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Review
. 2015 Oct;8(5):632-6.
doi: 10.1093/ckj/sfv059. Epub 2015 Jul 16.

Thrombotic microangiopathy associated with proteasome inhibitors

Ahad Lodhi  1 , Abhishek Kumar  1 , Muhammad U Saqlain  1 , Manish Suneja  1
Affiliations
Review

Thrombotic microangiopathy associated with proteasome inhibitors

Ahad Lodhi et al. Clin Kidney J. 2015 Oct.

Abstract

The ubiquitin proteasome pathway plays a key role in cell cycle, function and survival. Bortezomib (BTZ) and Carfilzomib (CFZ) are the first two inhibitors of the proteasome pathway, indicated in treatment of patients with multiple myeloma. In the past few years, there have been few case reports that have highlighted the association between proteasome inhibitors (BTZ and CFZ) with acute kidney injury (AKI). In most of these case reports and initial trials, the underlying mechanism of AKI has been unclear. In this article, we discuss the association and pathogenesis of proteasome inhibitors-associated AKI. We also report the first case of CFZ-associated AKI with kidney biopsy evidence of thrombotic microangiopathy and the presence of microangiopathic hemolytic anemia.

Keywords: onconephrology.

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Figures

Fig. 1.
Fig. 1.
Features of ongoing TMA under treatment. TMA-type changes. These changes were very focal in the biopsy, and most arteries and glomeruli were essentially unremarkable or showed nonspecific ‘ischemia/recovery’ changes. (A) Focal small interlobular artery/pre-arterioles: luminal narrowing with pale mucoid edema (arrow), and endothelial cell reaction, with erythrocyte fragmentation and ‘entrapment’ (arrowheads) within the intimal layer, which shows myointimal widening and clearing of cytoplasm in the myocyte cell layer (H&E stain 40× magnifications). Adjacent renal tubules show features of acute tubular injury. The inset figure shows a trichrome stain (60× magnification), which enhances the fragmented erythrocytes (the hallmark finding of microvascular hemolysis) in red and a pale intima with no significant collagen deposition (which would have stained blue). (B) Glomerulus: capillary loop ‘double-contours’ [arrow, sharp silver positive (black) linear staining on each of the capillary loop sides, which does not stain in between them], which indicate glomerular basement membranes reduplication response to endothelial damage (note the ‘plump’ endothelial cell occlusion, asterisk). Also noted is ischemic wrinkling (‘collapse’—arrowhead) of other glomerular capillary loops (Jones methenamine silver stain, 60× magnification). BC (Bowman's capsule).
Fig. 2.
Fig. 2.
Proposed pathogenesis of proteasome inhibitor-associated thrombotic microangiopathy.
See this image and copyright information in PMC

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