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

Abstract

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ultimately relies on transplant needle biopsy. However, such an invasive procedure is associated with a significant risk of complications and is limited by sampling error and interobserver variability. In the present review, we summarize the current literature about non-invasive approaches for the diagnosis of AR in kidney transplant recipients (KTRs), including in vivo imaging, gene expression profiling and omics analyses of blood and urine samples. Most imaging techniques, like contrast-enhanced ultrasound and magnetic resonance, exploit the fact that blood flow is significantly lowered in case of AR-induced inflammation. In addition, AR-associated recruitment of activated leukocytes may be detectable by ¹⁸F-fluoro-deoxy-glucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, IP-10 and 18S RNA levels, have been identified. None of these approaches has been adopted yet in the clinical follow-up of KTRs, but standardization of procedures may help assess reproducibility and compare diagnostic yields in large prospective multicentric trials.

Keywords: 18FDG-PET/CT; acute rejection; kidney biopsy; kidney transplantation; magnetic resonance imaging; ultrasonography.

Fig. 1.

Representative Doppler ultrasound imaging in case of biopsy-proven renal allograft acute rejection. Doppler ultrasound images of a renal allograft (from the same kidney transplant recipient) (A) without versus (B) with biopsy-proven acute rejection (AR). The index of resistance (IR; normal value <0.70) of renal parenchyma is significantly increased in the case of AR (B). VSM, maximal systolic velocity; VTD, telediastolic velocity.

Fig. 2.

Representative ¹⁸F-FDG PET/CT imaging in case of biopsy-proven renal allograft acute rejection. Positron-emission tomography (PET; left column), computed tomography (CT; middle column) and combined PET/CT images taken ∼180 min after intravenous administration of ¹⁸fluoro-deoxy-glucose (¹⁸FDG) are shown for one kidney transplant recipient (KTR) with normal renal histology (upper panels) and one KTR with biopsy-proven acute rejection (AR). The tracer, ¹⁸FDG, significantly accumulates in the renal parenchyma in case of AR. Note the detection of excreted ¹⁸FDG in the urinary pelvis in both normal and pathological situations. The arbitrary scale of the standard uptake value (from 0 to 5) is illustrated on the right side.