• acute rejection
• cadaveric transplantation
• expanded-criteria donors
• mycophenolate mofetil

• cost-effectiveness
• real-world
• rabbit antithymocyte globulin
• kidney transplantation

• Kidney Transplantation/economics
• Kidney Transplantation/adverse effects
• Antilymphocyte Serum/economics
• Antilymphocyte Serum/therapeutic use
• Cost-Benefit Analysis
• Humans
• Graft Rejection/prevention & control
• Male
• Female
• Middle Aged
• Adult
• Immunosuppressive Agents/economics
• Immunosuppressive Agents/therapeutic use
• Graft Survival/drug effects
• Cost-Effectiveness Analysis

• end-stage kidney disease
• fatty acids
• kidney transplant
• nutrition

• Humans
• Kidney Transplantation/adverse effects
• Male
• Female
• Fatty Acids/blood
• Middle Aged
• Adult
• Renal Insufficiency, Chronic/blood
• Time Factors
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/blood
• Cardiovascular Diseases/prevention & control

• ST-89 Gdańsk Medical University
• ST-40 Gdańsk Medical University

• Acute rejection
• chronic rejection
• kidney transplantation
• proteomic analysis
• urinary endovesicles

• Humans
• Kidney Transplantation
• Graft Rejection/diagnosis
• Graft Rejection/urine
• Graft Rejection/immunology
• Proteomics/methods
• Biomarkers/urine
• Kidney Failure, Chronic/surgery

• graft survival
• kidney transplantation
• mortality
• patient adherence
• patient outcome assessment

• funding

• HLA matching
• biomarkers
• desensitization
• emerging therapies
• immunosuppression
• preventing rejection

• Mass cytometry
• Multiomics
• Single cell
• Solid organ transplantation
• Transplant immunology

• Humans
• Organ Transplantation/adverse effects
• Organ Transplantation/methods
• Immunosuppression Therapy
• Immune Tolerance
• T-Lymphocytes
• Biomarkers
• Graft Rejection/diagnosis

• K08 CA245220 NCI NIH HHS
• National Cancer Institute

• Artificial intelligence
• Kidney transplantation
• Machine learning
• Nephrology

• Austrian kidney transplant cohort
• allograft rejection
• clinical transplantation outcomes
• deceased donor kidney
• deceased donor transplant
• immunosuppression
• kidney allograft
• non-living kidney transplant

• biofluid
• capillary electrophoresis-mass spectrometry
• kidney transplantation
• metabolomics

• U.S. Department of Agriculture
• Natural Sciences and Engineering Research Council of Canada

Objective

The aim of our study was to evaluate the incidence, causes, risk factors, outcomes, and cost of hospital readmission after live related renal transplantation (LRRT).

Methods

We conducted a cross-sectional study and followed patients’ re-admissions for six months whose LRRT was done in our center between September 2019 and June 2020.

Results

We recruited 53 patients, 40 (75.5%) were male. The mean age was 36.9 ± 11.9 years. Donor gender was similar, and their mean age was 31.6 ± 9.2 years. The mean length of hospital stay after LRRT was 14 ± 2.2 days. A total of 81.1% were readmitted after LRRT within the first six months, with a total of 113 readmissions. The median time of readmission after LRRT was 66 days. The median readmission hospital stay was four days. The causes of readmission were surgical in 11 (9.7%), medical in 89 (78.8%), and combined medical and surgical in 13 (11.5%). Infection was the most common medical cause, followed by rejection. Statistically significant difference between readmission and non-readmission groups was found in estimated glomerular filtration rate (eGFR) at six month 61.3 ± 25.9 vs. 84.3 ± 36.1 mL/min/1.73 m² respectively (p = 0.02). The median cost of readmission was PKR 40629, equivalent to USD 261.

Conclusion

Over three-fourths of the patients were readmitted after LRRT within the first six months. The most common causes were infection and rejection. Readmissions after LRRT are associated with lower graft function at six months and a significant cost burden on the health system.

