Death-censored Graft Survival Research Articles

Kidney transplantation in Icelandic patients, 2000–2019: are outcomes affected by low volume?

BackgroundIn Iceland, a small number of kidney transplants from living donors (LDs) are performed at Landspitali University Hospital (LUH) in Reykjavik, while deceased donor transplants have until recently invariably been carried out abroad. In this study, we evaluated the outcome of kidney transplantation in Icelandic patients.MethodsThis was a retrospective study that included all Icelandic residents who underwent kidney transplantation between 1 January 2000 and 31 December 2019. Data were obtained from the Icelandic End-Stage Kidney Disease Registry, medical records at LUH, and the Scandiatransplant database. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate from serum creatinine for recipients and donors aged >18 years, and the modified Schwartz equation for those aged ≤18 years. Survival was estimated using the Kaplan–Meier method, and the log-rank test was employed for group comparisons.ResultsA total of 229 kidney transplants in 221 patients were performed during the 20-year period, of which 135 (58.9%) were from LDs. Transplants carried out at LUH were 118 (51.5%), of which 116 were from LDs. During a median follow-up of 7.4 years (range 0.1–20), 27 (12.2%) patients died, 20 (74%) of whom had a functioning graft. One-year patient survival was 99.1% [95% confidence interval (CI), 97.9–100], 5-year survival was 95.7% (95% CI, 92.7–98.7), and 10-year survival was 87.7% (95% CI, 82.4–93.4). Death-censored graft survival was 98.3% (95% CI, 96.6–100), 96.8% (95% CI, 94.4–99.2), and 89.2% (95% CI, 84.1–94.7) at 1, 5, and 10 years, respectively.ConclusionsPatient and graft survival are comparable with those of large transplant centers, demonstrating the feasibility of running a quality kidney transplant program in a small nation in collaboration with a larger center abroad.

#2822 Can KDPI estimate long-term graft survival in a cohort of Portuguese patients?

Abstract Background and Aims The Kidney Donor Profile Index (KDPI) was introduced in the United States in 2014 to support clinicians' decision-making regarding the acceptance or decline of potential donors. In Portugal, there is no valid stratification score to assist physicians in accepting or declining an organ offer. Our study aims to characterize a cohort of Portuguese kidney transplant recipients and donors and evaluate the correlation between KDPI and long-term graft survival. The results are interpreted considering the nuances of the Portuguese allocation system, which favors an age-matched donor-recipient allocation. Method We conducted an observational single-center retrospective cohort study, which included patients who received a deceased donor kidney transplant at our unit between January 2013 and December 2015. We excluded patients for whom the donor KDPI index was unavailable for retrieval. Besides the KDPI index, we collected data regarding the receptor's demographic, clinical, and immunological characteristics, as well as graft and recipient survival. The primary outcome was death-censored survival, and follow-up ended on the 31st of December 2023. The secondary outcome was survival with a functioning graft. Survival estimates were obtained using Kaplan-Meier curves. We performed univariate and multivariate survival analysis with log-rank tests and Cox proportional-hazards regression models. Results We selected 364 deceased-donor kidney recipients and 212 kidney donors. The mean KDPI was 60% and 53.3% of donors were classified as expanded criteria. The kidney recipients were predominantly male (68.4%), with a mean age of 50.16 years and an average of 4 HLA mismatches. Median follow-up was 102 months. Considering recipient characteristics according to pre-defined KDPI strata (≤ 20%, 21-85%, > 85%), recipients from higher KDPI were significantly older, with a mean age of 40.6, 48.8, and 61.1 years, respectively (p < 0.001), and had a higher average body mass index (p = 0.041). There were no significant differences regarding the number of HLA mismatches (p = 0.624) or the proportion of hypersensitized patients (p = 0.253) between classes. During follow-up, 16.8% patients presented graft failure and 9.9% died with a functioning graft. Cumulative death-censored graft survival at 5, 8, and 10 years was 87.7%, 87.1%, and 84.4% respectively. The cumulative percentage of patients living with a functioning graft at 5, 8, and 10 years was 83.6%, 76.7%, and 68.6%. Death-censored graft survival was lower in recipients of donors with higher KDPI (Fig. 1), although it did not reach statistical significance (p-value = 0.166). The number of HLA mismatches (p = 0.592) or the recipient's age (p = 0.513) did not significantly impact death-censored graft survival, whereas delayed graft function (DGF) was the variable with the strongest association in univariate analysis (p < 0.001). In a multivariate Cox regression model, KDPI (HR 1.02, p = 0.005) and DGF (HR 3.2, p < 0.001) correlated with graft loss, while older recipients (HR 0.971, p = 0.019) seemed to have a protective effect over death-censored survival. Patient survival with a functioning graft was significantly associated with KDPI strata (p = 0.008; Fig. 2), the recipient's age (p = 0.006), and DGF (p < 0.001) in univariate analysis. Considering KDPI kidneys ≥ 90%, 10-year cumulative death-censored survival was 67.9%. Conclusion In our sample, despite not reaching statistical significance, there was a trend for improved death-censored graft survival in patients with lower KDPI, which further emulates the results of other European cohorts. Nevertheless, the 10-year cumulative death-censored survival of higher KDPI kidneys (≥ 90%) was remarkable, showing that long-term acceptable outcomes can be achieved. The impact of KDPI on patient survival with a functioning graft is probably overestimated, given the bias introduced by the Portuguese matching system, which rewards an “old-for-old” donor-recipient allocation.

