Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination Microscopy Using Elastica-Masson- and Periodic-Acid-Schiff-Stained Kidney Sections

Overview

Journal Kidney Int Rep

Publisher Elsevier

Specialty Nephrology

Date 2021 Jul 26

PMID 34307987

Citations 5

Authors

Ayumi Matsumoto

Isao Matsui

Yusuke Katsuma

Seiichi Yasuda

Karin Shimada

Tomoko Namba-Hamano

Yusuke Sakaguchi

Jun-Ya Kaimori

Yoshitsugu Takabatake

Kazunori Inoue

Yoshitaka Isaka

Affiliations

Soon will be listed here.

Abstract

Introduction: Foot process effacement and mitochondrial fission associate with kidney disease pathogenesis. Electron microscopy is the gold-standard method for their visualization, but the observable area of electron microscopy is smaller than light microscopy. It is important to develop alternative ways to quantitatively evaluate these microstructural changes because the lesion site of renal diseases can be focal.

Methods: We analyzed elastica-Masson trichrome (EMT) and periodic acid-Schiff (PAS) stained kidney sections using structured illumination microscopy (SIM).

Results: EMT staining revealed three-dimensional (3D) structures of foot process, whereas ponceau xylidine acid fuchsin azophloxine solution induced fluorescence. Conversion of foot process images into their constituent frequencies by Fourier transform showed that the concentric square of (1/4)-(1/16) in the power spectra (PS) included information for normal periodic structures of foot processes. Foot process integrity, assessed by PS, negatively correlated with proteinuria. EMT-stained sections revealed fragmented mitochondria in mice with mitochondrial injuries and patients with tubulointerstitial nephritis; Fourier transform quantified associated mitochondrial injury. Quantified mitochondrial damage in patients with immunoglobulin A (IgA) nephropathy predicted a decline in estimated glomerular filtration rate (eGFR) after kidney biopsy but did not correlate with eGFR at biopsy. PAS-stained sections, excited by a 640 nm laser, combined with the coefficient of variation values, quantified subtle changes in the basement membranes of patients with membranous nephropathy stage I.

Conclusions: Kidney microstructures are quantified from sections prepared in clinical practice using SIM.

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