The oral health of organ transplanted patients before organ re-transplantation is largely unknown. This retrospective clinical study evaluates the necessity for intraoral surgical intervention and/or conservative treatment in candidates awaiting organ re-transplantation, both for graft failure and for reasons of another upcoming solid organ transplantation (renal or non-renal).

From January 2015 to March 2020 n = 19 transplant recipients in evaluation on the waiting list for solid organ re-transplantation could be included in the retrospective case series study. Using clinical and radiological examinations, necessity for oral surgical or conservative dental treatment was evaluated. On the basis of anamnesis data, current kidney function, renal replacement treatment (RRT), and medication, a risk profile for several patient subgroups was created.

The clinical and radiological examinations showed a conservative and/or surgical treatment need in n = 13 cases (68.42%). In n = 7 cases (36.84%) surgical intervention was recommended due to residual root remnants (n = 5), unclear mucosal changes (n = 1), and periimplantitis (n = 1). In n = 16 recipients (84.2%) RRT (n = 15 hemodialysis; n = 1 peritoneal dialysis) had been performed. N = 14 recipients (73.68%) received immunosuppressants. In n = 1 patient (5.3%) displayed intraoral and n = 4 patients (21.1%) extraoral neoplasms due to drug-induced immunosuppression.

Solid organ transplant recipients with renal failure present a complex treatment profile due to a double burden of uremia plus immunosuppressants. In cases of surgical treatment need a hospitalized setting is recommended, where potentially necessary follow-up care and close cooperation with disciplines of internal medicine is possible in order to avoid surgical and/or internal complications.

• Immunosuppression
• Oral health
• Organ transplantation

Serum creatinine is a commonly used laboratory marker to assess kidney function; however, there has not been an established level of serum creatinine to predict mortality. After extensive literature review, we present a case of the highest recorded serum creatinine of 73.8 mg/dL in a 23-year-old male with the history of pediatric deceased donor kidney transplant (DDKT). He initially presented with uremia and signs of acute renal allograft failure after two months of immunosuppressive medication nonadherence, ultimately requiring emergent hemodialysis, which was complicated by new onset seizures. This was the patient's fourth episode of late acute rejection and emphasizes the need for education of immunosuppressant adherence and periodic monitoring of renal function in high-risk patients. Though there is no known creatinine level incompatible with life, this patient appears to have the highest known serum creatinine in a uremic patient on record.

• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Case-Control Studies
• DNA/chemistry
• DNA/urine
• Databases, Genetic
• Female
• Graft Rejection/diagnosis
• High-Throughput Nucleotide Sequencing
• Humans
• Kidney/pathology
• Kidney Failure, Chronic/therapy
• Kidney Transplantation/adverse effects
• Male
• Middle Aged
• Sequence Analysis, DNA
• Tissue Donors
• Transplantation, Homologous
• Urine/cytology

• K08 DK087824 NIDDK NIH HHS
• R37 AI051652 NIAID NIH HHS
• National Institutes of Health
• Qatar National Research Fund
• Qatar Foundation

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 (SUV_mean) 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.

Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4⁺ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27Rα in grafts was detected. The radio-probe, ¹²⁵I-anti-IL-27Rα mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27Rα was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). ¹²⁵I-anti-IL-27Rα mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of ¹²⁵I-anti-IL-27Rα mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27Rα mAb. Interestingly, we found that ¹²⁵I-anti-IL-27Rα mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of ¹²⁵I-anti-IL-27Rα mAb was correlated with the higher infiltrated IL-27Rα positive cells (CD3⁺/CD68⁺) in allogeneic grafts. In conclusion, IL-27Rα may be a novel molecular imaging marker to predict allorejection.

• IL-27Rα 1
• allorejection 2
• autoradiography imaging 3
• biomarker 4
• radioiodine 5

Supplemental Digital Content is Available in the Text.

Monitoring and maintaining a stable tacrolimus trough level is essential because of its narrow therapeutic window and considerable fluctuation in the early phase after kidney transplantation. However, optimal tacrolimus exposure early after transplantation remains unclear among Chinese patients.

