Acute Kidney Allograft Rejection Research Articles

#2894 pre-mRNA FOXP3 levels after transplant do not reflect risk of rejection

Abstract Background and Aims Forkhead box P3 (FOXP3) is the master gene regulator of T regulatory cells, and is crucial for their suppressive function. In kidney transplant recipients, low post-transplant levels of FOXP3 in peripheral blood has been associated with increased risk of kidney allograft rejection. However, it is unknown if low post-transplant levels of FOXP3 pre-mRNA is also associated with increased risk of kidney allograft rejection. Here we aim to test if pre-mRNA FOXP3 levels are associated with the risk of rejection post-transplant in kidney transplant recipients. Method We collected blood samples from incident kidney transplant recipients the first day after transplantation. From these, we extracted peripheral blood mononuclear cell ribonucleic acid and measured pre-mRNA FOXP3 transcripts with quantitative reverse transcription polymerase chain reaction. Pre-mRNA FOXP3 levels were normalized to β-actin, and converted to a logarithmic scale. We collected data concerning rejection episodes through medical record review. Kidney transplant recipients that had at least one recorded acute kidney allograft rejection episode within the first three months post-transplant were defined as recipients with a rejection episode. Data is presented as median [interquartile range] and tested with Wilcoxon rank sum test. Results We measured pre-mRNA FOXP3 in 515 incident kidney transplant recipients, 52 experienced a rejection episode within the first three months post-transplant. Pre-mRNA levels did not differ between recipients with vs without rejection, logarithmic value of normalized pre-mRNA FOXP3 −4.48 [−4.63 to −4.10] vs −4.41 [−4.69 to −4.11], p = 0.80. The pattern persisted regardless of donor type, deceased recipients with rejection (N = 25) vs deceased recipients without—(N = 268), −4.47 [−4.62 to −4.26] vs −4.46 [−4.71 to −4.25], p = 0.90. Living ABO-compatible recipients with rejection (N = 19) vs living ABO-compatible recipients without—(N = 139), −4.49 [−4.64 to −4.14] vs −4.35 [−4.65 to −3.93], p = 0.30. Living ABO-incompatible recipients with rejection (N = 8) vs living ABO-compatible recipients without—(N = 56), −4.13 [−4.48 vs −3.88] vs −4.20 [−4.61 to −3.88], p = 0.70. Conclusion In kidney transplant recipients, early post-transplant abundance of pre-mRNA FOXP3 transcripts were similar regardless of risk of kidney allograft rejection post-transplant.

The uptake of [18F]-fluorodeoxyglucose by the renal allograft correlates with the acute Banff scores of cortex inflammation but not with the 1-year graft outcomes.

[18F]FDG PET/CT noninvasively disproves acute kidney allograft rejection (AR) in kidney transplant recipients (KTRs) with suspected AR. However, the correlation of biopsy-based Banff vs. PET/CT-based scores of acute inflammation remains unknown, as does the prognostic performance of [18F]FDG PET/CT at one year post suspected AR. From 2012 to 2019, 114 [18F]FDG-PET/CTs were prospectively performed in 105 adult KTRs who underwent per cause transplant biopsies. Ordinal logistic regression assessed the correlation between the extent of histological inflammation and the mean standardized [18F]FDG uptake values (mSUVmean). Functional outcomes of kidney allografts were evaluated at one year post per cause biopsy and correlated to mSUVmean. A significant correlation between mSUVmean and acute Banff score was found, with an adjusted R 2 of 0.25. The mSUVmean was significantly different between subgroups of "total i", with 2.30 ± 0.71 in score 3 vs. 1.68 ± 0.24 in score 0. Neither the function nor the survival of the graft at one year was statistically related to mSUVmean. [18F]FDG-PET/CT may help noninvasively assess the severity of kidney allograft inflammation in KTRs with suspected AR, but it does not predict graft outcomes at one year.

