Risk Factor For Graft Loss Research Articles

Graft Loss in Pediatric and Young Adult Kidney Transplantation in New Zealand: Who Is at Greatest Risk and When?

Much is reported regarding the detrimental effect of transfer to adult services for adolescent and young adult (AYA) kidney transplant (KT) recipients. However, AYA recipient age independent of time post-KT, and not relating to transfer of care, is also a strong predictor of graft loss. We assessed KT graft survival if experiencing solely pediatric (PO) or adult services (AO) versus transfer from pediatric to adult services (PTA). A retrospective cohort analysis of all first kidney transplant recipients between birth-24 years of age, from 2000 to 2019 in New Zealand. Participant identification and data were obtained via the Australia and New Zealand Dialysis and Transplantation registry. Primary outcome was graft survival stratified by service type. Cox proportional hazard modeling assessed independent risk factors of graft loss. Two hundred forty-four children and AYA with a median follow-up of 7.3 years were included. Graft survival stratified by service provision group was not different. The incidence rate of graft loss was 37, 34, and 45 per 1000 persons per year for PO, PTA, and AO respectively. Crude age-specific graft failure rates were highest for 22-24-year-olds with inferior outcomes starting from age 16, peaking at 24 years. Older adolescence and young adulthood reflect a high-risk period for KT loss. Transfer to adult services was not associated with worse graft survival compared to those experiencing either AO or PO alone. Improved models of care are needed to improve graft survival in this vulnerable population within New Zealand.

Clinical outcomes after a biopsy diagnosis of antibody-mediated rejection in pediatric heart transplant recipients

BackgroundExtending graft survival after heart transplant (HT) is of paramount importance to achieve survival well into adulthood for childhood recipients. Acute rejection is a significant adverse event, and biopsy remains the most specific means for diagnosing acute cellular rejection (ACR) versus antibody-mediated rejection (AMR). MethodsAll children in the Pediatric Heart Transplant Society (PHTS) Registry who underwent HT between 1/2015 and 6/2022 and had ≥1 episode of treated rejection were included. Survival after rejection was compared between those with AMR and those with ACR-only. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) were assessed. Risk factors for graft loss after AMR were identified using Cox proportional hazard modeling. ResultsAmong 906 children treated for rejection during follow-up through 12/2022, 697 (77%) with complete biopsy information were included. AMR was present on biopsy in 261 (37%) patients; ACR-only was present in 436 (63%) patients. Time to treated rejection was earlier in those with AMR, median time from HT to rejection 0.11 versus 0.29 years, p=0.0006. When rejection occurred within the 1st year, survival after AMR was lower than survival after ACR-only. Predictors of graft loss after AMR were younger age at HT, diagnosis of congenital heart disease, and rejection with hemodynamic compromise. There was no difference in time to CAV, infection, or malignancy after treated rejection between groups. ConclusionsThe largest analysis of pediatric HT recipients treated for rejection with biopsy data to identify AMR underscores the continued importance of AMR on survival. AMR is associated with higher graft loss versus ACR when occurring in the first-year post HT. Predictors of graft loss after AMR identify patients who may benefit from increased surveillance, more aggressive rejection treatment, or augmented maintenance immunosuppression.

#3036 The influence of first renal graft on second graft rejection and survival: the importance of revisiting histocompatibility and clinical outcomes

