Pegylated Liposomal Doxorubicin Causes Kidney-limited Thrombotic Microangiopathy

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.

Keywords: TMA, Pegylated doxorubicin, acute kidney injury.

Figure 1.

(A) Chronic thrombotic microangiopathy with mesangiolysis and capillary wall double contour formation (Jones stain; original magnification x600). (B) Endothelial injury with subendothelial widening and electron lucent material (electron microscopy; original magnification x 12000). (C) Chronic thrombotic microangiopathy with capillary wall multilayering and mesangiolysis (periodic acid–Schiff stain; original magnification, x400). (D) Endothelial injury with subendothelial widening, basement membrane duplication, and subendothelial ‘hyaline’ accumulation (electron microscopy; original magnification, x12000).