In this propensity score–matched cohort study, we thoroughly investigated the association between tacrolimus trough level at the first month and acute rejection (AR) as well as infection within the first year after kidney transplantation.

In a first step, a total of 1415 patients were divided into 3 groups according to the receiver operating characteristic curve: low-level group (410 patients with a tacrolimus trough level <5.35 ng/mL at the first month), median-level group (466 patients with a tacrolimus trough level from 5.35 to 7.15 ng/mL), and high-level group (539 patients with a tacrolimus trough level >7.15 ng/mL). Ultimately, 363 and 459 pairs of cases were enrolled by using 2 propensity score matches between low- and median-level groups and between high- and median-level groups, respectively. Compared with patients in the low-level group, patients in the median-level group had lower risk of AR without increased incidence of infection (AR, 12.4% versus 5.7%, P = 0.02; infection, 13.2% versus 13.2%, P = 1.00 for low- and median-level groups, respectively) within the first year. Compared with patients in the high-level group, patients in the median-level group had lower incidence of infection without the growing risk of AR (infection, 17.6% versus 12.2%, P = 0.021; AR, 4.6% versus 5.4%, P = 0.545 for high- and median-level groups, respectively) within the first year. Multilogistic analysis showed that tacrolimus trough levels were an independent factor for AR (odds ratio, 0.749, 95% confidence interval, 0.632–0.888, P = 0.001). Tacrolimus trough levels were also associated with infection (odds ratio 1.110, 95% confidence interval, 1.013–1.218, P = 0.001). Serum creatinine levels were similar among groups. No difference was found in 1-, 3-, and 5-year graft survival and patient survival among groups.

The tacrolimus trough level maintained between 5.35 and 7.15 ng/mL at the first posttransplant month may prevent AR without increasing the incidence of infection within the first year after living kidney transplantation among Chinese patients.

• Complications
• Kidney transplantation
• Magnetic resonance imaging
• Renal allograft

Medication non-adherence is a risk factor for acute kidney transplant rejection. The association of non-adherence with short-term allograft loss in patients who develop acute rejection and are subsequently treated with maximal therapy is unknown.

We conducted a retrospective single center cohort study of adult patients who developed acute rejection from January 2003 to December 2017 and were treated with lymphocyte depletion. Clinicopathologic characteristics including adherence status were collected and descriptive statistics utilized to compare groups. The primary outcome was all-cause graft loss at 6 months after acute rejection treatment. A multivariable logistic regression quantified the association of non-adherence with the outcome.

A total of 182 patients were included in the cohort, of whom 71 (39%) were non-adherent. Compared to adherent patients, non-adherent patients were younger (mean age 37y vs 42y), more likely to be female (51% vs 35%) and developed acute rejection later (median 2.3y vs 0.5y from transplant). There were no differences in estimated glomerular filtration rate or need for dialysis on presentation, Banff grade, or presence of antibody mediated rejection between the 2 groups. Overall, 48 (26%) patients lost their grafts at 6 months after acute rejection treatment. In adjusted analysis, non-adherence was associated with all-cause graft loss at 6 months after acute rejection treatment [OR 2.64 (95% CI 1.23–5.65, p = 0.012].

After adjusting for common confounders, non-adherent patients were at increased risk for short-term allograft loss after a severe acute rejection despite lymphocyte depletion. This finding may aid clinicians in risk stratifying patients for poor short-term outcomes and treatment futility.

• Acute rejection
• Graft loss
• Kidney transplantation
• Non-adherence

• Expression profiling
• NK cells
• Nephrology
• Organ transplantation
• Transplantation

• Acute allograft rejection
• MRI
• PET
• SPECT
• imaging
• kidney transplantation
• noninvasive
• ultrasound