#5189 THE ASSOCIATION BETWEEN CD86 +1057G>A POLYMORPHISM AND ACUTE KIDNEY ALLOGRAFT REJECTION AMONG EGYPTIAN PATIENTS

Abstract Background and Aims T-cell mediated immune response is crucial in kidney transplantation and plays an important role in allograft rejection. . CD86 is a costimulatory molecule that participates in the regulation of T-cell lymphocytes activation. Single nucleotide polymorphisms (SNPs) located in this gene have been studied with inconsistent results. The aim of the study was to examine the association between (rs1129055:G/A) polymorphism in the CD86 gene and the development of acute renal allograft rejection among Egyptian patients. Method In this non- concurrent cohort study, we included a group of 50 kidney transplant recipients diagnosed by acute allograft rejection (AR) (which was defined by clinical diagnosis, elevated serum creatinine >30% of basal line in the absence of other pathology including infection, urinary tract obstruction, allograft artery stenosis or calcineurin toxicity and responded to treatment by immunosuppression and was confirmed by positive biopsy that was graded according to BANFF classification) and another matched group of 50 kidney transplant recipients without AR and all of the 100 patients were genotyped by direct sequencing for CD 86 polymorphism (rs1129055:G/A) by TaqMan genotyping assay. Results The genotypic frequencies of CD 86 rs1129055 SNP in the acute rejection group were 72% GG, 28% AG and 0% AA while in the no rejection group it were 66% GG, 30% AG and 4% AA. The AA genotype and A allele at position +1057 in the CD86 gene were more frequent in patients without AR (4% and 23.4%, respectively) compared with those showing an AR (0% and 16.2%, respectively). The odds of acute rejection weren`t statistically significant either in dominant or recessive model (P = 0.665 and 0.475 respectively). Conclusion These results suggest that AA genotype and A allele of CD86 +1057G>A polymorphism may provide a nonsignificant protection against acute kidney allograft rejection among Egyptian patients.

Autoantibodies against DNA topoisomerase I promote renal allograft rejection by increasing alloreactive T cell responses

Antibodies reactive to self-antigens are an important component of posttransplant immune responses. The generation requirements and functions of autoantibodies, as well as the mechanisms of their influence on alloimmune responses, still remain to be determined. Our study investigated the contribution of autoimmunity during rejection of renal allografts. We have previously characterized a mouse model in which the acute rejection of a life-supporting kidney allograft is mediated by antibodies. At rejection, recipient sera screening against >4000 potential autoantigens revealed DNA topoisomerase I peptide 205-219 (TI-I205-219) as the most prominent epitope. Subsequent analysis showed TI-I205-219-reactive autoantibodies are induced in nonsensitized recipients of major histocompatibility complex–mismatched kidney allografts in a T cell–dependent manner. Immunization with TI-I205-219 broke self-tolerance, elicited TI-I205-219 immunoglobin G autoantibodies, and resulted in acute rejection of allogeneic but not syngeneic renal transplants. The graft loss was associated with increased priming of donor-reactive T cells but not with donor-specific alloantibodies elevation. Similarly, passive transfer of anti-TI-I205-219 sera following transplantation increased donor-reactive T cell activation with minimal effects on donor-specific alloantibody levels. The results identify DNA topoisomerase I as a novel self-antigen in transplant settings and demonstrate that autoantibodies enhance activation of donor-reactive T cells following renal transplantation.

Efficacy of Double Membrane Filtration Immunoadsorption in Severe C1q-Binding Donor-Specific Antibody-Positive Acute Humoral Kidney Allograft Rejection: A Case Series