Abstract Background and Aims Kidney retransplantation confers a robust survival benefit over dialysis and recent data has shown similar outcomes to first kidney transplant. The number of HLA mismatches is an important predictor of graft loss and sensitization and the presence of donor specific antibodies (DSA) -pre and -post transplant is a major risk factor for rejection and worst outcomes. However, the importance of HLA matching of first graft and the relevance of first donor DSAs on second graft outcomes is less known. Our aim was to identify risk factors to second graft acute rejection and graft loss, related to second and first graft features. Method We performed a retrospective, longitudinal study including all patients submitted to a 2nd kidney transplant between January 2008 and December 2021, excluding patients with more than 2 grafts or multi-organ transplant. Clinical and histocompatibility data from the first and second donor and recipient were collected. HLA antibodies were detected by solid phase assays and considered if MFI >2500. For subsequent kidney transplants, repeated mismatches are not allowed and unacceptable antigens are those for which the patient has pre-formed -A, -B and -DR antibodies, with MFI>1000. Biopsy proven acute rejection was defined according to Banff 2017 criteria. Follow-up was 31st December 2023 for functioning grafts or time to graft failure, with a mean time of 92 ± 53 months. Results We included 114 patients, 73 (64%) males, mostly Caucasians (96%), with a mean age of 43.9 ± 13 years at 2nd transplant. First kidney transplant was performed before 2010 for 99 patients (87%), with a median first graft survival of 82.5 [12.5-144] months and 19 patients (16.7%) presented primary disfunction due to surgical/vascular complications. After graft loss, 43 patients (37.7%) had their graft removed. For second transplant, 11 (9.6%) patients had a living donor. Induction therapy with thymoglobulin occurred in 94 patients (83%) and maintenance therapy with mycophenolic acid, calcineurin inhibitors and steroids was prescribed in 83 patients (73%). During follow-up, 20 patients (17.5%) presented biopsy proven acute rejection, 13 (65%) T cell mediated and 7 (35%) antibody-mediated, the majority during the first-year post-transplant (N = 17, 85%). The risk factors for second graft rejection are summarized in Table 1. Patients with a first graft nephrectomy had a higher risk of acute rejection (OR 3.9, 95% CI [1.4-10.9], p < 0.006) and were more susceptible to the development of second donor post-transplant DSA (58% vs 35%, p = 0.02). Death censored second allograft loss occurred in 24 patients (21%) at follow up and acute rejection was an important risk factors (OR 4.3, 95% CI [1.5-12.1], p = 0.004). First-year graft survival was 93% and a survival at follow up was 79%. On survival analysis the presence of second graft DSA was a major risk factor for graft loss, especially class 2 -DQ and -DR. First transplant total mismatch load, especially on class 1 contributed to worst graft survival. Conclusion Worst outcomes in first kidney transplant were related with an increased risk of acute rejection in second graft and 1st graft nephrectomy increases the risk of the development of 2nd graft DSA and acute rejection. First transplant mismatch load decreased second graft survival.

Characteristics of Delayed Graft Function and Long-Term Outcomes After Kidney Transplantation From Brain-Dead Donors: A Single-Center and Multicenter Registry-Based Retrospective Study.

Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland (n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry (n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14-1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01-1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99-1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors.

What Are Risk Factors for Graft Loss in Patients Who Underwent Simultaneous Splenectomy During Living-donor Liver Transplantation?

The consensus that portal venous pressure modulation, including splenectomy (Spx), prevents portal hypertension-related complications after living-donor liver transplantation (LDLT) has been established. However, little evidence about the risk factors for graft loss after simultaneous Spx during LDLT is available. This study aimed to identify the independent predictors of graft loss after simultaneous Spx during LDLT. Data of 655 recipients who underwent LDLT between 1997 and 2021 were collected and separated into the simultaneous Spx group (n = 461) and no-Spx group (n = 194). The simultaneous Spx group had significantly lower serum total bilirubin levels, drained ascites volumes, and prothrombin time-international normalized ratios on postoperative day 14 than the no-Spx group ( P < 0.001 for each). Incidences of small-for-size graft syndrome ( P < 0.001), acute cellular rejection ( P = 0.002), and sepsis ( P = 0.007) were significantly lower in the Spx group. Graft survival of the Spx group was significantly better than that of the no-Spx group ( P < 0.001; hazard ratio [HR], 1.788; 95% confidence interval, 1.214-2.431). A multivariate analysis revealed that 3 variables, platelet count ≤4.0 × 10 4 /mm 3 ( P = 0.029; HR, 2.873), donor age ≥60 y old ( P = 0.013; HR, 6.693), and portal venous pressure at closure ≥20 mm Hg ( P = 0.010; HR, 3.891), were independent predictors of graft loss within 6 mo after simultaneous Spx during LDLT. Spx is a safe inflow modulation procedure with a positive impact on both postoperative complications and prognosis for most patients. However, patients with the 3 aforementioned independent factors could experience graft loss after LDLT.

Clinical Impact and Risk Factors of Seizure After Liver Transplantation: A Nested Case-Control Study.

Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23kg/m2, donor age ≥45years, intraoperative continuous renal replacement therapy and delta sodium level ≥4mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome.

The BAR Score Predicts and Stratifies Outcomes Following Liver Retransplantation: Insights From a Retrospective Cohort Study.

Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575-10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.

Ellipro scores of donor epitope specific HLA antibodies are not associated with kidney graft survival.

In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants.