#2462 Impact of tacrolimus peak concentration on kidney graft outcomes

Abstract Background and Aims Low tacrolimus (Tac) trough concentration-to-dose ratio (C0/D ratio) identifies kidney transplant patients with high level of Tac metabolization and has been shown to be associated with lower graft function and survival. Why fast metabolizers experience poorer outcomes is however unclear. We hypothesized that fast metabolization is associated with higher maximal Tac blood concentration (Cmax) and that Tac Cmax has a detrimental effect by itself. Method We retrospectively selected consecutive kidney transplant patients who (I) were treated by Tac (irrespective of the pharmaceutical formulation), (ii) had systematic abbreviated pharmacokinetic tac evaluation at 3- and 12-months’ post-transplant, and (iii) had a minimal follow-up of 5 years. Fast metabolizers were defined by a C0/D ratio <1.05. Cmax was defined by the higher value of Tac concentration observed at 30, 90 or 180 minutes after Tac morning ingestion and was indexed to C0 in order to exclusively focus on patients with no obvious Tac overexposure. Association between Tac Cmax/C0 with traditional transplant outcomes was analysed by univariate and multivariate cox model and logrank test when appropriate. Results 436 patients transplanted from 2008 to 2016 (64% of male, mean age of 55 ± 13 y) with a median follow-up of 8 years (Q1: 6; Q3: 11) were analysed. Fast metabolizers had lower C0 while receiving higher dose of Tac and displayed significantly higher median Cmax (20 vs 17 μg/l, p < 0.001). Median Cmax/C0 was 3 and 2 in fast and non-fast metabolizers, respectively (p < 0.001). At 15 years’ post-transplant, death-censored graft survival was 13% lower for patients with the highest Cmax/C0 values (p = 0.04). In multivariate cox analysis, higher Cmax/C0 was independently associated with death-censored graft survival (HR = 1.30 (1.03;1.64), p = 0.026). Conclusion Our data support the hypotheses 1—that fast metabolizers exhibit higher Tac Cmax even in situations where Tac C0 are not elevated and 2—that exposure to high Cmax is a potential mechanism underlying their poorer outcome. Tac formulations prone to mitigate pharmacokinetic peak could thus be particularly beneficial to fast metabolizers and should be thoroughly evaluated in this indication.

#1985 Tocilizumab in chronic active antibody-mediated rejection: a randomized controlled open-label multi-center trial (INTERCEPT study)

Abstract Background and Aims Chronic active antibody mediated graft rejection (caAMR) caused by immune-mediated injury is the leading cause of long-term graft loss in kidney transplant recipients. Nevertheless, no effective treatment exists for caAMR to date, highlighting a great unmet need for evaluation of novel treatment options. Recently, tocilizumab (TCZ), a monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, by antagonizing IL-6-triggered inflammation and B cell/plasma cell-driven immune activation, has shown promise in the treatment of caAMR. However, TCZ has not been assessed systematically in a randomized study. The INTERCEPT study aims to evaluate the efficacy of addition of TCZ to standard of treatment (SOC) as compared to SOC alone in reducing the decline of graft function from baseline at 24 months after start of treatment as assessed by estimated glomerular filtration rate (eGFR) in kidney transplant recipients with caAMR. Method This ongoing randomized controlled open-label multi-center investigator-initiated trial plans to include a total of 50 adult kidney transplant recipients with biopsy-proven caAMR using Banff 2019 criteria at least 12 months after transplantation and eGFR ≥20 ml/min/1.73 m2. Any subject who underwent kidney transplantation in Sweden or is currently living in Sweden and being followed up at any of the Swedish transplant centers or their affiliated regional centers can be considered for participation. Participants are randomized to receive either TCZ (n=25) added to our standard of care (SOC) maintenance treatment or SOC alone (n=25) for a period of 24 months and followed for additional 12 months after cessation of the study medication. After the inclusion transplant biopsy at baseline, protocol biopsies are performed at 12 and 24 months. The study design flow-chart is shown in the Figure. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The eGFR is assessed using Modification of Diet in Renal Disease (MDRD) formula. The secondary endpoints include assessment of the following at 12, 24 and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection. Results We expect that addition of TCZ to SOC will slow down the decline of graft function in kidney transplant recipients with caAMR. Conclusion Currently there is no effective treatment for caAMR. Based on the hypothesis that inhibition of IL-6 by TCZ will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR. If TCZ is found to be effective, our study has the potential to improve long-term graft survival and quality of life, reduce morbidity and mortality in kidney transplant patients as well as lower the health care costs.