Introduction: Acute antibody-mediated rejection (ABMR) is an important threat to renal allograft survival in the early transplant period and the major single cause of graft loss in the first postoperative year. Semi-selective immunoadsorption (IA) remains one of the commonly applied treatments in ABMR, reducing allo-reactive antibody load. Adding double filtration plasmapheresis (DFPP) to IA might enhance therapeutic efficacy by also addressing innate humoral effectors like complement factors. Methods: Four patients with ABMR were treated with DFPP + IA. Clinical, histological, and immunological data and adverse events were retrospectively collected. Results: Here we present four high-risk treatment-refractory ABMR cases with C1q-binding donor-specific antibodies and histology of humoral rejection under treatment with DFPP + IA. While the earlier cases (within the first year after transplantation) showed marked reduction in ABMR severity and improvement of kidney function, the later cases did not respond accordingly. Late ABMR patient 1 stabilized, whereas late ABMR patient 2 did not respond to treatment. Conclusions: Our data support the consideration of DFPP + IA as a rescue treatment option in early, severe, high-risk ABMR cases in which other treatments failed.

The Medawar Prize Acceptance Speech 2022.

The Medawar Prize Acceptance Speech 2022.

Acute antibody-mediated rejection of kidney allograft; mind the fibrin thrombi

Acute antibody-mediated rejection of kidney allograft; mind the fibrin thrombi

The Role of Complement Split-products as Biomarkers for Acute Antibody-mediated Rejection of Kidney Allografts.

Background.Acute antibody-mediated rejection (AMR) is mediated by the activation of the classical complement system in addition to noncomplement-dependent inflammatory pathways. Complement fixation by donor-specific antibodies leads to cleavage of the complement proteins C4, C3, and C5 to produce multiple complement split-products (CSP) and the end-effector membrane attack complex, C5b-9. In this study, we investigate CSP as potential biomarkers for AMR.Methods.In an Institutional Review Board–approved, prospective, controlled study, CSP levels were measured in blood and urine samples from consecutive kidney transplant recipients with biopsy-proven AMR (n = 10), acute cellular rejection (ACR) (n = 5), or no rejection (n = 5). After obtaining informed consent, samples were collected at the time of biopsy (day 0) and days 15 (end of rejection treatment) and 30 postbiopsy for AMR and ACR patients. ELISA was used to measure C5a, C4d, and soluble C5b-9 concentrations in blood and urine, in addition to factor Bb (Bb) concentration in blood only. Kidney transplant histopathology was evaluated using the Banff 2013 classification. Rejection treatment and follow-up were performed per standard of care.Results.Blood and urine CSP levels adjusted to urine creatinine were not elevated in AMR compared to no rejection and ACR arms. There was significant variability in CSP concentration within each of the study groups.Conclusion.Our study does not support the utility of CSP as surrogate biomarkers of AMR; however, it is limited by the small sample size and larger studies may be warranted.

Targeting inflammatory monocytes by immune-modifying nanoparticles prevents acute kidney allograft rejection

Inflammatory monocytes are a major component of the cellular infiltrate in acutely rejecting human kidney allografts. Since immune-modifying nanoparticles (IMPs) bind to circulating inflammatory monocytes via the specific scavenger receptor MARCO, causing diversion to the spleen and subsequent apoptosis, we investigated the therapeutic potential of negatively charged, 500-nm diameter polystyrene IMPs to prevent kidney allograft rejection. Kidney transplants were performed from BALB/c (H2d) to C57BL/6 (H2b) mice in two groups: controls (allo) and allo mice infused with IMPs. Groups were studied for 14 (acute rejection) or 100 (chronic rejection) days. Allo mice receiving IMPs exhibited superior survival and markedly less acute rejection, with better kidney function, less tubulitis, and diminished inflammatory cell density, cytokine and cytotoxic molecule expression in the allograft and lower titers of donor-specific IgG2c antibody in serum at day 14, as compared to allo mice. Cells isolated from kidneys from allo mice receiving IMPs showed reduced Ly6Chi monocytes, CD11b+ cells and NKT+ cells compared to allo mice. IMPs predominantly bound CD11b+ cells in the bloodstream and CD11b+ and CD11c-B220+ marginal zone B cells in the spleen. In the spleen, IMPs were found predominantly in red pulp, colocalized with MARCO and expression of cleaved caspase-3. At day 100, allo mice receiving IMPs exhibited reduced macrophage M1 responses but were not protected from chronic rejection. IMPs afforded significant protection from acute rejection, inhibiting both innate and adaptive alloimmunity. Thus, our current experimental findings, coupled with our earlier demonstration of IMP-induced protection in kidney ischemia-reperfusion injury, identify IMPs as a potential induction agent in kidney transplantation.