Missed Diagnosis as Risk Factor for Graft Loss: Analysis of the Tuscany Kidney Transplant Waitlist

Missed Diagnosis as Risk Factor for Graft Loss: Analysis of the Tuscany Kidney Transplant Waitlist

Effect of Early Enteral Nutrition on Graft Loss After Living Donor Liver Transplantation: A Propensity Score Matching Analysis

This study aimed to elucidate the effect of early enteral nutrition on graft loss within 12 h after living-donor liver transplantation (LDLT) using propensity score-matching analysis and subsequently examine the risk factors for graft loss after LDLT. We retrospectively reviewed the data of 467 LDLT patients who were assigned to the early and non-early groups based on the optimal cutoff value of 12 h for the starting time of early enteral nutrition after LDLT to predict graft loss. The 1-year graft survival rate of the early group before propensity score-matching was 92.1%, whereas the 1-year graft survival rate of the non-early group was 86.2%. There was no significant difference between the 2 groups (P=.067). The incidences of early allograft dysfunction (EAD), small-for-size graft (SFSG) syndrome, acute cellular rejection (ACR), and sepsis were not statistically different between the 2 groups (P=.12, .91, .46, and .056, respectively). After propensity score-matching, the 1-year graft survival rate of the early group was 94.4%, whereas the 1-year graft survival rate of the non-early group was 85.4% (P=.034). The incidences of EAD, SFSG syndrome, and ACR were not statistically different between the 2 groups (P=.43, .81, and .24, respectively). However, the incidence of sepsis was statistically different between the 2 groups (non-early: 10.7% vs early: 3.6%, P=.038). Early enteral nutrition within 12 h after LDLT may contribute to better graft survival in LDLT patients by preventing sepsis.

Outcomes and Risk Factors for Liver Transplantation Using Graft-to-Recipient Weight Ratio Less Than 0.8 Graft From Living Donors: Multicentric Cohort Study.

To compare graft survival after living donor liver transplantation (LDLT) in patients receiving graft-to-recipient weight ratio (GRWR) <0.8 versus GRWR≥0.8 grafts and identify risk factors for graft loss using GRWR<0.8 grafts. Favorable outcomes after LDLT using GRWR<0.8 grafts were recently reported; however, these results have not been validated using multicenter data. This multicentric cohort study included 3450 LDLT patients. Graft survival was compared between 1:3 propensity score-matched groups and evaluated using various Cox models in the entire population. Risk factors for graft loss with GRWR<0.8 versus GRWR≥0.8 grafts were explored within various subgroups using interaction analyses, and outcomes were stratified according to the number of risk factors. In total, 368 patients (10.7%) received GRWR<0.8 grafts (GRWR<0.8 group), whereas 3082 (89.3%) received GRWR≥0.8 grafts (GRWR≥0.8 group). The 5-year graft survival rate was significantly lower with GRWR<0.8 grafts than with GRWR≥0.8 grafts (85.2% vs 90.1%, P =0.013). Adjusted hazard ratio for graft loss using GRWR<0.8 grafts in the entire population was 1.66 (95% CI: 1.17-2.35, P =0.004). Risk factors exhibiting significant interactions with GRWR<0.8 for graft survival were age ≥60 years, Model for End-stage Liver Disease score ≥15, and male donor. When ≥2 risk factors were present, GRWR<0.8 grafts showed a higher risk of graft loss compared with GRWR≥0.8 graft in LDLT (hazard ratio 2.98, 95% CI: 1.79-4.88, P <0.001). GRWR<0.8 graft showed inferior graft survival than controls (85.2% vs 90.1%), especially when ≥2 risk factors for graft loss (among age 60 years or above, Model for End-stage Liver Disease score ≥15, or male donor) were present.

Preventing Rejection of the Kidney Transplant.

