Abstract Kidney transplantation is the treatment of choice for patients with end stage renal disease to optimize survival, freedom from morbidity and quality of life. A fundamental aspect of the ...pre-transplant assessment is a thorough understanding of their immunological history and prior exposures, so that the immunological risk from a given donor can be estimated, if not quantified, in order to guide interventions to optimize transplant access and success. The methodologies available to complete this assessment have evolved rapidly, with flow cytometric based analyses now standard in many laboratories, availability of comprehensive molecular methods for HLA typing of both donors and recipients, and an increasing recognition of the vital dialogue that must occur between the HLA laboratory and transplant clinicians. This review considers the pre-transplant assessment journey that a recipient undertakes, from initial referral to transplantation, discussing the methodologies used, benefits and limitations offered by current technologies, and reviews the basics of interpretation.
While there is increasing reliance on a negative virtual crossmatch to proceed with deceased donor kidney transplantation, a flow cytometry crossmatch (FCXM) is still usually performed after the ...transplant has already occurred. Our center has eliminated pretransplant physical crossmatches for most patients, and since 2018, we have eliminated the systematic performance of posttransplant FCXMs.
We studied all deceased donor kidney transplants in our program between June 1, 2018, and March 31, 2021, to evaluate the impact of eliminating retrospective FCXMs on resource utilization and graft outcomes (ie, the occurrence of antibody-mediated rejection AMR in the first 3-mo posttransplant).
A total of 358 kidney transplants occurred during the study period, and approximately 70% of these transplants proceeded without the performance of any FCXM. Incidence rates of AMR were low (9.63 per 1000 person-months), which compared favorably with the incidence rate of AMR during the 3-y period preceding the policy (4.82 per 1000 person-months,
= 0.21).
Our results suggest that moving away from retrospective FCXM and relying exclusively on the virtual crossmatch is safe and efficient for kidney allocation.
Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status.
Both peritubular capillary (PTC) C4d deposition and macrophage/monocyte (MO) infiltration ...in acute rejection (AR) have separately been shown to be associated with reduced graft survival and recently were demonstrated to be closely correlated in AR. Whether MO infiltration is an independent predictor of graft outcome is uncertain.
All patients with biopsy-proven AR (over a 3-year period) were included (N = 96). All biopsies (N = 121) were graded according to the Banff 97 criteria and immunohistochemically stained for C4d and MO (CD68). The primary outcome was glomerular filtration rate (GFR) <30 mL/min 1-year posttransplant as estimated by the Modified Diet in Renal Disease (MDRD) Formula. Secondary outcomes at 2 and 4 years' posttransplant were also explored. A variety of clinical and biopsy variables were statistically analyzed to establish univariate predictors of graft outcome. Stepwise multivariate logistic regression modeling was applied to determine independent predictors of outcomes.
There was a close correlation between PTC C4d and glomerular MO infiltration (P < 0.001). Univariate predictors of primary outcome (GFR <30 mL/min 1-year posttransplant) included mean glomerular MO count ≥1.0 MO/glomerulus (P = 0.014), female sex (P = 0.02), higher peak (P = 0.005), and pretransplant (P = 0.003) panel-reactive antibody levels, cadaveric donor (P = 0.006), transplant glomerulitis (P = 0.004), and longer cold ischemic time (CIT) (P = 0.002). Mean MO/glomerulus ≥1.0 OR 10.3 (1.23, 87.1), female sex OR 5.27(1.31, 21.1), and CIT OR 1.14 (1.06, 1.25) were identified as independent predictors of adverse graft outcome. Furthermore, mean MO/glomerulus ≥1.0 independently predicted poor renal function at 2 years OR 3.89 (1.19, 12.70) and 4 years OR 4.03 (1.22, 13.28) posttransplant.
The results demonstrate that glomerular MO infiltration is an independent predictor of worse outcomes posttransplant following acute renal allograft rejection.
To report outcomes of keratolimbal allograft (KLAL) compatible for both human leukocyte (HLA) and/or blood type using oral prednisone, mycophenolate, and tacrolimus, with basiliximab if panel ...reactive antibodies (PRA) are present. Intravenous immunoglobulin (IVIG) was used post-operatively if donor-specific anti-HLA antibodies (DSA) were present.