Acute Kidney Allograft Rejection Following Coronavirus mRNA Vaccination: A Case Report.

Supplemental Digital Content is available in the text.

Successful treatment of acute kidney allograft rejection using extracorporeal photopheresis in the context of post‐transplant lymphoproliferative diseases: three successive cases

We reported 3 kidney transplant patients with PTLD who developed mixed AR following IS treatment minimization. AR episodes were treated with extracorporeal photopheresis (ECP), methylprednisolone and IVIG. In all patients, graft function improved under ECP and stabilized in the long term. These observations suggest that ECP is safe and efficient for treatment of AR in the context of PTLD.

Circular RNAs in kidney disease and cancer.

Circular RNAs (circRNAs) are a class of endogenously expressed regulatory RNAs with a single-stranded circular structure. They are generated by back splicing and their expression can be tightly regulated by RNA binding proteins. Cytoplasmic circRNAs can function as molecular sponges that inhibit microRNA-target interactions and protein function or as templates for the efficient generation of peptides via rolling circle amplification. They can also act as molecular scaffolds that enhance the reaction kinetics of enzyme-substrate interactions. In the nucleus, circRNAs might facilitate chromatin modifications and promote gene expression. CircRNAs are resistant to degradation and can be packaged in extracellular vesicles and transported in the circulation. Initial studies suggest that circRNAs have roles in kidney disease and associated cardiovascular complications. They have been implicated in hypertensive nephropathy, diabetic kidney disease, glomerular disease, acute kidney injury and kidney allograft rejection, as well as in microvascular and macrovascular complications of chronic kidney disease, including atherosclerotic vascular disease. In addition, several circRNAs have been reported to have oncogenic or tumour suppressor roles or to regulate drug resistance in kidney cancer. The available data suggest that circRNAs could be promising diagnostic and/or prognostic biomarkers and potential therapeutic targets for kidney disease, cardiovascular disease and kidney cancer.

Recipient myeloperoxidase-producing cells regulate antibody-mediated acute versus chronic kidney allograft rejection.

Antibody-mediated rejection (ABMR) continues to be a major problem undermining the success of kidney transplantation. Acute ABMR of kidney grafts is characterized by neutrophil and monocyte margination in the tubular capillaries and by graft transcripts indicating NK cell activation, but the myeloid cell mechanisms required for acute ABMR have remained unclear. Dysregulated donor-specific antibody (DSA) responses with high antibody titers are induced in B6.CCR5–/– mice transplanted with complete MHC-mismatched A/J kidneys and are required for rejection of the grafts. This study tested the role of recipient myeloid cell production of myeloperoxidase (MPO) in the cellular and molecular components of acute ABMR. Despite induction of equivalent DSA titers, B6.CCR5–/– recipients rejected A/J kidneys between days 18 and 25, with acute ABMR, whereas B6.CCR5–/–MPO–/– recipients rejected the grafts between days 46 and 54, with histopathological features of chronic graft injury. On day 15, myeloid cells infiltrating grafts from B6.CCR5–/– and B6.CCR5–/–MPO–/– recipients expressed marked phenotypic and functional transcript differences that correlated with the development of acute versus chronic allograft injury, respectively. Near the time of peak DSA titers, activation of NK cells to proliferate and express CD107a was decreased within allografts in B6.CCR5–/–MPO–/– recipients. Despite high titers of DSA, depletion of neutrophils reproduced the inhibition of NK cell activation and decreased macrophage infiltration but increased monocytes producing MPO. Overall, recipient myeloid cells producing MPO regulate graft-infiltrating monocyte/macrophage function and NK cell activation that are required for DSA-mediated acute kidney allograft injury, and their absence switches DSA-mediated acute pathology and graft outcomes to chronic ABMR.

