European Consensus on the Management of Sensitized Kidney Transplant Recipients: A Delphi Study.

An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific antibodies (DSA)-triggered antibody-mediated rejection (AMR) significantly contributes to kidney graft failure, especially in sensitized patients. The European Society for Organ Transplantation (ESOT) launched the ENGAGE initiative, categorizing sensitized candidates by AMR risk to improve patient care. A systematic review assessed induction and maintenance regimens as well as antibody removal strategies, with statements subjected to the Delphi methodology. A Likert-scale survey was distributed to 53 European experts (Nephrologists, Transplant surgeons and Immunologists) with experience in kidney transplant recipient care. A rate ≥75% with the same answer was considered consensus. Consensus was achieved in 95.3% of statements. While most recommendations aligned, two statements related to complement inhibitors for AMR prophylaxis lacked consensus. The ENGAGE consensus presents contemporary recommendations for desensitization and immunomodulation strategies, grounded in predefined risk categories. The adoption of tailored, patient-specific measures is anticipated to streamline the care of sensitized recipients undergoing renal allografts. While this approach holds the promise of enhancing transplant accessibility and fostering long-term success in transplantation outcomes, its efficacy will need to be assessed through dedicated studies.

Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.

The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics.

The XVI-th Banff Meeting for Allograft Pathology was held at Banff, Alberta, Canada, from 19th to 23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, premeeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a postmeeting survey, agreement was reached on the delineation of the following phenotypes: (1) "Probable antibody-mediated rejection (AMR)," which represents donor-specific antibodies (DSA)-positive cases with some histologic features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) "Microvascular inflammation, DSA-negative and C4d-negative," a phenotype of unclear cause requiring further study, which represents cases with microvascular inflammation not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.

Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients.

Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured using PCR in stable kidney transplant recipients at ≥1 year after transplantation, and smoking status and alcohol intake were assessed through questionnaires and measurements of urinary cotinine and ethyl glucuronide. A total of 666 KTRs were included (57% male). A total of 549 KTR (82%) had a detectable TTV load (3.1 ± 1.5 log10 copies/mL). In KTR with a detectable TTV load, cyclosporin and tacrolimus use were positively associated with TTV load (St. ß = 0.46, p < 0.001 and St. ß = 0.66, p < 0.001, respectively), independently of adjustment for potential confounders. Current smoking and alcohol intake of >20 g/day were negatively associated with TTV load (St. ß = -0.40, p = 0.004 and St. ß = -0.33, p = 0.009, respectively), independently of each other and of adjustment for age, sex, kidney function, time since transplantation and calcineurin inhibitor use. This strong association of smoking and alcohol intake with TTV suggests a need to account for the smoking status and alcohol intake when applying TTV guided immunosuppression in KTR.

Report of the 2022 Banff Heart Concurrent: Focus on non-human leukocyte antigen antibodies in rejection and the pathology of "mixed" rejection.

The Banff Heart Concurrent Session, held as part of the 16th Banff Foundation for Allograft Pathology Conference at Banff, Alberta, Canada, on September 21, 2022, focused on 2 major topics: non-human leukocyte antigen (HLA) antibodies and mixed rejection. Each topic was addressed in a multidisciplinary fashion with clinical, immunological, and pathology perspectives and future developments and prospectives. Following the Banff organization model and principles, the collective aim of the speakers on each topic was to • Determine current knowledge gaps in heart transplant pathology • Identify limitations of current pathology classification systems • Discuss next steps in addressing gaps and refining classification system.

Imlifidase for Kidney Transplantation of Highly Sensitized Patients With a Positive Crossmatch: The French Consensus Guidelines.

Imlifidase recently received early access authorization for highly sensitized adult kidney transplant candidates with a positive crossmatch against an ABO-compatible deceased donor. These French consensus guidelines have been generated by an expert working group, in order to homogenize patient selection, associated treatments and follow-up. This initiative is part of an international effort to analyze properly the benefits and tolerance of this new costly treatment in real-life. Eligible patients must meet the following screening criteria: cPRA ≥ 98%, ≤ 65-year of age, ≥ 3 years on the waiting list, and a low risk of biopsy-related complications. The final decision to use Imlifidase will be based on the two following criteria. First, the results of a virtual crossmatch on recent serum, which shall show a MFI for the immunodominant donor-specific antibodies (DSA) > 6,000 but the value of which does not exceed 5,000 after 1:10 dilution. Second, the post-Imlifidase complement-dependent cytotoxicity crossmatch must be negative. Patients treated with Imlifidase will receive an immunosuppressive regimen based on steroids, rATG, high dose IVIg, rituximab, tacrolimus and mycophenolic acid. Frequent post-transplant testing for DSA and systematic surveillance kidney biopsies are highly recommended to monitor post-transplant DSA rebound and subclinical rejection.

Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection.

Rejection remains the main cause of premature graft loss after kidney transplantation, despite the use of potent immunosuppression. This highlights the need to better understand the composition and the cell-to-cell interactions of the alloreactive inflammatory infiltrate. Here, we performed droplet-based single-cell RNA sequencing of 35,152 transcriptomes from 16 kidney transplant biopsies with varying phenotypes and severities of rejection and without rejection, and identified cell-type specific gene expression signatures for deconvolution of bulk tissue. A specific association was identified between recipient-derived FCGR3A+ monocytes, FCGR3A+ NK cells and the severity of intragraft inflammation. Activated FCGR3A+ monocytes overexpressed CD47 and LILR genes and increased paracrine signaling pathways promoting T cell infiltration. FCGR3A+ NK cells overexpressed FCRL3, suggesting that antibody-dependent cytotoxicity is a central mechanism of NK-cell mediated graft injury. Multiplexed immunofluorescence using 38 markers on 18 independent biopsy slides confirmed this role of FcγRIII+ NK and FcγRIII+ nonclassical monocytes in antibody-mediated rejection, with specificity to the glomerular area. These results highlight the central involvement of innate immune cells in the pathogenesis of allograft rejection and identify several potential therapeutic targets that might improve allograft longevity.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Prior SARS-CoV-2 infection enhances and reshapes spike protein-specific memory induced by vaccination.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Subclinical rejection-free diagnostic after kidney transplantation using blood gene expression.

We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA. From 441 patients with protocol biopsy, there was a significant decrease of the score of tolerance in 45 patients with biopsy-proven subclinical rejection (SCR), a major threat associated with pejorative allograft outcomes that prompted an SCR score refinement. This refinement used only two genes, AKR1C3 and TCL1A, and four clinical parameters (previous experience of rejection, previous transplantation, sex of recipient and tacrolimus uptake). This refined SCR score was able to identify patients unlikely to develop SCR with a C-statistic of 0.864 and a negative predictive value of 98.3%. The SCR score was validated in an external laboratory, with two methods (qPCR and NanoString), and on 447 patients from an independent and multicenter cohort. Moreover, this score allowed reclassifying patients with discrepancies between the DSA presence and the histological diagnosis of antibody mediated rejection unlike kidney function. Thus, our refined SCR score could improve detection of SCR for closer and noninvasive monitoring, allowing early treatment of SCR lesions notably for patients DSA-positive and during lowering of immunosuppressive treatment.

mTOR Activation Underlies Enhanced B Cell Proliferation and Autoimmunity in PrkcdG510S/G510S Mice.

Autosomal recessive PRKCD deficiency has previously been associated with the development of systemic lupus erythematosus in human patients, but the mechanisms underlying autoimmunity remain poorly understood. We introduced the Prkcd G510S mutation that we previously associated to a Mendelian cause of systemic lupus erythematosus in the mouse genome, using CRISPR-Cas9 gene editing. PrkcdG510S/G510S mice recapitulated the human phenotype and had reduced lifespan. We demonstrate that this phenotype is linked to a B cell-autonomous role of Prkcd. A detailed analysis of B cell activation in PrkcdG510S/G510S mice shows an upregulation of the PI3K/mTOR pathway after the engagement of the BCR in these cells, leading to lymphoproliferation. Treatment of mice with rapamycin, an mTORC1 inhibitor, significantly improves autoimmune symptoms, demonstrating in vivo the deleterious effect of mTOR pathway activation in PrkcdG510S/G510S mice. Additional defects in PrkcdG510S/G510S mice include a decrease in peripheral mature NK cells that might contribute to the known susceptibility to viral infections of patients with PRKCD mutations.

Machine learning does not outperform traditional statistical modelling for kidney allograft failure prediction.

