The transformative potential of artificial intelligence in solid organ transplantation.

Solid organ transplantation confronts numerous challenges ranging from donor organ shortage to post-transplant complications. Here, we provide an overview of the latest attempts to address some of these challenges using artificial intelligence (AI). We delve into the application of machine learning in pretransplant evaluation, predicting transplant rejection, and post-operative patient outcomes.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.

Regulatory B Cells in Solid Organ Transplantation: From Immune Monitoring to Immunotherapy.

Regulatory B cells (Breg) modulate the immune response in diverse disease settings including transplantation. Despite the lack of a specific phenotypic marker or transcription factor, their significance in transplantation is underscored by their ability to prolong experimental allograft survival, the possibility for their clinical use as immune monitoring tools, and the exciting prospect for them to form the basis for cell therapy. Interleukin (IL)-10 expression remains the most widely used marker for Breg.

Transitional B cell cytokines risk stratify early borderline rejection after renal transplantation.

Borderline rejection (BL) in renal transplantation is associated with decreased allograft survival, yet many patients with BL maintain stable graft function. Identifying patients with early BL at risk for shortened allograft survival would allow for timely targeted therapeutic intervention aimed at improving outcomes. 851/1187 patients transplanted between 2013-18 underwent early biopsy (0-4 mos).

Regulatory and transitional B cells: potential biomarkers and therapeutic targets in organ transplantation.

Purpose Of The Review: Regulatory B cells (Bregs) play a prominent role in various disease settings. While progress has been hindered by the lack of a specific Breg marker, new findings highlight their role modulating the alloimmune response and promoting allograft survival.

Recent Findings: Herein, we focus on the recent advances in Breg biology and their role in transplantation.

Antigen-specific B cells in kidney transplantation.

In this issue, Burton et al. describe a convincing method to identify and enumerate human leukocyte antigen-specific B cells and subsets using biotinylated human leukocyte antigen proteins. Importantly, they demonstrate that these antigen-specific B cells are found at a greater frequency in sensitized kidney transplant recipients when compared with healthy volunteers.

Transitional B cell cytokines predict renal allograft outcomes.

Early immunological biomarkers that predict rejection and chronic allograft loss are needed to inform preemptive therapy and improve long-term outcomes. Here, we prospectively examined the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNFα) produced by transitional-1 B cells (T1B) 3 months after transplantation as a predictive biomarker for clinical and subclinical renal allograft rejection and subsequent clinical course. In both Training ( = 162) and Internal Validation ( = 82) Sets, the T1B IL-10/TNFα ratio 3 months after transplantation predicted both clinical and subclinical rejection anytime in the first year.

Regulatory B cells: TIM-1, transplant tolerance, and rejection.

Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL-10 expression, but also utilizes additional regulatory mechanisms such as TGF-β, FasL, IL-35, and TIGIT.

Antigen-dependent interactions between regulatory B cells and T cells at the T:B border inhibit subsequent T cell interactions with DCs.

IL-10+ regulatory B cells (Bregs) inhibit immune responses in various settings. While Bregs appear to inhibit inflammatory cytokine expression by CD4+ T cells and innate immune cells, their reported impact on CD8+ T cells is contradictory. Moreover, it remains unclear which effects of Bregs are direct versus indirect.

Post-transplant donor specific antibody is associated with poor kidney transplant outcomes only when combined with both T-cell-mediated rejection and non-adherence.

Post-transplant donor specific antibody (DSA) is associated with poor renal allograft outcomes. However, variable timing of DSA assessment and inclusion of patients who undergo desensitization treatments have hindered our understanding of its consequences and limited its predictive value. Here we prospectively studied non-desensitized patients to determine factors associated with poor four-year outcomes in patients who developed post-transplant DSA.

High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss.

Background: High calcineurin inhibitor (CNI) intrapatient variability (IPV) has been associated with poor kidney allograft outcomes. However, the relationship between early allograft histological changes, their progression, and CNI-IPV is less well studied. Hence, we evaluated effect of CNI-IPV defined by the degree of fluctuation of CNI levels in all kidney transplant patients over 2 to 12 months posttransplant on early allograft inflammation, subsequent chronicity, and later clinical outcomes.

Regulatory and Effector B Cells: A New Path Toward Biomarkers and Therapeutic Targets to Improve Transplant Outcomes?

