposarcoma.
- Both patients received high cumulative doses of PLD and exhibited elevated serum creatinine and proteinuria.
- Kidney biopsies confirmed TMA with specific pathological features, and other causes of TMA were ruled out.
Findings:
- The study establishes a clear causal relationship between PLD and kidney-limited TMA.
- High cumulative doses of PLD were identified as a significant risk factor for developing kidney TMA.
- Cessation of PLD therapy resulted in improved or stabilized kidney function in both reported cases.
Implications:
- Early identification of PLD-induced kidney TMA is crucial for prompt treatment.
- Timely discontinuation of PLD therapy can potentially prevent irreversible kidney damage.
- These findings highlight the importance of monitoring renal function in patients receiving high-dose PLD.
