Serial Non-Invasive Assessment of Antibody Induced Nephritis in Mice Using Positron Emission Tomography

Guiyang Hao,Yong Du,Xiankai Sun,Jianfei Guo,Xin J Zhou,Chandra Mohan,Orhan K Öz,Lbachir Benmohamed

doi:10.1371/journal.pone.0057418

Abstract

Mouse models of experimental anti-glomerular basement membrane (anti-GBM) nephritis provide an analytical tool for studying spontaneous lupus nephritis. The potential of Positron Emission Tomography (PET) was evaluated using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) as a probe to monitor the progression of anti-GBM induced nephritis in a mouse model. The imaging results were compared to conventional measures of renal function and pathological changes. Serum and urinary vascular cell adhesion molecule-1 (VCAM-1) levels were used as measures of endothelial cell activation and inflammation. Following a challenge with anti-glomerular antibodies, mice exhibited peak changes in serum creatinine, proteinuria, and glomerulonephritis score at 14 days post-challenge (p.c.). In contrast, VCAM levels peaked at day 7 p.c. On dynamic PET images (0–60 min) of day 7, kidneys of the anti-GBM nephritis mice demonstrated a unique pattern of FDG uptake. Compared to the time activity curve (TAC) prior to challenge, a rightward shift was observed after the challenge. By day 10 p.c., kidney FDG uptake was lower than baseline and remained so until the study ended at 21 days p.c. During this time frame measures of renal dysfunction remained high but VCAM-1 levels declined. These changes were accompanied by an increase in kidney volume as measured by Computed Tomography (CT) and intra-abdominal fluid collection. Our results suggest that FDG-PET-CT can be used as a non-invasive imaging tool to longitudinally monitor the progression of renal disease activity in antibody mediated nephritis and the magnitude of renal FDG retention correlates better with early markers of renal inflammation than renal dysfunction.

Highlights

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease
In order to clarify the pathological changes in the diseased animals, three to five mice in the anti-GBM nephritis group were sacrificed on days 0, 7, 10, 14, and 21
Currently, the gold standard for diagnosis and the treatment follow up of patients with lupus nephritis is histologic evaluation of invasive biopsies, which often results in patient morbidity, especially when multiple biopsies are performed

Summary

Introduction

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease. The Lupus Foundation of America estimates that 1.5 million Americans have lupus and at least 5 million worldwide. Renal involvement (lupus nephritis) is the foremost cause of morbidity and mortality in SLE patients [2]. Renal biopsy remains the gold standard to diagnose and assess the disease status of lupus nephritis patients. Due to inherent limitations of potential sampling errors and its invasive nature, multiple biopsies that are necessary for the assessment of the disease or treatment efficacy are undesirable and not routinely clinically performed. Clinically silent chronic changes of glomerulosclerosis and interstitial fibrosis secondary to chronic inflammation may go undetected with biopsy. These changes predispose to chronic kidney disease and end-stage renal disease. It would be of clinical value to develop a non-invasive method to detect or assess renal disease

Methods

Results

Conclusion