Kidney Transplant Outcomes Research Articles

Natural Killer Cell Phenotypes and Clinical Outcomes in Pediatric Kidney Transplantation.

Natural killer (NK) cells have gained recognition for playing an integral role in both alloimmunity and protective immunity, particularly viral infection control, in solid organ transplantation. Using data from the Clinical Trials in Organ Transplantation in Children (CTOTC) study entitled, "Immune Development in Pediatric Transplantation," (NCT00951353), we aimed to identify NK cell phenotypes that were associated with viral infection versus alloreactive events during the first year after transplantation. We also examined the relationship between NK cells with 7-year patient and allograft survival using the Scientific Registry for Transplant Recipients (SRTR) database. A secondary analysis of peripheral blood mononuclear cells from 98 children aged 1-20 years old with kidney transplants was conducted using multiparameter flow cytometry for the following NK cell phenotypes: CD56bright, CD56dim, and CD56negative. We associated these phenotypes with either viral infection or alloimmunity (de novo donor-specific antibody (dnDSA) development or acute rejection), using Fine-Gray subdistribution hazard models for competing risks. Secondary outcomes included allograft and patient survival. We demonstrated that specific baseline NK cell phenotypes obtained prior to transplantation may be associated with either viral infection or alloimmunity. An elevation in CD56dim frequency was associated with an increased risk of infection, while an increase in CD56negative absolute count was associated with an increased risk of an alloimmune event. NK cells were not associated with graft survival. NK cell phenotyping may be a useful tool to help differentiate infectious from alloimmune risk.

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy.

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

Acute Kidney Injury in Deceased Organ Donors: Risk Factors And Impacts on Transplantation Outcomes

Background. Acute kidney injury in deceased donors (D-AKI) is one of the common causes of donor kidney discard. The risk factors for D-AKI and its impact on kidney transplantation outcomes are not yet fully understood. Methods. This single-center, retrospective cohort study included 388 donors referred between June 2021 and December 2022. D-AKI was defined and staged according to kidney disease: Improving global outcomes criteria, and donor clinical variables were analyzed to identify risk factors for D-AKI. Delayed graft function and estimated glomerular filtration rate (eGFR) at 6 mo were evaluated in 369 kidney grafts transplanted from donors with and without D-AKI. Results. AKI was present in 171 deceased donors (44.1%), with 117 (30.2%) classified as AKI stage 1 and 54 (14%) as AKI stages 2 or 3. Donor history of hypertension (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.21-3.10; P = 0.005), history of diabetes (OR 2.2; 95% CI, 1.21-3.98; P = 0.008), and anoxia as the cause of death (OR 2.61; 95% CI, 1.5-4.61; P < 0.001) were independently associated with an increased risk of D-AKI. Multivariable mixed models identified donor age (β –0.49; 95% CI, –0.71 to –0.28; P < 0.001) as the only independent risk factor for lower eGFR at 6 mo. D-AKI was not associated with delayed graft function or lower eGFR at 6 mo. Conclusions. Hypertension, diabetes, and anoxia as the cause of death were identified as risk factors for AKI in deceased donors. D-AKI should not be used as the sole criterion to assess the risk of poor graft outcomes. A broader range of donor variables should be considered when evaluating graft viability.

A comparative study on outcomes of ABO-incompatible kidney transplants between robot-assisted vs. open surgery-propensity score-matched analysis: a retrospective cohort study.

Robot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi). This retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed. After PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15ml/min/1.73m², OKT: 64.53ml/min/1.73m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180-4.096, p = 0.848). RAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT's viability for high-risk kidney transplant recipients. The clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008|| https://www. gov/ ).

Association of variabilities in body mass index and metabolic parameters with post-kidney transplantation renal outcomes

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients.

Clinical characteristics and outcomes of kidney transplantation in autosomal dominant polycystic kidney disease patients.

Kidney transplantation (KT) is the best kidney replacementtreatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients. We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identifyprognostic factors influencing outcomes in ADPKD. Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group. ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.

Non-HLA Autoantibodies Against Angiotensin II Receptor 1 (AT1R) and Endothelin A Receptor (ETAR) in Pediatric Kidney Transplantation.