#1216 Comparable outcomes for old, older and very old deceased donors in old kidney transplant recipients

Abstract Background and Aims Old patients (≥ 65 years) make up almost 1/3 of the waiting list for kidney transplantation in the Netherlands, and this proportion continues to rise. These patients have a high waitlist mortality and benefit from early transplantation, even with kidneys from older or ‘marginal’ donors. Transplanting marginal donor kidneys may help to cut the proportion of elderly patients on the waiting list and improve clinical outcomes. More epidemiological support regarding the graft outcomes of old, older and very old donor kidneys is needed to support clinicians in accepting these kidneys. We therefore studied the outcomes of these kidneys in old recipients. Method Retrospective cohort study of all kidney transplant recipients ≥ 65 years with a deceased donor ≥ 65 years in the Netherlands between 2005 and 2022. Discarded kidneys from deceased donors ≥ 65 years in the same time period were included as well. Donors were categorized into old (65-69 years, OD), older (70-74, OD+) and very old (75+, OD++). Results We included 1301 transplantations from donors ≥ 65 years, of which 435 from an OD+ and 90 from an OD++. Median recipient age was 69 years (66 - 72), 67% was male. The transplanted OD+ and OD++ kidneys were more often from DBD donors (OD 42%, OD+ 51.3%, OD++ 70%, P < 0.01) with lower nadir creatinine compared to the OD kidneys (61.0 umol/l [51.0, 74.0] vs. OD+ 59.0 [49.0, 72.0] P = .034, vs OD++ 58.0 [49.0, 64.5] P = .021). Patient survival was similar for recipients of OD, OD+ and OD++ kidneys at one year (91% vs 89% vs 93%, respectively; Plog-rank = 0.3) and at five years (60% vs 60% vs 64%; Plog-rank = 0.2) after transplantation. Additionally, in multivariable Cox regression, donor age category was not associated with recipient mortality risk (Ref = OD. OD+: P = .7; OD++: P = .2). Death-censored graft survival was ≥92% in all groups after 1 year, and did not differ significantly between donor age categories (PGray's = 0.2). Results remained non-significant in multivariate Cox regression (Ref = OD, OD+: P = .942; OD++: p = 0.403). Kidneys offered but not accepted for transplantation (before procurement) had a higher serum nadir creatinine in comparison with transplanted kidneys (68 umol/L [56 - 84] vs 61 umol/L [51 - 78], P < .001), and were more often from DCD donors (79% vs 53%, P < .001). However, donor characteristics of many discarded kidneys resembled that of successfully transplanted kidneys. Conclusion Recipient and graft survival are good and similar for old patients receiving kidneys from old, older and very old deceased donors. These findings may contribute to a wider acceptance of kidneys from these donors.

#3077 Activity and chronicity index as graft lost predictors in kidney transplant with antibody mediated rejection or isolated microvascular inflammation

