Pegylated-liposomal Doxorubicin-induced Glomerular Thrombotic Microangiopathy

Abstract

Pegylated liposomal doxorubicin (PLD) has emerged as a recent innovation within the realm of antineoplastic agents, distinguished by its incorporation of doxorubicin within the liposomal bilayer. Given the low risk of cardiotoxicity, the clinical use of PLD has been expanding. We encountered a patient who underwent extended PLD therapy for recurrent malignancy and subsequently developed PLD-associated thrombotic microangiopathy, which was diagnosed by a detailed pathophysiological assessment. This case underscores the importance of considering thrombotic microangiopathy as a potential differential diagnosis in patients presenting with unexplained hypertension and renal impairment during prolonged PLD monotherapy.

Keywords: drug induced kidney injury; liposome; ovarian cancer; polyethylene glycol (PEG); proteinuria.

Figure 1.

Contrast-enhanced computed tomography findings. A mass lesion with heterogeneous contrast enhancement and a cystic lesion were observed on the right side of the pelvis (red arrowhead). A mass lesion was also observed in the right lung and right lobe of the liver (yellow arrowhead).

Figure 2.

Clinical course. GFR: glomerular filtration rate, Cr: creatinine

Figure 3.

Kidney biopsy findings. a: Segmental mesangiolysis and solidification of the glomerular tuft with pale stained hyaline-like material (red arrowheads) (Periodic acid-Schiff stain, original magnification ×200). b: Expansion of subendothelial spaces and double contours in the glomerular capillary walls (blue arrowheads) (Periodic acid-methenamine silver stain, original magnification ×200). c: Hyalinosis in some arterioles (yellow arrowheads) (Periodic acid-methenamine silver stain, original magnification ×200). d: Segmental deposition of fibrinogen in the glomerular capillaries (direct immunofluorescence for fibrinogen, original magnification ×200).

Figure 4.

Electron microscopic findings in the glomerulus. a: Severe mesangiolysis with leakage of red blood cells in edematous expanded subendothelial spaces (original magnification ×1,200). b: Severe edematous expanded subendothelial spaces (original magnification ×2,500). c: Fine droplet-like deposits in the subendothelial spaces of some glomerular tufts (original magnification ×6,000).

Figure 5.

Serial sections of the glomerulus with Periodic acid-Schiff stain (a), immunostaining for CD31 (b) and CD68 (c). a: Glomerulus with segmental hyalinosis and capsular adhesion (Periodic acid-Schiff stain, original magnification ×200). b: Segmentally attenuated CD31 staining in the glomerulus with mesangial expansion (red arrowheads) (immunoenzyme staining for CD31; original magnification, ×200). c: Few CD68-positive cells are observed (only one, yellow arrowhead) (immunoenzyme staining for CD68; original magnification, ×200).