Machine learning (ML) models have recently shown potential for predicting kidney allograft outcomes. However, their ability to outperform traditional approaches remains poorly investigated. Therefore, using large cohorts of kidney transplant recipients from 14 centers worldwide, we developed ML-based prediction models for kidney allograft survival and compared their prediction performances to those achieved by a validated Cox-Based Prognostication System (CBPS). In a French derivation cohort of 4000 patients, candidate determinants of allograft failure including donor, recipient and transplant-related parameters were used as predictors to develop tree-based models (RSF, RSF-ERT, CIF), Support Vector Machine models (LK-SVM, AK-SVM) and a gradient boosting model (XGBoost). Models were externally validated with cohorts of 2214 patients from Europe, 1537 from North America, and 671 from South America. Among these 8422 kidney transplant recipients, 1081 (12.84%) lost their grafts after a median post-transplant follow-up time of 6.25 years (Inter Quartile Range 4.33-8.73). At seven years post-risk evaluation, the ML models achieved a C-index of 0.788 (95% bootstrap percentile confidence interval 0.736-0.833), 0.779 (0.724-0.825), 0.786 (0.735-0.832), 0.527 (0.456-0.602), 0.704 (0.648-0.759) and 0.767 (0.711-0.815) for RSF, RSF-ERT, CIF, LK-SVM, AK-SVM and XGBoost respectively, compared with 0.808 (0.792-0.829) for the CBPS. In validation cohorts, ML models' discrimination performances were in a similar range of those of the CBPS. Calibrations of the ML models were similar or less accurate than those of the CBPS. Thus, when using a transparent methodological pipeline in validated international cohorts, ML models, despite overall good performances, do not outperform a traditional CBPS in predicting kidney allograft failure. Hence, our current study supports the continued use of traditional statistical approaches for kidney graft prognostication.

Plasma endotrophin, reflecting tissue fibrosis, is associated with graft failure and mortality in KTRs: results from two prospective cohort studies.

BACKGROUND: Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs. METHODS: In cohort A (57% male, age 53 ± 13 years), we measured plasma endotrophin in 690 prevalent KTRs ≥1 year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin. RESULTS: In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07-3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73-3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7-7.6)]. CONCLUSIONS: Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02811835.

Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant Biopsies.

BACKGROUND: No validated system currently exists to realistically characterize the chronic pathology of kidney transplants that represents the dynamic disease process and spectrum of disease severity. We sought to develop and validate a tool to describe chronicity and severity of renal allograft disease and integrate it with the evaluation of disease activity. METHODS: The training cohort included 3549 kidney transplant biopsies from an observational cohort of 937 recipients. We reweighted the chronic histologic lesions according to their time-dependent association with graft failure, and performed consensus k-means clustering analysis. Total chronicity was calculated as the sum of the weighted chronic lesion scores, scaled to the unit interval. RESULTS: We identified four chronic clusters associated with graft outcome, based on the proportion of ambiguous clustering. The two clusters with the worst survival outcome were determined by interstitial fibrosis and tubular atrophy (IFTA) and by transplant glomerulopathy. The chronic clusters partially overlapped with the existing Banff IFTA classification (adjusted Rand index, 0.35) and were distributed independently of the acute lesions. Total chronicity strongly associated with graft failure (hazard ratio [HR], 8.33; 95% confidence interval [CI], 5.94 to 10.88; P<0.001), independent of the total activity scores (HR, 5.01; 95% CI, 2.83 to 7.00; P<0.001). These results were validated on an external cohort of 4031 biopsies from 2054 kidney transplant recipients. CONCLUSIONS: The evaluation of total chronicity provides information on kidney transplant pathology that complements the estimation of disease activity from acute lesion scores. Use of the data-driven algorithm used in this study, called RejectClass, may provide a holistic and quantitative assessment of kidney transplant injury phenotypes and severity.

Absence of Mortality Differences Between the First and Second COVID-19 Waves in Kidney Transplant Recipients.

Introduction: SARS-CoV-2 pandemic evolved in 2 consecutive waves during 2020. Improvements in the management of COVID-19 led to a reduction in mortality rates among hospitalized patients during the second wave. Whether this progress benefited kidney transplant recipients (KTRs), a population particularly vulnerable to severe COVID-19, remained unclear. Methods: In France, 957 KTRs were hospitalized for COVID-19 in 2020 and their data were prospectively collected into the French Solid Organ Transplant (SOT) COVID registry. The presentation, management, and outcomes of the 359 KTRs diagnosed during the first wave were compared to those of the 598 of the second wave. Results: Baseline comorbidities were similar between KTRs of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs. 58.4%, P < 0.001) or calcineurin inhibitor (32.1% vs. 16.6%, P < 0.001) was less frequent during the second wave. Hydroxychloroquine and azithromycin that were commonly used during the first wave (21.7% and 30.9%, respectively) but were almost abandoned during the second wave. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, P < 0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, P = 0.48) and COVID-19 hospitalization period was not associated with death due to COVID-19 in multivariate analysis (Hazard ratio 0.89, 95% confidence interval 0.67-1.17, P = 0.4). Conclusion: We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality among KTRs. Our data indirectly support the importance of vaccination and neutralizing monoclonal anti-SARS-CoV-2 antibodies to protect KTRS from severe COVID-19.

