Multiparametric magnetic resonance imaging of experimental chronic kidney disease: A quantitative correlation study with histology.

Karin Jandeleit-Dahm,Gunnar Schley,Tobias Bäuerle,Stephan Ellmann,Carsten Willam,Kai-Uwe Eckardt,Michael Uder,Jutta Jordan,Seymour Rosen

doi:10.1371/journal.pone.0200259

Abstract

ObjectivesIn human chronic kidney disease (CKD) the extent of renal tubulointerstitial fibrosis correlates with progressive loss of renal function. However, fibrosis can so far only be assessed by histology of kidney biopsies. Magnetic resonance imaging (MRI) can provide information about tissue architecture, but its potential to assess fibrosis and inflammation in diseased kidneys remains poorly defined.Materials and methodsWe evaluated excised kidneys in a murine adenine-induced nephropathy model for CKD by MRI and correlated quantitative MRI parameters (T1, T2, and T2* relaxation times, apparent diffusion coefficient and fractional anisotropy) with histological hallmarks of progressive CKD, including renal fibrosis, inflammation, and microvascular rarefaction. Furthermore, we analyzed the effects of paraformaldehyde fixation on MRI parameters by comparing kidney samples before and after fixation with paraformaldehyde.ResultsIn diseased kidneys T2 and T2* relaxation times, apparent diffusion coefficient and fractional anisotropy in the renal cortex and/or outer medulla were significantly different from those in control kidneys. In particular, T2 relaxation time was the best parameter to distinguish control and CKD groups and correlated very well with the extent of fibrosis, inflammatory infiltrates, tubular dilation, crystal deposition, and loss of peritubular capillaries and normal tubules in the renal cortex and outer medulla. Fixation with paraformaldehyde had no impact on T2 relaxation time and fractional anisotropy, whereas T1 times significantly decreased and T2* times and apparent diffusion coefficients increased in fixed kidney tissue.ConclusionsMRI parameters provide a promising approach to quantitatively assess renal fibrosis and inflammation in CKD. Especially T2 relaxation time correlates well with histological features of CKD and is not influenced by paraformaldehyde fixation of kidney samples. Thus, T2 relaxation time might be a candidate parameter for non-invasive assessment of renal fibrosis in human patients.

Highlights

Chronic kidney disease (CKD) is considered a major health problem affecting approximately 14% of the general adult population in the United States [1]
We evaluated excised kidneys in a murine adenine-induced nephropathy model for CKD by magnetic resonance imaging (MRI) and correlated quantitative MRI parameters (T1, T2, and T2* relaxation times, apparent diffusion coefficient and fractional anisotropy) with histological hallmarks of progressive CKD, including renal fibrosis, inflammation, and microvascular rarefaction
Fixation with paraformaldehyde had no impact on T2 relaxation time and fractional anisotropy, whereas T1 times significantly decreased and T2* times and apparent diffusion coefficients increased in fixed kidney tissue

Summary

Introduction

Chronic kidney disease (CKD) is considered a major health problem affecting approximately 14% of the general adult population in the United States [1] It is associated with high morbidity, all-cause and cardiovascular mortality, and health care expenditures [2]. CKD can progress to end-stage renal disease requiring dialysis or kidney transplantation [3] It is defined as the presence of persistent (>3 months) structural or functional kidney abnormalities (detected by urinalysis, imaging studies, or histology) with or without decreased glomerular filtration rate (GFR) (

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