MO065DIAGNOSTIC CRITERIA OF HUMORAL REJECTION IN RENAL TRANSPLANT RECIPIENTS WITH PRE-EXISTING ANTI-HLA ANTIBODIES BASED ON SENTINEL SKIN FLAP BIOPSY

Abstract Background and Aims Twenty years of transplantation of composite vascularised allografts have revealed the high immunogenicity of the constituent parts, especially the skin.Several researchers have proposed the use of vascular stalk flaps, which allow to performe skin biopsy and diagnose rejection without biopsy of the transplanted solid organ.Pre-existing anti-HLA antibodies represent a serious immunological barrier to successful kidney transplantation.We are not aware of any studies on the diagnosis of antibody-associated acute kidney allograft rejection from deceased donors in recipients with pre-existing antibodies, based on morphological examination of a sentinel skin flap on a vascular stalk. The Aim: To determine the morphological features of humoral rejection in renal transplant recipients with pre-existing anti-HLA antibodies based on sentinel skin flap biopsy. Method Three skin-kidney allografts recipients underwent skin flap biopsy on 2nd day after transplantation. A kidney allograft biopsy was performed on day 7, 30, 60, 90.The results of morphological studies are presented using the Banff classification of renal allograft and skin allograft pathology. All recipients were female; 35, 44, and 57 years old. Two patients were re-transplanted and the main cause of CKD was chronic glomerulonephritis. The third patient, with congenital abnormality of the urinary tract, received her first graft.Pre-existing anti-HLA antibody levels before transplantation were 50%, 60%, 80%, respectively. Results All recipients showed signs of humoral rejection of the skin flap with thrombosis of the feeding vascular bundle, phlebitis, predominantly intimal arteritis with median necrosis, detachment and areactive necrosis of epidermis and epithelium of skin appendages. Clinical rejection, similar to the algorithm proposed by Etra J.W. et al. to assess preclinical skin rejection in an animal model (2019), was interpreted as G2 in two cases and G3 in one case. The Banff classification of the skin flap offers a qualitative assessment of certain biopsy parameters, while the kidney graft has qualitative-quantitative criteria for assessing rejection. When comparing the two classifications, a quantitative gradation of pathological changes in the skin flap according to the parameter of intimal arteritis (v) and immunoreactivity of the C4d marker similar to renal rejection was possible. In histological examination of skin flap biopsies, the degree of vasculitis was assessed in a large feeding artery: in all three cases this parameter was equal to v3. C4d expression was analyzed in the endothelium of microcirculatory blood vessels of the dermis and hypodermis: C4d1 in one case and C4d3 in the other two. The analysis of renal allograft biopsies revealed signs of humoral rejection (v1) only at day 30 in two recipients whose C4d expression in the skin and hypodermis was strong (C4d3). Conclusion Antibody-mediated rejection of a vascularized sentinel skin flap in recipients with combined skin-kidney transplantation is characterized by vasculitis affecting a core vascular bundle in the form of endarteritis with necrosis of media,phlebitis and associated thrombosis.Further studies are required to determine the feasibility of using a vascular stalked skin flap in the diagnosis of humoral rejection after renal transplantation.

Chemokine Profiles Are Affected in Serum of Patients with Acute Rejection of Kidney Allograft.