Antibody-mediated rejection (AMR) is the leading cause of premature kidney transplant failure. The role of alloantibodies against Human Leukocyte Antigens (HLA) has been a primary focus in AMR. More recently autoantibodies and alloantibodies against the angiotensin II receptor type 1 (AT1R) and the endothelin A receptor (ETAR) have been linked to poor allograft outcomes in kidney transplantation. Nevertheless, evidence supporting routine testing remains insufficient. ELISA testing for anti-AT1R and anti-ETAR antibodies was performed in a pediatric renal transplant cohort. We selected 12 pediatric recipients who had undergone protocol biopsies and antibody measurements at 6 and 24 months post-transplant. Immunohistochemistry was performed on biopsies for AT1R and ETAR as well as the adhesion molecules ICAM-1 and VCAM-1. The analysis showed that ICAM-1 and VCAM-1 expression was significantly increased, along with the presence of circulating antibodies, in patients at 24 months post-transplant compared to patients without circulating antibodies. The presence of anti-AT1R and anti-ETAR antibodies does not seem to influence the expression of their receptors in the transplanted organ. Instead, the increase in adhesion molecules may precede the development of histological damage. Therefore, enlarging the cohort and extending long-term observation would help to understand the impact of anti-AT1R and anti-ETAR antibodies after transplantation.

Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients

BackgroundDe novo donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response. MethodsData of 105 adult living-donor KT recipients were retrospectively assessed. ResultsOf the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT. ConclusionsPIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.

Geographic variation in kidney failure and transplantation in Aotearoa New Zealand: A population-based data linkage study.

This study aimed to describe the epidemiology of kidney replacement therapy (KRT) in Aotearoa New Zealand and assess the impact of residential location on access to kidney transplantation. AcceSS and Equity in Transplantation (ASSET), a health-linked data platform, was used to identify people commencing KRT in New Zealand from 2006 to 2019 and analyse regional epidemiology. Health services were classified as 'transplanting', 'intermediate' or 'remote' depending on their degree of separation from a transplant centre. Multiple logistic regression modelling was used to assess the predictors of deceased donor waitlisting or living donor transplantation within 6 months after starting KRT. Web-based mapping software was used to develop interactive geospatial maps. The cohort was 7704 people newly starting KRT. Living in an intermediate [odds ratio (OR): 0.73 (95% confidence interval (CI): 0.61-0.88)] or remote [OR: 0.38 (95% CI: 0.27-0.54)) region and Māori (OR: 0.35 (95% CI: 0.28-0.44)], Pacific [OR: 0.32 (95% CI: 0.24-0.42)) and Asian (OR: 0.66 (95% CI: 0.50-0.87)] ethnicity were associated with a decreased likelihood of timely waitlisting or transplantation. Regional maps can be explored here. There is marked geospatial and ethnic variation in the epidemiology of kidney failure and access to kidney transplantation across New Zealand. Geospatial mapping of kidney failure epidemiology and transplantation outcomes can provide opportunities to direct resources towards populations at greatest need.

Improved survival prediction for kidney transplant outcomes using artificial intelligence-based models: development of the UK Deceased Donor Kidney Transplant Outcome Prediction (UK-DTOP) Tool

The UK Deceased Donor Kidney Transplant Outcome Prediction (UK-DTOP) Tool, developed using advanced artificial intelligence (AI), significantly enhances the prediction of outcomes for deceased-donor kidney transplants in the UK. This study analyzed data from the UK Transplant Registry (UKTR), including 29,713 transplant cases between 2008 and 2022, to assess the predictive performance of three machine learning models: XGBoost, Random Survival Forest, and Optimal Decision Tree. Among these, XGBoost demonstrated exceptional performance with the highest concordance index of 0.74 and an area under the curve (AUC) consistently above 0.73, indicating robust discriminative ability and calibration. In comparison to the traditional Kidney Donor Risk Index (KDRI), which achieved a lower concordance index of 0.57, the UK-DTOP model marked a significant improvement, underscoring its superior predictive accuracy. The advanced capabilities of the XGBoost model were further highlighted through calibration assessments using the Integrated Brier Score (IBS), showing a score of 0.14, indicative of precise survival probability predictions. Additionally, unsupervised learning via k-means clustering was employed to identify five distinct clusters based on donor and transplant characteristics, uncovering nuanced insights into graft survival outcomes. These clusters were further analyzed using Bayesian Cox regression, which confirmed significant survival outcome variations across the clusters, thereby validating the model’s effectiveness in enhancing risk stratification. The UK-DTOP tool offers a comprehensive decision-support system that significantly refines pre-transplant decision-making. The study’s findings advocate for the adoption of AI-enhanced tools in healthcare systems to optimize organ matching and transplant success, potentially guiding future developments in global transplant practices.

Impact of deceased-donor characteristics on early graft function: outcome of kidney donor pairs accepted for transplantation.

The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals. This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure. The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors. Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics.

Impact of Donor-Recipient Relationship on Long-Term Outcomes in Living-Related Donor Kidney Transplantation.