Retrospective interventional series of consecutive patients with KLAL for limbal stem cell deficiency (LSCD) from HLA and/or blood type compatible deceased donors with a minimum follow-up time of 12 months. Main outcome measures were ocular surface stability, visual acuity and systemic immunosuppression (SI) adverse events.
Eight eyes of eight patients with mean age of 48.6 ± 10.1 years (range 34–65 years) were included. Mean follow-up time was 37.3 ± 22.7 months (range 12–71 months) following KLAL; four (50%) had combined LR-CLAL surgery. The etiologies of LSCD were Stevens-Johnson Syndrome (n = 4/8), aniridia (n = 2/8), chemical injury (n = 1/8) and atopic eye disease (n = 1/8). All patients had PRA present and received basiliximab infusions. 5/8 patients received IVIG based on DSA identified pre-operatively. At last follow-up, 7 eyes (87.5%) had a stable ocular surface; 1 eye (12.5%) developed failure and had keratoprosthesis implantation. There was a significant improvement in visual acuity from 1.65 ± 0.48 to 0.68 ± 0.34 logMAR (p = 0.01). SI was tolerated well with minimal adverse events.
Preliminary outcomes of KLAL with ABO compatible tissue using the Cincinnati protocol, preoperative basiliximab (when PRA present) and post-operative IVIG (when DSA present) are encouraging. This protocol may allow for utilization of deceased donor tissue with results approximating those of living donor tissue transplanted for severe bilateral LSCD.
This review describes the utility and limitations of measure for assessing the presence, relative strength, and clinical impact of human leukocyte antigen (HLA) alloantibodies, as well as the other ...qualitative features of antibodies that are important considerations in assessing patient risk.
Using MFI as a measure of antibody amount is limited for a variety of reasons. Standardized serum manipulations such as ethylene-diamine-tetra-acetic acid treatment or serum dilution results in better definition of relationships between MFI and antibody titer or complement activation, toward greater alignment in defining positivity. Increased understanding of HLA epitopes has improved the ability to precisely define donor specific HLA antibody (DSA) specificities and the analysis of structural HLA Class II epitope mismatches in donor-recipient pairs may assist in the prevention of de novo DSA development. Studies of antibody isotypes and immunopathological mechanisms underlying graft injury mediated by non-HLA antibodies are expanding the assessemnt of immunological risk.
Careful analysis of both semiquantitative and qualitative properties of donor-specific antibodies continues to improve our ability to study the effects of DSA on clinical outcomes in solid organ transplantation.
Background
It is estimated that 25%‐35% of heart transplant recipients develop de novo donor‐specific antibodies (dnDSA). One factor that appears to play a role in clinical outcomes is DSA ...persistence. The objective of this study was to determine the incidence of transient and persistent dnDSA in a Canadian heart transplant population and to evaluate their impact on coronary allograft vasculopathy (CAV), graft function, and mortality.
Methods
A retrospective study of consecutive adult and transitioned pediatric heart transplant recipients (2008‐2015) in Toronto was performed. Clinical demographics were collected prospectively. HLA antibody testing was performed using Luminex single antigen assays. In statistical analysis, dnDSA was modeled as a time dependent covariate.
Results
During a median follow‐up of 4.1 years, dnDSA were detected in 42 (23%) with a median time to detection of 329 days (156‐740); 27 (64%) developed persistent dnDSA. Persistent dnDSA conferred an increased risk of death with a HR 4.0 (95%CI 1.4‐12.1) when adjusted recipient age, CAV, and cytomegalovirus status.
Conclusions
Transient dnDSA were not associated with adverse outcomes after heart transplantation. This suggests that transient dnDSA may not require enhanced immunosuppression, increased HLA antibody monitoring, or additional physiological assessment. By knowing the transient dnDSA status, clinicians may minimize both recipient morbidity and cost without increasing harm.