Abstract Background and Aims Antibody mediated rejection (ABMR) is the major cause of graft lost in kidney transplant (KT) recipients. Banff classification considers active ABMR (aABMR) and chronic active ABMR (caAMBR) but does not consider isolated microvascular inflammation (iMVI). Considering histologic lesions in kidney biopsies (KB), activity (AI) and chronicity index (CI) have been developed. Only CI ≥4 has been associated to worse graft survival in ABMR, yet the prognostic value of AI and CI in iMVI is still unknown. Our aim was to evaluate chronicity and activity index as prognostic tools in ABMR and iMVI. Method Retrospective study of KT recipients (1987-2022) with KB (2013-2022) with ABMR (category 3, Banff’2019) [group 1] and iMVI [group 2]. We evaluated AI ([glomerulitis (g) + peritubular capillaritis (ptc), arteritis (v) + C4dscore] e CI ([interstitial fibrosis (ci), tubular atrophy (ct), chronic vasculopathy (cv), and 2xchronic glomerulopathy (2cg) scores)]). Our aim was to evaluate chronicity and activity index as prognostic tools in ABMR and iMVI. Results One hundred thirty-nine KT with aABMR (n=48) and caABMR (n=46) (group 1) and MVIi (n=45) (group 2). Graft loss along time of follow-up (35 [15-69] months) was higher in group 1 (41.5% vs 22.2%; p=0.02). AI was higher in group 1 (4 [3-4.5] vs. 2 [2-4]; p<0.001) and CI similar in both groups (4 [3-7] vs. 4 [4-6]; p=0.7). In the multivariate analysis CI (per unit increase) with HR 1.24 [1.09-1.42; p=0.001] and IA ≥4 in ABMR with HR 2.23 [1.08-4.58; p=0.029]. Death-censored graft survival was worse in IA. IA≥ 4 e IC ≥4 La supervivencia del injerto muerte-censurada fue peor en el grupo RH con IA≥ 4 e IC ≥4 (Fig. 1). Conclusion Our findings suggest that the activity index in ABMR and the chronicity index both in ABMR and iMVI are valuable prognostic tools.

#2149 Kidney transplantation outcomes in lupus nephritis

Abstract Background and Aims Kidney transplantation (KT) is the renal replacement therapy of choice in patients with lupus nephritis (LN) who progress to end-stage renal disease (ESRD). The latest Spanish guidelines recommend the use of hydroxychloroquine after KT in these patients. Our study aims to analyze KT outcomes in patients with LN in our center. Method Retrospective cohort study, which included all KT with a diagnosis of LN who underwent KT between April 1982 and November 2023 at Puerta del Mar University Hospital (Spain). Each KT recipient with LN was matched with two controls from the same institution by age, sex and type of donor during the same period. We collected clinical and demographical characteristics, as well as immunosuppressive (IS) therapy after KT. We analyzed the death-censored graft survival and patient survival and compiled the causes of death and graft loss, comparing them with the control group. We documented LN recurrences, KT rejections, and incidence of CMV and BK infection. Results In this period, 2055 KTs were performed in our center, of which 39 had a diagnosis of LN (1.9%). Seventy eight controls were selected. The majority of KTs were women (89.7%) with a mean age of 44 years. Induction therapy was used in 85.2% of KT with Thymoglobulin (63%) or Basiliximab (27%). Maintenance IS therapy was based on tacrolimus (93.5%), cyclosporine (6.5%), mycophenolate (100%) and prednisone (100%). Only 4 patients (10.2%), the latest ones, received hydroxychloroquine after KT. Death-censored graft survival at 1 year (87.1% SLE vs. 88.5% Non-SLE), 5 years (74.9% SLE vs. 80.8% Non-SLE), and 10 years (65.6% SLE vs. 69.5% Non-SLE) and patient survival at 1 year (97.1% SLE vs. 100% Non-SLE), 5 years (93.7% SLE vs. 95.3% Non-SLE), and 10 years (93.7% SLE vs. 91.7% Non-SLE) were similar in both groups. No graft was lost because of recurrent LN. No significant differences were found neither in the causes of death nor between the causes of graft loss. The incidence of CMV and BK infection and KT rejection rates were similar in both groups. Conclusion KT is an excellent therapeutic alternative in LN with ESRD. Despite the low use of hydroxychloroquine in our series, no recurrence of LN was detected and the KT outcomes were similar to the control group.

#153 The risk of post-transplant recurrent immunoglobulin A nephropathy: the association with post-transplant steroid use