Kidney allograft transplantation improved the prognosis and quality of life of patients with end-stage renal diseases but the occurrence of acute rejection represents a limitation of the final outcome. Noninvasive biomarkers are needed as well as further advancements in the understanding of immune mechanisms of reaction to the allograft. Our study of 138 patients focused on one-year monitoring of serum concentrations of 12 chemokines regulating the recruitment of different immune cells into transplanted allograft and on in vitro regulation of the same chemokines release by interactions of renal proximal epithelial cells with monocyte/macrophage cell line stimulated with TNF alpha. In a group of 44 patients with acute rejection, higher serum pretransplant levels of CXCL1, CXCL5, CXCL6, CCL2, CCL21, and particularly CXCL10 and CX3CL1(both p < 0.001) were found suggesting their higher proinflammatory status as compared to subjects with the uncomplicated outcome. In samples collected at the day of biopsy positive for acute rejection, chemokines CXCL9 and CXCL11 attracting preferentially Th1 lymphocytes were found to be upregulated. In our in vitro model with TNF alpha induction, renal proximal epithelial cells seemed to be a more potent source of chemokines attracting neutrophils as compared to monocyte/macrophage cell line but the coculture of these cells potentiated release of neutrophilic chemokines CXCL5 and CXCL6. Similar augmentation of chemokine production was found also in the case of CCL2. On the other hand, adding of monocytes/macrophages to a culture of renal epithelial cells suppressed the release of CXCL10 and CXCL11 attracting T lymphocytes. We assume from our data that in kidney allograft transplantation, chemokines attracting neutrophils, T lymphocytes, and monocytes are induced simultaneously and measurement some of them in combination might be used as biomarkers of acute rejection. Mutual cell-cell interactions of immune cells with renal parenchyma seem to be important for fine regulation of chemokine release.

Urinary Biomarkers for Diagnosis and Prediction of Acute Kidney Allograft Rejection: A Systematic Review.

Noninvasive tools for diagnosis or prediction of acute kidney allograft rejection have been extensively investigated in recent years. Biochemical and molecular analyses of blood and urine provide a liquid biopsy that could offer new possibilities for rejection prevention, monitoring, and therefore, treatment. Nevertheless, these tools are not yet available for routine use in clinical practice. In this systematic review, MEDLINE was searched for articles assessing urinary biomarkers for diagnosis or prediction of kidney allograft acute rejection published in the last five years (from 1 January 2015 to 31 May 2020). This review follows the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles providing targeted or unbiased urine sample analysis for the diagnosis or prediction of both acute cellular and antibody-mediated kidney allograft rejection were included, analyzed, and graded for methodological quality with a particular focus on study design and diagnostic test accuracy measures. Urinary C-X-C motif chemokine ligands were the most promising and frequently studied biomarkers. The combination of precise diagnostic reference in training sets with accurate validation in real-life cohorts provided the most relevant results and exciting groundwork for future studies.

Development of cell-free platform-based toehold switch system for detection of IP-10 mRNA, an indicator for acute kidney allograft rejection diagnosis

Quantitative PCR and droplet digital PCR were elucidated as non-invasive methods for quantifying the level of signaling markers, such as CD3ɛ and IP-10 mRNAs from urine samples, for the diagnosis of acute rejection in the kidney allograft recipients. Although the sensitivity and accuracy make PCR as the gold standard for diagnosis, a point-of-care (POC) testing is required for the rapid and low-cost preliminary prognosis and diagnosis. In this study, the applicability of the cell-free platform-based toehold switch system was preliminary demonstrated for the detection of synthetic IP-10 mRNA, one of indicators of acute kidney allograft rejection. For POC applications, the colorimetric output was utilized for direct recognition by naked eyes. A total of 5 switches was screened from 289 putative toehold switches. Among these, the toehold switch 4 illustrated the highest fold change after a 45-min incubation with relatively high specificity. The sensitivity of the toehold switch 4 was also demonstrated with the cognate IP-10 mRNA. The results in this study showed the feasibility of the synthetic system of RNA toehold switches in combination with the cell-free platform as a preliminary prognostic and diagnostic method for acute kidney allograft rejection.

Ischemia Reperfusion Injury Triggers CXCL13 Release and B-Cell Recruitment After Allogenic Kidney Transplantation.