To date, allogeneic kidney transplantation remains the best available therapeutic option for patients with end-stage renal disease regarding overall survival and quality of life. Despite the advancements in immunosuppressive drugs and protocols, episodes of acute allograft rejection, a sterile inflammatory process, continue to endanger allograft survival. Since effective treatment for acute rejection episodes is available, instant diagnosis of this potentially reversible graft injury is imperative. Although histological examination by invasive core needle biopsy of the graft remains the gold standard for the diagnosis of ongoing rejection, it is always associated with the risk of causing substantial graft injury as a result of the biopsy procedure itself. At the same time, biopsies are not immediately feasible for a considerable number of patients taking anticoagulants due to the high risk of complications such as bleeding and uneven distribution of pathological changes within the graft. This can result in the wrong diagnosis due to the small size of the tissue sample taken. Therefore, there is a need for a tool that overcomes these problems by being noninvasive and capable of assessing the whole organ at the same time for specific and fast detection of acute allograft rejection. In this article, we review current state-of-the-art approaches for noninvasive diagnostics of acute renal transplant inflammation, i.e., rejection. We especially focus on nonradiation-based methods using magnetic resonance imaging (MRI) and ultrasound.

• acute rejection
• graft failure
• intra-patient variability
• kidney transplant
• tacrolimus

• biopsy
• graft rejection
• immunosuppression
• polyomavirus
• risk factors

We aim to identify the key biomarker of acute rejection (AR) after kidney transplantation via bioinformatics methods.

The gene expression data GSE75693 of 30 samples with stable kidney transplantation recipients and 15 AR samples were downloaded and analyzed by the limma package to identify differentially expressed genes (DEGs). Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were done to explore the biological functions and potential important pathways of DEGs. Finally, protein-protein interactions (PPIs) and literature mining were applied to construct the cocitation network and to select the hub protein.

A total of 437 upregulated genes and 353 downregulated genes were selected according to P < 0.01 and |log₂(fold change)| > 1.0. DEGs of AR are mainly located on membranes and impact the activation of receptors in immune responses. In the PPI network, Src kinase, lymphocyte kinase (LCK), CD3G, B2M, interferon-γ, CD3D, tumor necrosis factor, VAV1, and CD3E in the T cell receptor signaling pathway were selected as important factors, and LCK was identified as the hub protein.

LCK, via acting on T-cell receptor, might be a potential therapeutic target for AR after kidney transplantation.

• Acute Disease
• Antibodies/therapeutic use
• Antibodies, Monoclonal/therapeutic use
• Antilymphocyte Serum/therapeutic use
• Drug Resistance
• Graft Rejection/drug therapy
• Humans
• Immunologic Factors/therapeutic use
• Immunosuppressive Agents/therapeutic use
• Kidney Transplantation
• Muromonab-CD3/therapeutic use
• Randomized Controlled Trials as Topic
• Rituximab/therapeutic use

• Adult
• Antibodies, Monoclonal/therapeutic use
• Area Under Curve
• Basiliximab
• Calcineurin Inhibitors/administration & dosage
• Drug Therapy, Combination
• Female
• Graft Rejection/epidemiology
• Graft Rejection/immunology
• Graft Rejection/prevention & control
• Humans
• Immunosuppressive Agents/therapeutic use
• Incidence
• Kidney Transplantation/adverse effects
• Male
• Middle Aged
• Mycophenolic Acid/administration & dosage
• Prednisolone/administration & dosage
• ROC Curve
• Recombinant Fusion Proteins/therapeutic use
• Retrospective Studies
• Risk Factors

• Molecular diagnostics
• acute rejection
• genomics
• graft monitoring
• indicators of immune response
• organ transplantation
• personalized transplant management
• proteomics
• transcriptomics

• Biomarkers
• Disease Management
• Gene Expression Profiling/methods
• Genomics/methods
• Graft Rejection/diagnosis
• Graft Rejection/genetics
• Graft Rejection/immunology
• Graft Rejection/metabolism
• Humans
• Immunosuppression Therapy/methods
• Molecular Diagnostic Techniques
• Precision Medicine/methods
• Proteomics/methods
• Transplantation Immunology

• R01 DK083447 NIDDK NIH HHS
• R56 DK083447 NIDDK NIH HHS

• Acute allograft rejection
• Imaging
• Kidney transplantation
• Magnetic resonance imaging
• Positron emission tomography
• Renal
• Single photon emission computed tomography
• Ultrasound