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common cause of kidney failure among glomerulopathies worldwide and it is reported that approximately 6-7% of all kidney transplantation is due to IgAN. It is well known that IgAN can recur in the kidney allograft and previous studies suggest that recurrent IgAN is the third most common cause of graft loss in patients with IgAN as primary disease. There is currently no effective treatment for recurrent IgAN, and the main goal is therefore to prevent recurrence in the allograft. Post-transplant steroid therapy is a cornerstone in many immunosuppressive regimens, but steroid treatment also come with several side effects leading to the use of steroid-free protocols. Controversy remains as to whether the use of steroid affects the risk of recurrent IgAN. Previous, retrospective studies report widely divergent associations between the use of steroids and the risk of recurrent IgAN and thus, more research on the association between steroid use and the risk of recurrent IgAN is warranted. We examined this by taking advantage of the fact that two different standard immunosuppression protocols have been employed at two Danish transplantation centers, of which one included steroids and the other did not. The patients treated at the two transplantations centers were otherwise similar with respect to ethnicity, socio-economic status and other aspects of treatment differing only by regional residency. This provided a unique opportunity to compare the association between steroid use, recurrence rate and graft survival. We furthermore aimed to identify potential risk factors for recurrent IgAN. Method A retrospective cohort study including all adult patients (age ≥ 18 years) with biopsy-proven IgAN and a first-time kidney-only transplantation from 1990 to 2020 at either Aarhus University Hospital or Odense University Hospital using a steroid containing or a steroid free post-transplant immunosuppressive protocol, respectively. Renal transplant patients with IgAN were identified from the Danish Nephrology Registry and data on medical treatment, graft survival and histopathological evidence of recurrent IgAN were extracted from electronic medical journals. Data is presented by Aalen-Johansen and Kaplan-Meier plot, and associations between risk factors for recurrent IgAN were analyzed by cox-regression. Results A total of 120 first-time kidney recipients were included in the study. Biopsy-proven, recurrent IgAN was identified in 17 (14.2%) recipients. The median time from transplantation to recurrence was 2.91 years (IQR 0.89−5.60). Only one of 18 (15%) recipients adhering to steroid-free protocol was diagnosed with recurrent IgAN during the study period. The accumulated use of steroid as part of the immunosuppression regime was not associated with the risk of recurrent IgAN (unadjusted HR (95% CI) =1.02 (0.94−1.12)). Transplantation with genetically related living donor was associated with a greater risk of recurrent IgAN compared with non-genetically related ((unadjusted HR (95% CI) = 3.90 (1.37−11.10)) and recipients with recurrent IgAN were more likely to be younger at time of been diagnosed with IgAN and had a shorter time from being diagnosed to kidney failure when compared to recipients with non-recurrent IgAN. There were no associations between the risk of recurrent IgAN and induction therapy or HLA-mismatches. The 10-year death censored graft survival was 45% for recipients with recurrent IgAN, compared to 80% for recipients with non-recurrent IgAN. Conclusion The risk of recurrent IgAN after kidney transplantation was not associated with the use of steroids as part of the immunosuppression protocol, whereas recipients receiving a kidney from a genetic related donor appeared to have a higher risk of recurrent IgAN.

Clinical and histopathological characteristics of acute kidney injury in a cohort of brain death donors with procurement biopsies.

Kidney biopsies are routinely used for diagnostic and prognostic purposes but their utility in the intensive care unit (ICU) setting is limited. We investigated the associations of clinical and histopathological risk factors with ICU-acute kidney injury (AKI) in donors with brain death (DBD) with kidneys of lower quality and procurement biopsies. Overall,221 donors with brain death, 239 biopsies and 197 recipients were included. The biopsies were reread and scored according to the Banff recommendations. Clinical and histopathological data were compared between donors with and without AKI defined by serum creatinine and by urine output. Logistic regression analysis was applied to identify independent clinical and histopathological risk factors for both phenotypes. Lastly, the impact of each AKI phenotype on outcome was explored.AKI was diagnosedbased on the RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease)AKIN (Acute Kidney Injury Network) orKDIGO (Kidney Disease Improving Global Outcomes) criteria. Acute kidney injury occurred in 65% of donorsbased both uponserum creatinine and by urine output. Serum creatinine was able to better discriminate AKI. Multiorgan failure and severe AKI were captured by serum creatinine, and hemodynamic instability by urine output. Donors with serum creatinine-AKI showed lower chronic macrovascular scores, while donors with urine output-AKI had higher chronic microvascular and tubulointerstitial scores. Tubular injury was similar between the subgroups. Except for delayed graft function and one-year death-censored graft survival, the other short-term recipient outcomes were similar for both AKI phenotypes. Serum creatinine is more suitable than urine output for defining AKI in donors with brain death. There are distinct clinical risk factors for each AKI-ICU phenotype. Donor AKI phenotype does not predict the recipient´s prognosis. Kidney biopsies do not seem to confer any tangible benefit in defining AKI indonors with brain death.

Live-donor kidney transplant outcome prediction (L-TOP) using artificial intelligence.