With increasing knowledge of immunologic factors and with the advent of potent immunosuppressive agents, the last several decades have seen significantly improved kidney allograft survival. However, despite overall improved short to medium-term allograft survival, long-term allograft outcomes remain unsatisfactory. A large body of literature implicates acute and chronic rejection as independent risk factors for graft loss. In this article, we review measures taken at various stages in the kidney transplant process to minimize the risk of rejection. In the pre-transplant phase, it is imperative to minimize the risk of sensitization, aim for better HLA matching including eplet matching and use desensitization in carefully selected high-risk patients. The peri-transplant phase involves strategies to minimize cold ischemia times, individualize induction immunosuppression and make all efforts for better HLA matching. In the post-transplant phase, the focus should move towards individualizing maintenance immunosuppression and using innovative strategies to increase compliance. Acute rejection episodes are risk factors for significant graft injury and development of chronic rejection thus one should strive for early detection and aggressive treatment. Monitoring for DSA development, especially in high-risk populations, should be made part of transplant follow-up protocols. A host of new biomarkers are now commercially available, and these should be used for early detection of rejection, immunosuppression modulation, prevention of unnecessary biopsies and monitoring response to rejection treatment. There is a strong push needed for the development of new drugs, especially for the management of chronic or resistant rejections, to prolong graft survival. Prevention of rejection is key for the longevity of kidney allografts. This requires a multipronged approach and significant effort on the part of the recipients and transplant centers.

#5999 GRADES II-III INTRA-ABDOMINAL HYPERTENSION INCREASE THE RISK OF GRAFT LOSS OR DEATH AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Intra-abdominal hypertension (IAH) is common among post-surgical, critically ill and kidney transplant patients, and is associated with acute kidney injury and increased morbidity and mortality. We aimed to describe the medium-term effect of IAH on graft and patient survival after deceased-donor kidney transplantation. Method 192 consecutive patients who received a cadaveric renal allograft transplant at our hospital were included in this study. IAP was measured every 8h for at least the first 72h after surgery using the urinary bladder technique, and an average value was obtained. Patients were followed up for 24 months or until a composite outcome (defined as graft loss or recipient death) occurred. Clinical, anthropometric, and analytical data was extracted from our hospital's database. Statistical analysis was performed using IBM SPSS Statistics 22. The study was approved by the local ethics committee. Results 192 patients were included. Relevant clinical and anthropometric data are summarized in Table 1. Patients with grades II or III IAH were more frequently male, had longer dialysis vintage, received more frequently hemodialysis as renal replacement therapy and suffered delayed graft function, graft loss or death more repeatedly. In Kaplan-Meier analysis, grade II IAH or higher were associated with lower composite-outcome free survival (Log-Rank: 8.053; p = 0.018) (Figure 1). Conclusion Grade II-III IAH appear to be a risk factor for graft loss or recipient death in our sample of deceased donor kidney transplant recipients. Monitoring of intra-abdominal hypertension could provide useful information to identify patients at higher risk of post-transplant complications.

Long-term CMV monitoring and chronic rejection in renal transplant recipients.

Cytomegalovirus (CMV) is well established to be an independent risk factor for graft loss after kidney transplantation (KTx). Monitoring for CMV in the chronic phase is not defined in the current guideline. The effects of CMV infection, including asymptomatic CMV viremia, in the chronic phase are unclear. We performed a single-center retrospective study to investigate incidence of CMV infection in the chronic phase, defined as more than 1 year after KTx. We included 205 patients who received KTx between April 2004 and December 2017. The CMV pp65 antigenemia assays to detect CMV viremia were continuously performed every 1-3 months. The median duration of the follow-up was 80.6 (13.1-172.1) months. Asymptomatic CMV infection and CMV disease were observed in 30.7% and 2.9% in the chronic phase, respectively. We found that 10-20% of patients had CMV infections in each year after KTx which did not change over 10 years. The history of CMV infection in the early phase (within 1 year after KTx) and chronic rejection were significantly associated with CMV viremia in the chronic phase. CMV viremia in the chronic phase was significantly associated with graft loss. This is the first study to examine the incidence of CMV viremia for 10 years post KTx. Preventing latent CMV infection may decrease chronic rejection and graft loss after KTx.

Kidney Transplant: Survival Analysis and Prognostic Factors after 10 Years of Follow-Up

The aim of this work is to analyse recipient and graft survival after kidney transplant in a three-year cohort and to identify predictive factors with up to 10 years of follow-up. Methods: retrospective consecutive cohort study of 250 kidney transplant recipients operated between 2010 and 2012. Multiorganic transplants and both dead-donor and living-donor transplants were included. Data were collected from electronic health records. A survival analysis was conducted using the Kaplan-Meier method and a Cox proportional-hazards multivariate model. Results: mean follow-up was 8.1 ± 3.2 years. Graft survival at 2, 5 and 10 years was 89.0%, 85.1% and 78.4% respectively. The multivariate model identified the following risk factors for graft loss: diabetic nephropathy (HR 3.2 CI95% [1.1–9.4]), delayed graft function (3.8 [2.0–7.4]), chronic kidney rejection (3.7 [1.2–11.4]), and early surgical complications (2.6 [1.4–5.1]). Conversely, combined transplant was found to be a protective factor for graft loss (0.1 [0.0–0.5]). Recipient patient survival was 94.3%, 90.0% and 76.6% at 2, 5 and 10 years respectively. The model identified the following mortality risk factors: older recipient age (1.1 [1.1–1.2]), combined transplant (7.6 [1.7–34.5]) and opportunistic infections (2.6 [1.3–5.0]). Conclusions: 10-year recipient and graft survival were 76.6% and 78.4% respectively. Main mortality risk factors were older recipient age, opportunistic infections and multiorganic transplant. Main graft loss risk factors were diabetic nephropathy, delayed graft function, chronic kidney rejection and early surgical complications.

