Acute Tubular Injury (ATI) Secondary to Thrombotic Microangiopathy Can Be Morphologically Different From Primary ATI Due to Ischemia

Document Type

Conference Proceeding

Publication Date

3-2018

Publication Title

Laboratory Investigation

Abstract

Background: ATI can occur in all three segments of proximal tubules (PT); S1 occurs mainly in convoluted PT, S2 mainly in medullary rays, and S3 at cortico-medullary junctions. In-vivo experimental investigations and our human biopsy studies all demonstrate that S2 and S3, likely due to their low oxygen supplies, are more vulnerable to ischemic injury compared to the S1 segment of PT. The goal of this study was to investigate whether ATI secondary to thrombotic microangiopathy (TMA) was morphologically different from ATI due to ischemic/toxic injury (primary ATI, so called acute tubular necrosis [ATN]). Design: Seventeen (17) TMA cases with dominant glomerular involvement and 18 primary ATN cases were stained for a specific injury marker of PT, kidney injury molecule-1 (monoclonal anti-KIM-1 antibody AKG7), whereas some were also stained for the injury markers CD133 and CD68 by immunohistochemical method. The expression of both KIM-1 and CD133 in S1 vs S2/S3 (S3 was often absent in core biopsies) were recorded as either: 0 (no staining), +/- (focal weak staining), 1+ (entire luminal weak staining), 2+ (entire luminal moderate staining), or 3+ (entire luminal strong staining). Cytoplasmic granular staining of CD68 was also graded from 0 to 3+. Twelve (12) cases without kidney injury were also stained with all three markers as negative controls. Results: Negative controls without kidney injury (n=12) all stained negative for the three markers. In 17 TMA cases, 15 of 17 cases (88%) show higher or similar S1 staining for the injury markers when compared to S2/S3 segments of PT. By contrast, only 8 out of 8 primary ATN cases (44%) revealed higher or similar S1 staining for the injury markers when compared to S2/S3 segments, whereas the remaining 56% of cases with primary ATN demonstrated dominant injury staining in S2/S3 segments of PT. Conclusions: Our data indicate that TMA often results in ATI, which mainly affected the S1 segment of PT around the thrombotic glomeruli, as well as some of the S2 segment, a feature which helps us support a diagnosis of TMA when no definite thrombi are present. Primary ATN, often due to overall renal ischemia, can affect all segments from S1 to S2/S3, with more injury seen in the S2/S3 segments, which are supplied by low oxygen blood and thus more vulnerable to further ischemic insults.

Volume

98

Issue

Suppl 1

First Page

607

Comments

United States and Canadian Academy of Pathology (USCAP) 107th Annual Meeting, March 17-23, 2018, Vancouver, BC, Canada

Last Page

607

DOI

10.1038/labinvest.2018.16

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