Ischemia reperfusion injury (IRI) is linked with inflammation in kidney transplantation (ktx). The chemokine CXCL13, also known as B lymphocyte chemoattractant, mediates recruitment of B cells within follicles of lymphoid tissues and has recently been identified as a biomarker for acute kidney allograft rejection. The goal of this study was to explore whether IRI contributes to the up-regulation of CXCL13 levels in ktx. It is demonstrated that systemic levels of CXCL13 were increased in mouse models of uni- and bilateral renal IRI, which correlated with the duration of IRI. Moreover, in unilateral renal IRI CXCL13 expression in ischemic kidneys was up-regulated. Immunohistochemical studies revealed infiltration of CD22+ B-cells and, single-cell RNA sequencing analysis a higher number of cells expressing the CXCL13 receptor CXCR5, in ischemic kidneys 7 days post IRI, respectively. The potential relevance of these findings was also evaluated in a mouse model of ktx. Increased levels of serum CXCL13 correlated with the lengths of cold ischemia times and were further enhanced in allogenic compared to isogenic kidney transplants. Taken together, these findings indicate that IRI is associated with increased systemic levels of CXCL13 in renal IRI and ktx.

P1608CXCL13 IS STRONGLY INDUCED BY RENAL ISCHEMIA REPERFUSION INJURY AND CORRELATES WITH SEVERITY OF RENAL INFLAMMATION

Abstract Background and Aims Ischemia reperfusion injury (IRI) is a strong trigger of inflammation and is tightly linked to renal allograft damage and function. CXCL13 or B lymphocyte chemoattractant (BLC) is a chemokine that controls B cell organization in lymphoid tissues and has recently been described as a biomarker for B cell involvement in acute kidney allograft rejection. Method To show, that CXCL13 is already induced by IRI alone we used renal IRI models in mice with different ischemia times and a kidney transplantation model. We measured serum CXCL13 and characterized cell infiltrates by immunohistochemistry and performed single cell RNA sequencing. Allogenic and isogenic kidney transplantation (KTX) in mice was done to evaluate these findings in the transplant setting. Results Systemic CXCL13 levels increased within hours after surgery in a time dependent manner, both after induction of IRI and KTX. Levels of CXCL13 increased with duration of ischemia time and were higher in allogenic than isogenic transplantation with equal duration of ischemia. CXCR5, the receptor for CXCL13, is mainly expressed on B lymphocytes but also on a subset of T lymphocytes and macrophages. CXCR5 positive infiltrates were detected in IRI kidneys seven days after injury. In kidney allografts interstitial B cell infiltrates were observed as early as seven days and increased further towards three weeks after KTX. Conclusion The current findings indicate that IRI is a strong trigger of CXCL13 expression in the kidney and release into the circulation, which is followed by B lymphocyte infiltration into damaged tissue in ischemic and renal allografts.

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

18F-FDG PET/CT imaging may help non-invasively disprove the diagnosis of acute kidney allograft rejection (AR) in kidney transplant recipients (KTR). The present study aims at evaluating the repeatability and reproducibility of the quantification of renal 18F-FDG uptake in KTR. We prospectively performed 18F-FDG PET/CT in 95 adult KTR who underwent surveillance transplant biopsy between 3 to 6 months post transplantation. Images were obtained 180 minutes after injecting 3 MBq 18F-FDG per kg body weight. Mean standard uptake value (SUVmean) of kidney cortex was independently measured by 2 experienced observers in 4 volumes of interest (VOI) distributed in the upper (n = 2) and lower (n = 2) poles. The first observer repeated SUV assessment in the uppermost VOI, blinded to the initial results. Intra-class correlation coefficients (ICC) and Bland-Altman plots were calculated. An ICC of 0.96 with 95%CI of [0.94; 0.97] was calculated for the intra-observer measurements. The ICC for inter-observer reproducibility for each VOI was 0.87 [0.81–0.91], 0.87 [0.81–0.91], 0.85 [0.78–0.89] and 0.83 [0.76–0.88] for the upper to the lower renal poles, respectively. The repeatability and reproducibility of the quantification of kidney allograft 18F-FDG uptake are both consistent, which makes it transferrable to the clinical routine.