Outcome prediction for live-donor kidney transplantation improves clinical and patient decisions and donor selection. However, the concurrently used models are of limited discriminative or calibration power and there is a critical need to improve the selection process. We aimed to assess the value of various artificial intelligence (AI) algorithms to improve the risk stratification index. We evaluated pre-transplant variables among 66914 live-donor kidney transplants (performed between 01/12/2007-01/06/2021) from the United Network of Organ Sharing database, randomized into training (80%) and test (20%) sets. The primary outcome measure was death-censored graft survival. We tested four machine learning models for discrimination (time-dependent concordance index, CTD, and area under the ROC curve) and calibration (integrated Brier score, IBS). We used decision curve analysis to assess the potential clinical utility. Among the models, the deep Cox mixture model showed the best discriminative performance (AUC=0.70, 0.68, and 0.68 at 5, 10, and 13 years post-transplant, respectively). CTD reached 0.70, 0.67, and 0.66 at 5, 10, and 13 years post-transplant. The IBS score was 0.09, indicating good calibration. In comparison, applying the Living Kidney Donor Profile Index (LKDPI) on the same cohort produced a CTD of 0.56 and an AUC of 0.55-0.58 only. Decision curve analysis showed an additional net benefit compared to the LKDPI, 'Treat all' and 'Treat None' approaches. Our AI-based deep Cox mixture model, termed Live-Donor Kidney Transplant Outcome Prediction outperforms existing prediction models, including the LKDPI, with the potential to improve decisions for optimum live donor selection by ranking potential transplant pairs based on graft survival. This model could be adopted to improve the outcomes of paired exchange programs.

Incomplete reporting of clinically significant acute rejection episodes in the national kidney transplant registry

Administrative claims data could provide a unique opportunity to identify acute rejection (AR) events using specific antirejection medications and to validate rejected data reported to the Organ Procurement and Transplantation Network. This retrospective cohort study examined differences in registry-reported events and those identified using claims data among adult kidney transplant recipients from 2012 to 2017 using Standard Analysis Files from the US Renal Data System. Rejection rates, survival estimates, and center-level differences were assessed using each approach. Among 45 880 first-time kidney transplant recipients, we identified 3841 AR events within 12 months of transplant reported by centers in the registry; claims data yielded 2945 events. Of all events occurring within 12 months of transplant, 48.5% were reported using registry only, 32.9% were identified using claims only, and 18.6% were identified using both approaches. A 3-year death-censored graft survival probability was 90.0%, 88.4%, and 81.2% (P < .001) for ARs identified using registry only, claims data only, and both approaches, respectively. The large discordance between registry-reported and claims-based events suggests incomplete and potentially inaccurate reporting of events in the Organ Procurement Transplant Network registry. These findings have important implications for analyses that use AR data and underscore the need for improved capture of clinically meaningful events.

Comparing the prognostic performance of iBOX and biopsy-proven acute rejection for long-term kidney graft survival

Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/− abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR’s prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P < .01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.

A2/A2B to B kidney transplantation outcomes: A single center 7-year experience.

Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants. This retrospective, single-center analysis included all adults who received A2/A2B to B deceased donor kidney transplants from December 2014 to June 2021 compared to B to B recipients. The effects of pre-transplant IgM/IgG titers, stratified as ≤1:8 and ≥1:16, on death-censored, rejection-free, and overall graft survival were tested. Fifty-three A2/A2B and 114 B to B adults were included with a median follow-up time of 32 months. Overall graft survival, patient survival, and rejection-free graft survival did not differ between the two groups. There were no differences between the groups' overall kidney function values (p>.80) or their temporal trajectories (time by group interaction p>.11). Unadjusted death-censored graft survival was lower in A2/A2B to B compared to B recipients (p=.03), but the effect was not significant (p=.195) after adjusting for any readmissions (p=.96), rejection episodes (p<.001) or BK infection (p=.76). We did not detect an effect of pre-transplant titer group on death-censored (p=.59), rejection-free (p=.61), or overall graft survival (p=.26) CONCLUSIONS: A2/A2B to B kidney transplants have comparable overall patient and graft survival, rejection-free graft survival, and longitudinal renal function compared to B to B transplants at our center. Allograft survival outcomes were not significantly different between patients with low and high pre-transplant anti-A1 IgM/IgG titers.

Deceased-Donor Kidney Transplant Outcome Prediction Using Artificial Intelligence to Aid Decision-Making in Kidney Allocation.

In kidney transplantation, pairing recipients with the highest longevity with low-risk allografts to optimize graft-donor survival is a complex challenge. Current risk prediction models exhibit limited discriminative and calibration capabilities and have not been compared to modern decision-assisting tools. We aimed to develop a highly accurate risk-stratification index using artificial intelligence (AI) techniques. Using data from the UNOS database (156,749 deceased kidney transplants, 2007-2021), we randomly divided transplants into training (80%) and validation (20%) sets. The primary measure was death-censored graft survival. Four machine learning models were assessed for calibration (integrated Brier score [IBS]) and discrimination (time-dependent concordance [CTD] index), compared with existing models. We conducted decision curve analysis and external validation using UK Transplant data. The Deep Cox mixture model showed the best discriminative performance (area under the curve [AUC] = 0.66, 0.67, and 0.68 at 6, 9, and 12 years post-transplant), with CTD at 0.66. Calibration was adequate (IBS = 0.12), while the kidney donor profile index (KDPI) model had lower CTD (0.59) and AUC (0.60). AI-based D-TOP outperformed the KDPI in evaluating transplant pairs based on graft survival, potentially enhancing deceased donor selection. Advanced computing is poised to influence kidney allocation schemes.