B cells shape the alloimmune response through polarized subsets. These cells inhibit or promote immune responses by expressing suppressive or proinflammatory cytokines. Their summed activity dictates the influence of B cells on the alloimmune response.

Regulatory B cells and transplantation: almost prime time?

Purpose Of Review: Regulatory B cells (Bregs) are potent inhibitors of the immune system with the capacity to suppress autoimmune and alloimmune responses. Murine transplant models showing that Bregs can promote allograft tolerance are now supported by clinical data showing that patients who develop operational tolerance have higher frequency of Bregs. Breg function has been widely studied resulting in improved understanding of their biology and effector mechanisms.

Early allograft inflammation and scarring associate with graft dysfunction and poor outcomes in renal transplant recipients with delayed graft function: a prospective single center cohort study.

Early histological progression that associates with delayed graft function (DGF) and its relationship to graft outcomes is less well-understood. We systematically evaluated early acute and chronic histological changes associated with DGF through serial biopsies (protocol: 3 and 12 months; for-cause) and related them to graft outcomes. 56/294 (19.

Short-term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol.

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months posttransplant.

Reduced human transitional B cell T1/T2 ratio is associated with subsequent deterioration in renal allograft function.

Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold fall in estimated glomerular filtration rate). Transitional B cells can be divided into T1 and T2 subsets based on surface phenotype.

Kidney Transplant Survival: Transforming Early Post-Transplant Opportunities to Long-Term Success.

Substantial strides have been made in improving the short-term success after kidney transplantation. Although there has been some progress, there has not been a robust improvement with respect to long-term outcomes. However, there remain many potentially modifiable transplant-specific risks to long-term patient and graft survival.

Immunologic human renal allograft injury associates with an altered IL-10/TNF-α expression ratio in regulatory B cells.

Human B cells with immunoregulatory properties in vitro (Bregs) have been defined by the expression of IL-10 and are enriched in various B-cell subsets. However, proinflammatory cytokine expression in B-cell subsets is largely unexplored. We examined the cytokine profiles of human PBMCs and found that subsets of CD24(hi)CD38(hi) transitional B cells (TrBs), CD24(hi)CD27(+) memory B cells, and naïve B cells express IL-10 and the proinflammatory cytokine TNF-α simultaneously.

Predicting 5-year risk of kidney transplant failure: a prediction instrument using data available at 1 year posttransplantation.

Background: Accurate prediction of kidney transplant failure remains imperfect. The objective of this study was to develop and validate risk scores predicting 5-year transplant failure, based on data available 12 months posttransplantation.

Study Design: Development and then independent multicenter validation of risk scores predicting death-censored and overall transplant failure.

Alemtuzumab induction in renal transplantation permits safe steroid avoidance with tacrolimus monotherapy: a randomized controlled trial.

Background: The use of alemtuzumab as induction immunosuppression for renal transplantation introduces the possibility of long-term tacrolimus monotherapy, avoiding maintenance with both corticosteroids and mycophenolate mofetil (MMF).

Methods: We conducted a single-center, prospective, open-label, randomized controlled trial comparing two steroid avoidance regimens between December 2006 and November 2010. One hundred and sixteen adult patients were randomized to either basiliximab induction followed by tacrolimus and MMF maintenance or to alemtuzumab induction followed by tacrolimus monotherapy.

Early BK polyomavirus (BKV) reactivation in donor kidney is a risk factor for development of BKV-associated nephropathy.

The pathogenesis of BK polyomavirus (BKV) infection and associated nephropathy in renal transplant recipients is not clearly understood. To gain insight, urine and plasma samples were collected from 112 renal transplant recipients before and after transplantation and tested for the presence of BKV by polymerase chain reaction. Detection of BKV infection very early (ie, 5 days) after transplantation was identified as a risk factor for subsequent BKV viremia and BKV-associated nephropathy.

The outcomes of critically ill patients with acute kidney injury receiving renal replacement therapy.

Introduction: Acute kidney injury (AKI) is common among critically ill patients and associated with a high mortality. We report here on the outcomes of patients with AKI who received renal replacement therapy (RRT) on our intensive care unit (ICU). We were interested in which parameters measured at the time of ICU admission were predictive of mortality and the long term renal sequelae for these patients.