Clinical Outcomes in Living Donor Kidney Transplantation: A Single Center Experience in Latin America

In Latin America, few reports are available about the clinical outcomes of living donor kidney transplants (LDKT). We aim to evaluate the main clinical outcomes for LDKT patients in a single center's experience. We retrospectively evaluated 530 LDKT patients who underwent transplantation from August 2008 to December 2020 at Colombiana de Trasplantes. Graft survival censored for death and patient survival were determined up to 5 years post-transplantation by the Kaplan-Meier method. Vascular and urinary complications, readmission, and reintervention rates were documented. A total of 530 LDKT patients were analyzed. Most of the recipients were men (56%). There were 123 patients (23.2%) with a preemptive transplant. Panel reactive antibody type I and II had higher immunologic risk (>20%) in 15.9% of the patients. The donor mean age was 37.8 ± 11.5 years. Most of the donors were women (52.6%) and related to the recipient (69.1%). Multivariate analysis identified panel reactive antibody type II (P=0.003), female donor (P=0.001), surgical reintervention at 30 days post-transplantation (P < .01), and delayed graft function (P < .01) as risk factors for graft loss. The graft survival death-censored rates were 93.7% and 89% at 1 and 5 years, respectively. Patient survival rates were 97.0% and 94.1% at 1 and 5 years after transplantation, respectively. The long-term graft and patient survival rates in our center are comparable to previous reports from other leading centers. The clinical outcomes from a medium-sized center can be noteworthy, although not entirely new.

Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes

BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n=35 and high-level viremia, n=26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P=.002), age (OR, 1.047; 95% CI, 1.008-1.088; P=.018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P=.047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P=.004), and graft survival was lower in patients with BKVi and high-level viremia (P=.027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P=.029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P=.046) were predictors of shorter graft survival. BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

Snowflake epitope matching correlates with child-specific antibodies during pregnancy and donor-specific antibodies after kidney transplantation.

Development of donor-specific human leukocyte antigen (HLA) antibodies (DSA) remains a major risk factor for graft loss following organ transplantation, where DSA are directed towards patches on the three-dimensional structure of the respective organ donor's HLA proteins. Matching donors and recipients based on HLA epitopes appears beneficial for the avoidance of DSA. Defining surface epitopes however remains challenging and the concepts underlying their characterization are not fully understood. Based on our recently implemented computational deep learning pipeline to define HLA Class I protein-specific surface residues, we hypothesized a correlation between the number of HLA protein-specific solvent-accessible interlocus amino acid mismatches (arbitrarily called Snowflake) and the incidence of DSA. To validate our hypothesis, we considered two cohorts simultaneously. The kidney transplant cohort (KTC) considers 305 kidney-transplanted patients without DSA prior to transplantation. During the follow-up, HLA antibody screening was performed regularly to identify DSA. The pregnancy cohort (PC) considers 231 women without major sensitization events prior to pregnancy who gave live birth. Post-delivery serum was screened for HLA antibodies directed against the child's inherited paternal haplotype (CSA). Based on the involved individuals' HLA typings, the numbers of interlocus-mismatched antibody-verified eplets (AbvEPS), the T cell epitope PIRCHE-II model and Snowflake were calculated locus-specific (HLA-A, -B and -C), normalized and pooled. In both cohorts, Snowflake numbers were significantly elevated in recipients/mothers that developed DSA/CSA. Univariable regression revealed significant positive correlation between DSA/CSA and AbvEPS, PIRCHE-II and Snowflake. Snowflake numbers showed stronger correlation with numbers of AbvEPS compared to Snowflake numbers with PIRCHE-II. Our data shows correlation between Snowflake scores and the incidence of DSA after allo-immunization. Given both AbvEPS and Snowflake are B cell epitope models, their stronger correlation compared to PIRCHE-II and Snowflake appears plausible. Our data confirms that exploring solvent accessibility is a valuable approach for refining B cell epitope definitions.

