T-cell epitopes shared between immunizing HLA and donor HLA associate with graft failure after kidney transplantation

CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.Nephrolog

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Whole brain quantitative CBF, CBV, and MTT measurements using MRI bolus tracking: implementation and application to data acquired from hyperacute stroke patients.

A robust whole brain magnetic resonance (MR) bolus tracking technique based on indicator dilution theory, which could quantitatively calculate cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) on a regional basis, was developed and tested. T2*-weighted gradient-echo echoplanar imaging (EPI) volumes were acquired on 40 hyperacute stroke patients after gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) bolus injection. The thalamus, white matter (WM), infarcted area, penumbra, and mirror infarcted and penumbra regions were analyzed. The calculation of the arterial input function (AIF) needed for absolute quantification of CBF, CBV, and MTT was shown to be user independent. The CBF values (ml/min/100 g units) and CBV values (% units, in parentheses) for the thalamus, WM, infarct, mirror infarct, penumbra, and mirror penumbra (averaged over all patients) were 69.8 +/- 22.2 (9.0 +/- 3.0 SD); 28.1 +/- 6.9 (3.9 +/- 1.2); 34.4 +/- 22.4 (7.1 +/- 2.7); 60.3 +/- 20.7 (8.2 +/- 2.3); 50.2 +/- 17.5 (10.4 +/- 2.4); and 64.2 +/- 17.0 (9.5 +/- 2.3), respectively, and the corresponding MTT values (in seconds) were 8.0 +/- 2.1; 8.6 +/- 3.0; 16.1 +/- 8.9; 8.6 +/- 2.9; 13.3 +/- 3.5; and 9.4 +/- 3.2. The infarct and penumbra CBV values were not significantly different from their corresponding mirror values, whereas the CBF and MTT values were (P < 0.01). Quantitative measurements of CBF, CBV, and MTT were calculated on a regional basis on data acquired from hyperacute stroke patients, and the CBF and MTT values showed greater sensitivity to areas with perfusion defects than the CBV values. J. Magn. Reson. Imaging 2000;12:400-410

Automated Quantitative evaluation of diseased and nondiseased renal transplants With MR renography

To present a method of automated parametric quantification of dynamic MR enhancement curves of renal transplants and evaluate the disease-discriminating properties of the resulting MR renography (MRR) data

Improving outcomes for donation after circulatory death kidney transplantation:Science of the times

The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the current timeframe. To assess the impact of time on outcomes, we performed a time-dependent comparative analysis of outcomes of DCD and donation after brain death (DBD) kidney transplantations. Data of all 11,415 deceased-donor kidney transplantations performed in The Netherlands between 1990-2018 were collected. Based on the incidences of early graft loss, two eras were defined (1998-2008 [n = 3,499] and 2008-2018 [n = 3,781]), and potential time-related effects on outcomes evaluated. Multivariate analyses were applied to examine associations between donor type and outcomes. Interaction tests were used to explore presence of effect modification. Results show clear time-related effects on posttransplant outcomes. The 1998-2008 interval showed compromised outcomes for DCD procedures (higher incidences of DGF and early graft loss, impaired 1-year renal function, and inferior graft survival), whereas DBD and DCD outcome equivalence was observed for the 2008-2018 interval. This occurred despite persistently high incidences of DGF in DCD grafts, and more adverse recipient and donor risk profiles (recipients were 6 years older and the KDRI increased from 1.23 to 1.39 and from 1.35 to 1.49 for DBD and DCD donors). In contrast, the median cold ischaemic period decreased from 20 to 15 hours. This national study shows major improvements in outcomes of transplanted DCD kidneys over time. The time-dependent shift underpins that kidney transplantation has come of age and DCD results are nowadays comparable to DBD transplants. It also calls for careful interpretation of conclusions based on historical cohorts, and emphasises that retrospective studies should correct for time-related effects.Transplant surger