Transplant Candidates of 70+ Years Have Superior Survival If Receiving Pre-Emptively a Living Donor Kidney.

Background: The number of kidney transplant recipients over 70 years of age is increasing but detailed data on patient and graft survival in the modern era of immune suppression are few. Methods: A single-center cohort of patients of 70 years and older (n = 349) at time of kidney transplantation from 2010-2020 were followed until January 2023. Results: The median age was 73 years with a median follow-up of 4.3 years. Fifty percent of recipients of a living donor kidney (LDK, n = 143) received their graft pre-emptively. Cumulative death-censored graft survival was excellent in the LDK group and reached 98% at 5 years vs. 85% in the deceased donor kidney (DDK) group. Primary non-function (38%) and rejection (43%) were the major causes of graft loss in the first year after DDK transplantation. Rejection-related graft loss was 4.6% during follow-up. Median recipient survival was superior in the subgroup of pre-emptively transplanted LDK patients compared to non-pre-emptively LDK transplanted patients (11.1 versus 6.2 years). Non-pre-emptively transplanted patients had a significantly increased incidence of infection (HR 3.81, 1.46-9.96) and cardiovascular-related causes of death (HR 3.35, 1.16-9.71). Pre-emptive transplantation was also associated with a significantly improved graft survival in the DDK recipients but this result was confounded by significantly better HLA matching and younger donor age in this group. Conclusions: Pre-emptive LDK transplantation in patients of 70 years or older confers superior graft and recipient survival.

Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study)

BackgroundChronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.DiscussionNo effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.Trial registrationClinicalTrials.gov NCT04561986. Registered on September 24, 2020

The Kidney Not Taken: Single-Kidney Use in Deceased Donors.

The nonuse rate for kidneys recovered from deceased donors is increasing, rising to 27% in 2023. In 10% of these cases, 1 kidney is transplanted but the mate kidney is not. We conducted a retrospective, single-center cohort study from December 2001 to May 2023 comparing single kidneys transplanted at our center (where the contralateral kidney was not used) to kidneys where both were transplanted separately, at least 1 of which was at our center. We performed 395 single deceased-donor kidney transplants in which the mate kidney was not transplanted. Primary reasons for mate kidney nonuse were as follows: no recipient located or list exhausted (33.4%), kidney trauma or injury or anatomic abnormalities (18.7%), biopsy findings (16.7%), and poor renal function (13.7%). Mean donor and recipient ages were 51.5 ± 14.2 and 60 ± 12.6 years, respectively. Mean kidney donor profile index was 73% ± 22%, and 104 donors (26.3%) had kidney donor profile index >85%. Mean cold ischemia was 25.6 ± 7.4 hours, and 280 kidneys (70.7%) were imported. Compared with 2,303 concurrent control transplants performed at our center, primary nonfunction or thrombosis (5.1% single vs 2.8% control) and delayed graft function (35.4% single vs 30.1% control) were greater with single-kidney use (both p < 0.05). Median patient and death-censored graft survival were shorter in the single group (11.6 vs 13.5 years, p = 0.03 and 11.6 vs 19 years, p = 0.003), although the former was at least double median survival on the waiting list. In patients with functioning grafts in the single-kidney group, 1-year mean serum creatinine was 1.77 ± 0.8 mg/dL and estimated glomerular filtration rate was 44.8 ± 20 mL/min/1.73 m 2 . These findings suggest that many mate kidneys are being inappropriately rejected, given the acceptable outcomes that can be achieved by transplanting the single kidney in appropriately selected recipients.

Sarcopenic obesity is associated with adverse outcomes after kidney transplantation: a retrospective cohort study.