The Immunohistochemical Expression of the Von Willebrand Factor: A Potential Tool to Predict Kidney Allograft Outcomes.

Few reports assessed endothelial activation biomarkers in kidney allograft biopsies using immunohistochemistry. This retrospective cohort study evaluated the association between posttransplant outcomes and the immunohistochemistry expression of Caveolin-1, Von Willebrand Factor (Vwf), and T-Cadherin in for-cause biopsies diagnosed as interstitial fibrosis and tubular atrophy of unknown etiology. Samples with antibody-mediated changes were excluded. The patients were followed for 3 years after the biopsy or until graft loss/death. Seventy-one (71) samples from 66 patients were included. Eighteen (25.4%) patients lost their grafts, mainly due to chronic rejection (33.3%). Caveolin-1 and T-Cadherin were not associated with graft loss. Vwf had good accuracy in predicting graft failure (AUC 0.637, 95% CI 0.486 to 0.788 P =0.101). The presence of more than 10% of Vwf positivity in the microvasculature (Vwf >10%) was associated with reduced death-censored graft survival (58.2% vs. 85.4% P =0.006), and this result was also observed in the subgroup presenting mild interstitial fibrosis (ci=1) (65.7% vs. 88.6% P =0.033). The multivariate analysis showed that Vwf >10% was an independent risk factor for graft loss (HR=2.88, 95% CI 1.03 to 8.02 P =0.043). In conclusion, Vwf might be an additional tool to predict allograft outcomes in kidney transplant recipients with interstitial fibrosis and tubular atrophy of unknown etiology, probably reflecting immune endothelial activation.

Long-term outcomes of kidney transplantation from expanded criteria donors with Chinese novel donation policy: donation after citizens’ death

IntroductionThe Chinese Government initiated the Donation after Citizens' Death policy in 2010. To now, it has been a major source of organs for transplant. Since it is still a young policy, corresponding clinical evidence is still urgently needed for its improvement. Compared to kidneys donated by SCD (standard criteria donor), increasing the use of ECD (expanded criteria donor) derived kidneys is a way to expand the donor pool but is also a result of the aging demography of China. This study is based on the data of kidney transplantation in our center with the Donation after Citizens' Death policy, aiming to provide a reference for the clinical use of ECD kidneys.MethodA retrospective study enrolled 415 kidney transplants derived from 211 donors performed between October 2011 and October 2019. A total of 311 (74.9%) organs were donated from 159 (75.4%) SCDs, and the remaining 104 (25.1%) were from 52 (24.6%) ECDs. The log-rank test was used to compare the difference in survival and postoperative complications. The Chi-square test was used to compare the occurrence of postoperative complications and postoperative renal function. The Cox regression analysis was used for risk factor screening.ResultAnalysis showed that grafts from ECD were poorer in survival (P = 0.013), while their recipients had comparable (P = 0.16) survival. Moreover, it also was an independent risk factor for graft loss (HR 2.27, P = 0.044). There were significantly more AR occurrences in the ECD group compared with SCD group (25.0% vs. 15.8%, P = 0.004), but no significant difference was found in infection (51.9% vs. 47.6%, P = 0.497) and DGF (26.0% vs. 21.9%, P = 0.419) between them. Similarly, fewer recipients in the ECD group were free from AR within 1 year after transplantation (P = 0.040), with no statistical difference in all-cause infection prevalence in 1 year (P = 0.168). The eGFR in the ECD group was significantly worse than that in the SCD group at 3 months, 6 months, 1 year, 3 years, and the highest value posttransplant (all < 0.05), but no difference at 5 years posttransplant. Besides, results showed cardiac arrest (uncontrolled vs. controlled, HR 2.49, P = 0.049), HLA mismatch (4–6 loci vs. 0–3 loci, HR 3.61, P = 0.039), and AR occurrence (HR 2.91, P = 0.006) were demonstrated to be independent risk factors for graft loss.ConclusionThe ECD-derived kidney was worse than the SCD-derived kidney in terms of graft survival and AR occurrence, and trend to an inferior renal function postoperative. However, the recipient survival, DGF occurrence, and all-cause infection occurrence were similar.