Renal Contrast-Enhanced Sonography Findings in a Model of Acute Cellular Allograft Rejection

Abstract

These authors contributed equally to this study.Noninvasive methods to diagnose and differentiate acute cellular rejection from acute tubular necrosis or acute calcineurin inhibitor toxicity are still missing. Because T lymphocytes play a decisive role in early states of rejection, we investigated the suitability and feasibility of antibody-mediated contrastenhanced ultrasound by using microbubbles targeted to CD3 + , CD4+ , or CD8 + T cells in different models of renal disease. In an established rat renal transplantation model, CD3-mediated ultrasound allows the detection of acute rejection as early as on postoperative day 2. Ultrasound signal intensities increased with the severity of inflammation. Further, an early response to therapy could be monitored by using contrast-enhanced sonography. Notably, acute tubular necrosis occurring after ischemia-reperfusion injury as well as acute calcineurin inhibitor toxicity could easily be differentiated. Finally, the quantified ultrasound signal correlated significantly with the number of infiltrating T cells obtained by histology and with CD3 mRNA levels, as well as with chemokine CXCL9, CXCL11, and CCL19 mRNA but not with KIM-1 mRNA expression, thereby representing the severity of graft inflammation but not the degree of kidney injury. In summary, we demonstrate that antibody-mediated contrast-enhanced ultrasound targeting T lymphocytes could be a promising tool for an easy and reproducible assessment of acute rejection after renal transplantation.

Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients. Part I.In vivoimaging methods

“…Grabner et al [30] recently performed a study using antibody-mediated contrast-enhanced US (CEUS) using microbubbles targeting CD3-, CD4- or CD8-positive T-cells in various murine models of kidney diseases. The results of CEUS correlated with histopathological scoring of rejection, CD3 immuno-signal and mRNA expression levels of chemoattractant cytokines.…”

“…Thus, CD3-mediated CEUS may help specifically detect renal AR. Further preclinical and clinical studies are warranted to assess the diagnostic yield of CEUS in real-life settings since infection-induced infiltration of T-lymphocytes may represent an important confounding factor [30]. …”

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation

“…There are a number of studies that used microbubbles with targeted ligands for adhesion molecules that accumulate at the sites of injury (46)(47)(48)(49). However, the expression of these molecules could change due to a number of variables, including the type and potency of immunosuppressive agents used in different transplant cohorts.…”

Recent advances in renal imaging

“…A strong signal was seen four hours after the induction of ischemia/reperfusion using both probes. Microbubbles targeted to other molecules have also been used to detect renal inflammation, including the detection of T cells in a model of allograft rejection 59 , and activated neutrophils in a model of ischemic AKI 60 . These methods may be useful for detecting markers of allograft rejection that currently require a tissue biopsy to identify them.…”