Sarcopenia was found to be a poor prognostic factor in kidney transplant recipients, but the role of sarcopenia obesity remains unclear. This study aimed to explore the effect of sarcopenic obesity on kidney transplantation. A retrospective analysis was performed on kidney transplant recipients between 2015 and 2019. Pretransplant CT scans were utilized to assess sarcopenia and visceral obesity. Based on the presence or absence of sarcopenia and visceral obesity, the recipients were classified into four distinct groups. The recipients were categorized into four groups based on their characteristics: the nonsarcopenic nonobesity group (n = 493, 49.85%), the nonsarcopenic obesity group (n = 248, 25.08%), the sarcopenic nonobesity group (n = 188, 19.01%), and the sarcopenic obesity group (n = 60, 6.07%). Multivariate analysis, identified sarcopenic obesity was as an independent risk factor for mortality following kidney transplantation (adjusted hazard ratio, 5.861; 95% confidence interval [CI]: 1.627-21.108; P = 0.007). Additionally, sarcopenic obesity was associated with an increased risk of delayed graft function (adjusted odds ratio [aOR], 3.342; 95% CI 1.421-7.745; P = 0.005), perioperative incision infection (aOR, 9.654; 95% CI 1.572-60.648; P = 0.011), perioperative pulmonary infection (aOR, 2.557; 95% CI 1.208-5.215; P = 0.011), and readmission within 3months (aOR, 2.100; 95% CI 1.051-4.017; P = 0.029). While sarcopenic obesity was found to be associated with impaired graft renal function, it did not show a significant correlation with death-censored graft survival or quality of life. The presence of sarcopenic obesity prior to kidney transplantation represents an independent risk factor for mortality, and it is also linked to a range of unfavorable outcomes.

Protocol liver biopsy predicts graft survival after liver transplantation.

The use of protocol liver biopsy to monitor liver allograft status remains controversial. There is limited data from modern transplantation populations that includes protocol biopsies to evaluate its value in predicting clinical outcomes. All protocol liver biopsies were identified from 875 patients who underwent liver transplantation at Helsinki University Hospital between 2000 and 2019. Each histologic component was analyzed for its ability to predict long-term outcomes, especially graft survival. We determined the frequency of significant biopsy findings based on the Banff working group definition. Liver function tests (LFTs) and clinical markers were evaluated for their ability to predict significant biopsy findings. In total, 867 protocol liver biopsies were analyzed. Significant findings were identified in 20.1% of the biopsies. In the first protocol biopsy, steatohepatitis (hazard ratio [HR] 3.504, p=.03) and moderate or severe congestion (HR 3.338, p=.04) predicted graft loss. The presence of cholangitis (HR 2.563, p=.04), necrosis (HR 7.635, p<.001), mild congestion (HR 4.291, p=.009), and significant biopsy finding (HR 2.540, p=.02) predicted inferior death-censored graft survival. While the degree of elevation of LFTs was positively associated with significant biopsy findings, the discrimination was poor (AUC.572-.622). Combined LFTs and clinical risk factors remained suboptimal for discriminating significant biopsy findings (AUC.696). Our findings support the use of protocol liver biopsies after liver transplantation since they frequently revealed changes associated with long-term outcomes, even when LFTs were normal.

Outcomes of Kidneys Transplanted From Hepatitis C Viremic Donors to Naive Recipients From an Appalachian Rural Kidney Transplant Program.

Before the advent of direct-acting antiviral therapy for hepatitis C virus, a large proportion of kidneys from donors with hepatitis C viremia were discarded. Hepatitis C virus is now amenable to effective treatment with excellent seronegativity rates. In this study, we review the outcomes of hepatitis C viremic kidneys transplanted into hepatitis C-naive recipients. In this retrospective observational study, we examined 6 deceased donor kidneys with hepatitis C viremia that were transplanted into hepatitis C-naive recipients between March 2020 and April 2021 at a single center. Because of health insurance constraints, patients were treated for hepatitis C virus with glecaprevir/pibrentasvir for 8 weeks following seroconversion posttransplant. Primary outcome measured was viral seroconversion; secondary outcomes included graft function, posttransplant complications, and all-cause mortality. On average, patients seroconverted 6 days (range, 4-10 d) after transplant and began treatment 26 days (range, 15-37 d) after seroconversion. An 8-week course of antiviral treatment was successful in preventing acute hepatitis C virus infection in all patients. Posttransplant median creatinine was 1.96 mg/dL (range, 1-4.55 mg/dL), whereas median estimated glomerular filtration rate was 41.33 mL/min/1.73 m2 (range, 17-85 mL/min/1.73 m2). Patient survival rate was 66.7%, and death-censored graft survival rate was 100%. Two patients died from unrelated reasons: 1 from acute respiratory failure secondary to SARS-CoV-2 infection and 1 from posttransplant lymphoproliferative disorder. Two patients developed allograft rejection posttransplant (1 developed antibody mediated rejection, 1 developed borderline T-cell-mediated cellular rejection). Other major complications included neutropenia, fungal rash, SARS-CoV-2 infection, cytomegalovirus, BK virus, and Epstein-Barr virus reactivation. Use of hepatitis C-viremic donor kidneys for transplant is a safe option and has great potential to increase the kidney donor pool, as long as high index of suspicion is maintained for allograft rejection and opportunistic infections.