Inverted direct allorecognition triggers early donor-specific antibody responses after transplantation.

The generation of antibodies against donor-specific major histocompatibility complex (MHC) antigens, a type of donor-specific antibodies (DSAs), after transplantation requires that recipient's allospecific B cells receive help from T cells. The current dogma holds that this help is exclusively provided by the recipient's CD4+ T cells that recognize complexes of recipient's MHC II molecules and peptides derived from donor-specific MHC alloantigens, a process called indirect allorecognition. Here, we demonstrated that, after allogeneic heart transplantation, CD3ε knockout recipient mice lacking T cells generate a rapid, transient wave of switched alloantibodies, predominantly directed against MHC I molecules. This is due to the presence of donor CD4+ T cells within the graft that recognize intact recipient's MHC II molecules expressed by B cell receptor-activated allospecific B cells. Indirect evidence suggests that this inverted direct pathway is also operant in patients after transplantation. Resident memory donor CD4+ T cells were observed in perfusion liquids of human renal and lung grafts and acquired B cell helper functions upon in vitro stimulation. Furthermore, T follicular helper cells, specialized in helping B cells, were abundant in mucosa-associated lymphoid tissue of lung and intestinal grafts. In the latter, more graft-derived passenger T cells correlated with the detection of donor T cells in recipient's circulation; this, in turn, was associated with an early transient anti-MHC I DSA response and worse transplantation outcomes. We conclude that this inverted direct allorecognition is a possible explanation for the early transient anti-MHC DSA responses frequently observed after lung or intestinal transplantations.

Hamster organotypic kidney culture model of early-stage SARS-CoV-2 infection highlights a two-step renal susceptibility.

Kidney pathology is frequently reported in patients hospitalized with COVID-19, the pandemic disease caused by the Severe acute respiratory coronavirus 2 (SARS-CoV-2). However, due to a lack of suitable study models, the events occurring in the kidney during the earliest stages of infection remain unknown. We have developed hamster organotypic kidney cultures (OKCs) to study the early stages of direct renal infection. OKCs maintained key renal structures in their native three-dimensional arrangement. SARS-CoV-2 productively replicated in hamster OKCs, initially targeting endothelial cells and later disseminating into proximal tubules. We observed a delayed interferon response, markers of necroptosis and pyroptosis, and an early repression of pro-inflammatory cytokines transcription followed by a strong later upregulation. While it remains an open question whether an active replication of SARS-CoV-2 takes place in the kidneys of COVID-19 patients with AKI, our model provides new insights into the kinetics of SARS-CoV-2 kidney infection and can serve as a powerful tool for studying kidney infection by other pathogens and testing the renal toxicity of drugs.

Pretransplant characteristics of kidney transplant recipients that predict posttransplant outcome.

Better characterization of the potential kidney transplant recipient using novel biomarkers, for example, pretransplant plasma endotrophin, will lead to improved outcome after transplantation. This mini-review will focus on current knowledge about pretransplant recipients' characteristics, biomarkers, and immunology. Clinical characteristics of recipients including age, obesity, blood pressure, comorbidities, and estimated survival scores have been introduced for prediction of recipient and allograft survival. The pretransplant immunologic risk assessment include histocompatibility leukocyte antigens (HLAs), anti-HLA donor-specific antibodies, HLA-DQ mismatch, and non-HLA antibodies. Recently, there has been the hope that pretransplant determination of markers can further improve the prediction of posttransplant complications, both short-term and long-term outcomes including rejections, allograft loss, and mortality. Higher pretransplant plasma endotrophin levels were independently associated with posttransplant acute allograft injury in three prospective European cohorts. Elevated numbers of non-synonymous single-nucleotide polymorphism mismatch have been associated with increased allograft loss in a multivariable analysis. It is concluded that there is a need for integration of clinical characteristics and novel molecular and immunological markers to improve future transplant medicine to reach better diagnostic decisions tailored to the individual patient.