Diagnostic yield of 18F-FDG PET/CT imaging and urinary CXCL9/creatinine levels in kidney allograft subclinical rejection

Abstract

Subclinical kidney allograft acute rejection (SCR) corresponds to “the unexpected histological evidence of acute rejection in a stable patient.” SCR detection relies on surveillance biopsy. Noninvasive approaches may help avoid biopsy‐associated complications. From November 2015 to January 2018, we prospectively performed positron emission tomography/computed tomography (PET/CT) after injection of F18‐fluorodeoxyglucose (18F‐FDG) in adult kidney transplant recipients with surveillance biopsy at ~3 months posttransplantation. The Banff‐2017 classification was used. The ratio of the mean standard uptake value (mSUVR) between kidney cortex and psoas muscle was measured. Urinary levels of CXCL‐9 were concomitantly quantified. Our 92‐patient cohort was categorized upon histology: normal (n = 70), borderline (n = 16), and SCR (n = 6). No clinical or biological difference was observed between groups. The mSUVR reached 1.87 ± 0.55, 1.94 ± 0.35, and 2.41 ± 0.54 in normal, borderline, and SCR groups, respectively. A significant difference in mSUVR was found among groups. Furthermore, mSUVR was significantly higher in the SCR vs normal group. The area under the receiver operating characteristic curve (AUC) was 0.79, with 83% sensitivity using an mSUVR threshold of 2.4. The AUC of urinary CXCL‐9/creatinine ratios comparatively reached 0.79. The mSUVR positively correlated with ti and acute composite Banff scores. 18F‐FDG‐PET/CT helps noninvasively exclude SCR, with a negative predictive value of 98%. External validations are required.

An Antibody-Aptamer-Hybrid Lateral Flow Assay for Detection of CXCL9 in Antibody-Mediated Rejection after Kidney Transplantation

“…Compared to serum creatinine, CXCL9 indicates graft rejection earlier and more sensitively [ 3 , 51 , 59 ]. We could show that CXCL9 is highly elevated in urine of KTRs with AMR, which is in line with results of others [ 54 ]. Of note, the CXCL9 mean level was higher in AMR than in TCMR urine samples and CXCL9 was not significantly increased in serum and urine of TCMR patients of the cohorts reported here.…”

“…CXCL9 has previously been shown to have diagnostic potential as urine biomarker within TCMR [ 52 , 53 , 54 , 55 , 56 , 57 ] and BK virus nephropathy together with CXCL10 [ 58 ]. Compared to serum creatinine, CXCL9 indicates graft rejection earlier and more sensitively [ 3 , 51 , 59 ].…”

Observer variability in the assessment of renal 18F-FDG uptake in kidney transplant recipients

“…This rapid imaging technique does not cause any side-effect in patients with renal failure from normal to mildly reduced GFR to end-stage renal disease. Furthermore, we have recently showed that 18 F-FDG PET/CT may help rule out subclinical rejection in stable KTR, with a negative predictive value of 98% 23 . Our results support conclusions of previous studies which showed that the uptake of 18 F-FDG by kidneys in non-transplant patients and in KTR is not influenced by renal function 24,25 , and that the alteration of GFR does not significantly compromise the clearance of background activity 26 .…”

Basic principles and new advances in kidney imaging

“…Metabolism. PET-derived uptake of [18F]fluorodeoxyglucose (FDG) is a powerful index of kidney metabolism, 50 and 2-tert-butyl-4-chloro-5-[6-(4-[( 18) F]fluorobutoxy)pyridin-3-ylmethoxy]-2H-pyridazin-3-one ( 18 F-BCPP-BF) uptake detects mitochondrial function in vivo, 27 but both are limited by radioactivity and low spatial resolution. Hyperpolarized-carbon-13 MRI is an emerging technique based on enzymatic conversion of injected hyperpolarized substrates, which provides both chemical and spatial information.…”