Acute Tubular Injury Confirmed by Overexpression of Stem/Progenitor Cell Marker CD133 is the Dominant Cause of Renal Failure in Several Variants of Drug-Induced Nephrotoxicity

Document Type

Conference Proceeding

Publication Date

9-2020

Publication Title

Archives of Pathology and Laboratory Medicine

Abstract

Context: Drug-induced nephrotoxicity has become an overwhelming issue for patients treated for metastatic tumors or other diseases. Although many variants of renal injury are present, acute tubular injury (ATI) appears to be the dominant form of injury. This study investigated whether CD133, a stem cell marker previously used to identify ATI, can be correlated to decreased renal function in nephrotoxicity caused by a variety of medications. Design: Seventeen control (unremarkable parenchyma from biopsy or nephrectomy for tumors) and 20 cases with nephrotoxicity were selected. The nephrotoxicities were secondary to a variety of nephrotoxic agents. The CD133 staining intensity was scored from 0 to 3þ, and percent of affected tubules in the cortex was noted. A combined score (intensity 3 percent of distribution) was calculated. Results: Cases with nephrotoxicity all stained positively with CD133, confirming ATI. Intensity (R ¼ 0.508, P ¼ .02), percent distribution (R ¼ 0.512, P ¼ .21), and combined score (R ¼ 0.547, P ¼ .01) were all positively correlated with serum creatinine. CD133 stained negatively in the proximal tubules of all controls. Overall area under the receiver operating characteristic curve was 0.95, indicating high specificity and sensitivity of CD133 for detecting acute tubular injury (Figure 148). Conclusions: Despite multiple variants of pathologic entities found in the nephrotoxicity cases, the degree of ATI confirmed by positive CD133 is positively correlated with presenting serum creatinine, implying that the acute injury in the proximal tubules is a significant contributor of renal failure during nephrotoxic insults.

Volume

144

Issue

9S1

First Page

e97

Comments

College of American Pathologists Annual Meeting, October 10-14, 2020, Virtual

Last Page

e97

DOI

10.5858/arpa.2020-0991-AB

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