Background The link between delayed graft function (DGF) and death with graft function (DWGF) in living donor kidney transplant recipients presently is unknown. Study Design Retrospective cohort ...study. Setting & Participants 44,630 adult living donor kidney recipients (first transplants only) in the US Renal Data System from January 1, 1994, to December 31, 2004. Predictor DGF, defined as the need for dialysis therapy in the first week after transplant. Outcome Time to DWGF. Measurements Kaplan-Meier curves were constructed to assess the impact of DGF on DWGF. Recipients with DGF were 1:1 propensity score matched to those without DGF, and time-dependent Cox proportional hazards models were used to examine factors associated with DWGF. Subgroup and sensitivity analyses also were conducted. Results DWGF occurred in 3,878 patients during 3.9 years' (median) follow-up. In patients with DGF, survival with graft function at 1, 3, 5, and 10 years was 91.9%, 86.8%, 81.6%, and 61.7%, respectively (in patients without DGF, these values were 98.0%, 95.2%, 91.6%, and 80.1%, respectively; P < 0.001 compared with the DGF group). In a fully adjusted time-dependent Cox model, HRs for DWGF in patients with DGF (vs without DGF) were 6.55 (95% CI, 4.78-8.97), 3.55 (95% CI, 2.46-5.11), 2.07 (95% CI, 1.53-2.81), and 1.48 (95% CI, 1.26-1.73) at 0-1, 1-3, 3-12, and longer than 12 months posttransplant, respectively. Propensity score analysis showed similar results. Inferences were unchanged after adjustment for kidney function and acute rejection at 6 months and 1 year posttransplant. Cardiovascular and infectious causes of DWGF were more prevalent in patients with DGF. The association was more marked in female recipients and robust to various sensitivity analyses. Limitations The impact of lesser decreases in early graft function could not be evaluated. Conclusions DGF is associated with an increased risk of DWGF in living donor kidney recipients. The mechanisms underlying this relation require further study.
Background
The number of solid organ transplants in Canada has increased 33% over the past decade. Hospital readmissions are common within the first year after transplant and are linked to increased ...morbidity and mortality. Nearly half of these admissions to the hospital appear to be preventable. Mobile health (mHealth) technologies hold promise to reduce admission to the hospital and improve patient outcomes, as they allow real-time monitoring and timely clinical intervention.
Objective
This study aims to determine whether an innovative mHealth intervention can reduce hospital readmission and unscheduled visits to the emergency department or transplant clinic. Our second objective is to assess the use of clinical and continuous ambulatory physiologic data to develop machine learning algorithms to predict the risk of infection, organ rejection, and early mortality in adult heart, kidney, and liver transplant recipients.
Methods
Remote Mobile Outpatient Monitoring in Transplant (Reboot) 2.0 is a two-phased single-center study to be conducted at the University Health Network in Toronto, Canada. Phase one will consist of a 1-year concealed randomized controlled trial of 400 adult heart, kidney, and liver transplant recipients. Participants will be randomized to receive either personalized communication using an mHealth app in addition to standard of care phone communication (intervention group) or standard of care communication only (control group). In phase two, the prior collected data set will be used to develop machine learning algorithms to identify early markers of rejection, infection, and graft dysfunction posttransplantation. The primary outcome will be a composite of any unscheduled hospital admission, visits to the emergency department or transplant clinic, following discharge from the index admission. Secondary outcomes will include patient-reported outcomes using validated self-administered questionnaires, 1-year graft survival rate, 1-year patient survival rate, and the number of standard of care phone voice messages.
Results
At the time of this paper’s completion, no results are available.
Conclusions
Building from previous work, this project will aim to leverage an innovative mHealth app to improve outcomes and reduce hospital readmission in adult solid organ transplant recipients. Additionally, the development of machine learning algorithms to better predict adverse health outcomes will allow for personalized medicine to tailor clinician-patient interactions and mitigate the health care burden of a growing patient population.
Trial Registration
ClinicalTrials.gov NCT04721288; https://www.clinicaltrials.gov/ct2/show/NCT04721288
International Registered Report Identifier (IRRID)
PRR1-10.2196/26816
New data suggest that among kidney transplant recipients, those whose serum contains donor-specific antibodies that bind C1q fare the worst. Although these findings are intriguing, several unanswered ...questions remain and changing practice to include a C1q binding assay as standard of care in kidney transplantation would be premature.
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