BACKGROUND This study aimed to evaluate the impact of the donor-recipient relationship on the long-term outcomes of living-related kidney transplantation (LRKT), a topic that has been previously underreported. MATERIAL AND METHODS A total of 598 LRKTs performed between 2001 and 2021were analyzed and classified into 5 groups based on the donor-recipient relationship: 228 from mothers (M-to-C), 160 from fathers (F-to-C), 115 from siblings, 55 from spouses, and 40 from offspring. Graft survival, postoperative complications within the first year, serum creatinine (Scr), and hazard ratio (HR) for all-cause graft loss were assessed. RESULTS The overall 1-, 3-, 5-, 7-, and 10-year graft survival rates were 96.0%, 92.4%, 86.4%, 79.9%, and 69.9%, respectively. The graft survival rate in the sibling group was slightly higher than those in the M-to-C and F-to-C groups, and the differences between the groups were insignificant. The survival rates of grafts donated by spouses and offspring were lower than in other groups, and the incidence of graft loss within the first postoperative year was higher in the offspring group. In comparison to the sibling group, spouse and offspring donations increased the graft loss risk (HR, 3.3; 95% CI, 1.6-6.9) and 3.8 (1.7-8.4), respectively, followed by M-to-C and F-to-C donations (HR, 1.9; 95% CI: 1.2-3.4) and 1.8 (1.1-3.1), respectively, which were associated with elevated postoperative Scr levels. CONCLUSIONS Spouse and offspring donations significantly increased the risk of graft loss compared to donations from siblings, followed by M-to-C and F-to-C pairings, which were associated with higher postoperative Scr levels.

Assessing the reliability of rapid frozen tissue sections from pre-transplant kidney biopsies in DCD donors and correlations with clinico-pathological data: a pilot study.

Compared to donations after brain death, donations after circulatory death present a series of difficulties: the acquisition of the family's consent, the need for qualified personnel and specific resources, death assessment, assessment of the organ, and graft care (pre- and post-transplant). These are all time-related factors that negatively impact the organ, resulting in increased tubular, glomerular, and vascular damage. The evaluation of the organ, as per today's standards, requires three hours for the preparation and processing of formalin-fixed paraffin-embedded (FFPE) samples. An alternative to this is the use of the extemporaneous frozen biopsy. However, frozen samples are considered a second choice in the decision-making process. This retrospective study investigates the reliability of the frozen samples in identifying a series of morphological alterations compared to the more accepted results from FFPE samples. Additionally, two important clinical data, terminal serum creatinine levels and warm ischemia time, were correlated to the presence of some morphological alterations in an attempt to find effective and fast strategies to predict the kidney transplant outcome.

Outcomes of kidney transplantation in recipients with SARS-cov-2 infection: a 282-case single-center experience in Japan.

The coronavirus disease 2019, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a global epidemic. There are concerns regarding the severity of SARS-CoV-2 infections in kidney transplant (KTx) recipients. However, there is limited data on how the epidemic has affected the treatment and prognosis of these patients. Therefore, we aimed to report the changes in the treatment and outcomes of KTx recipients infected with SARS-CoV-2 during each wave at our institution. A total of 282 KTx recipients who were infected with SARS-CoV-2 during the study period were followed up at Tokyo Women's Medical University between March 2020 and August 2022. We investigated the outcomes and treatments of infected KTx recipients. Nineteen (6.7%) patients showed severe outcomes, including eight SARS-CoV-2 infection-related deaths. Risk factors associated with severe outcomes included underlying conditions, such as diabetes mellitus, heart disease, and liver disease (odds ratios, 2.09, 2.88, and 5.52, respectively). Treatment strategies changed throughout the epidemic in response to changes in the SARS-CoV-2 variants. Antiviral drugs were gradually administered as soon as they were approved for use. Treatment strategies for KTx recipients were gradually established over the course of the epidemic. Although the proportion of infected KTx recipients decreased compared to that of the general population throughout the epidemic, many patients still followed a severe course.

Clinical Characteristics and Outcomes of Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease

Clinical Characteristics and Outcomes of Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease

Outcomes of Kidney Transplantation from Deceased Diabetic Donors

Outcomes of Kidney Transplantation from Deceased Diabetic Donors

Impact of Probiotic Supplementation on Kidney Transplantation Outcomes

Impact of Probiotic Supplementation on Kidney Transplantation Outcomes

Impact of Delayed Graft Function on Kidney Transplant Outcomes

Impact of Delayed Graft Function on Kidney Transplant Outcomes

Kidney Transplant Outcomes in Patients with BMI of 35 or Greater: Should We Be Doing More? A Single-Center Experience

Kidney Transplant Outcomes in Patients with BMI of 35 or Greater: Should We Be Doing More? A Single-Center Experience

Kidney Transplantation Outcomes by Dialysis Modality in an Underserved Population

Kidney Transplantation Outcomes by Dialysis Modality in an Underserved Population