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

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 (18 F-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. 18 F-FDG-PET/CT helps noninvasively exclude SCR, with a negative predictive value of 98%. External validations are required.

[18F-FDG positron emission tomography in non-oncological renal pathology: Current indications and perspectives]. / La tomographie par émission de positons au 18F-FDG en pathologie rénale non oncologique : indications actuelles et perspectives.

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological nephrology since conventional radiological approaches after injection of contrast agents are relatively contra-indicated in patients with chronic kidney disease (CKD). PET/CT after i.v. injection of 18F-fluoro-deoxy-glucose (FDG) is not toxic and is characterized by a high sensitivity. The level of irradiation (∼5mSv) is acceptable. CKD does not significantly influence tissue uptake of 18F-FDG. The purpose of the present review aims at detailing the non-oncological indications of 18F-FDG PET/CT in general nephrology and after kidney transplantation. Particularly, 18F-FDG PET/CT appears useful in the diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease, as well as in the characterization of retroperitoneal fibrosis. In kidney transplant recipients, 18F-FDG PET/CT may help in the diagnostic work-up of suspected acute rejection, thereby eventually avoiding unnecessary kidney transplant biopsy. Perspectives in 18F-FDG PET/CT imaging are discussed, including innovative approaches of image analysis.

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

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.

Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients, part II: omics analyses of urine and blood samples.

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the 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, such as 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 leucocytes may be detectable by 18F-fluorodeoxyglucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, CXCL10 and 18S RNA levels, have been identified. None of these approaches has yet been adopted in the clinical follow-up of KTRs, but standardization of analysis procedures may help assess reproducibility and comparative diagnostic yield in large, prospective, multicentre trials.

Two novel mutations of the CLDN16 gene cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy leads to urinary loss of Mg(2+) and Ca(2+), with subsequent nephrocalcinosis and end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient reached ESRD at 23 and benefited from kidney transplantation.