Journal article
Mitotic Catastrophe Causes Podocyte Loss in the Urine of Human Diabetics
The American journal of pathology, Vol.189(2), pp.248-257
02/2019
DOI: 10.1016/j.ajpath.2018.10.016
PMCID: PMC6943371
PMID: 30472210
Abstract
Mitotic catastrophe (MC) is a major cause of podocyte loss in vitro and in vivo. We evaluated urine samples (n = 184 urine samples from diabetic patients; n = 41 patients) from diabetic patients and determined the presence of podocytes in the urine and studied their characteristics, specifically asking whether apoptosis versus MC is present. We also evaluated diabetic glomeruli in renal biopsy specimens by electron microscopy (n = 54). A battery of stains including the antibody to podocalyxin (PCX) were used. PCX and podocytes (PCX+podo) showed nuclear morphologies such as a i) mononucleated normal shape (8.7%), ii) large and abnormal shape (3.8%), iii) multinucleated with or without micronucleoli (31.2%), iv) mitotic spindles (8.2%), v) single nucleus and denucleation combined (10.3%), and vi) denucleation only (37.0%). Large size/abnormal shape, multinucleation, mitotic spindles, and a combination of single nucleus and denucleation were considered features of MC (53.5%). Dual staining of PCX+podo was positive for Glepp 1 (50%), whereas none of PCX+podo were positive for nephrin, podocin, leukocyte, or parietal epithelial cell markers (cytokeratin 8), annexin V, cleaved caspase-3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Ten percent of PCX+podo were positive for phosphorylated vimentin. Electron microscopy identified cellular and nuclear podocyte changes characteristic of MC. The majority of urine podocytes in diabetic patients showed MC, not apoptosis. This noninvasive approach may be clinically useful in determining progressive diabetic nephropathy or response to therapeutic intervention.
Details
- Title: Subtitle
- Mitotic Catastrophe Causes Podocyte Loss in the Urine of Human Diabetics
- Creators
- Masanori Hara - Iwamuro Health Promotion Center, Niigata, Japan. Electronic address: mhara@iwamurohp.jpKazuhiko Oohara - Department of Medicine, Yoshida Hospital, Niigata, JapanDao-Fu Dai - Department of Pathology, University of Iowa, Iowa City, IowaHelen Liapis - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; Renal Pathology, Arkana Laboratories, Little Rock, Arkansas. Electronic address: helen.liapis@arkanalabs.com
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.189(2), pp.248-257
- Publisher
- United States
- DOI
- 10.1016/j.ajpath.2018.10.016
- PMID
- 30472210
- PMCID
- PMC6943371
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Grant note
- K08 HL145138 / NHLBI NIH HHS
- Language
- English
- Date published
- 02/2019
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984047888502771
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