ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis.

Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49-0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90-1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72-4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl].

Long-term, prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients.

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m2 at 6 months and 52.5 ± 23.0 ml/min/1.73 m2 at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.

A limited sampling strategy to estimate exposure of once-daily modified release tacrolimus in renal transplant recipients using linear regression analysis and comparison with Bayesian population pharmacokinetics in different cohorts.

PURPOSE: Tacrolimus has a narrow therapeutic window. Measuring trough level (C0) as surrogate for drug exposure (AUC) in renal transplant recipients has limitations. Therefore, limited sampling strategies (LSS's) have been developed. For the newer modified release, once-daily formulation (Tac QD) LSS's are based on either linear regression analysis (LRA) or population pharmacokinetics with maximum a posteriori Bayesian (MAPB) estimation. The predictive performances of both methods were compared, also to LSS's as described in literature. METHODS: LSS's (maximally three sampling time points) were developed for Tac QD from full 24-h sampling by LRA in 27 Caucasian, stable renal transplant recipients. Performance for accuracy (mean absolute prediction error < 10%) and precision (root mean squared error < 15%) was quantified also after MAPB estimation in two independent groups (early and late post-transplant, n = 12 each). RESULTS: LRA determined a single 8 hours post-dose measurement (C8) to fulfil predefined criteria for accuracy (MAPE 3.41%) and precision (RMSE 4.28%). The best LSS contained C2, C8 and C12 for the stable (MAPE 2.42%, RMSE 3.1%) and the early post-transplant group (MAPE 2.46%, RMSE 3.14%). LRA did not include C0 for any LSS, unless it was forced into the model. MAPB estimation showed similar performance. CONCLUSIONS: In renal transplant patients, sampling in the elimination phase (C8) accurately predicted Tac QD exposure, contrary to C0. The 3-point sampling C2, C8 and C12 had the best performance and is also valid early post-transplant. These LSS's were similarly predictive with MAPB estimation. Dried blood spot could facilitate late sampling in clinical practice.

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients.

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival.

BACKGROUND: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. METHODS: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. RESULTS: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). CONCLUSION: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients.

BACKGROUND: Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. METHODS: We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. RESULTS: Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001). CONCLUSION: These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.

Living-donor transplantation leads to a major improvement in physical functioning: an observational study on the impact on potential donors and their recipients.

BACKGROUND: Prospective studies combining physical functioning (PF), physical activity (PA), and body composition (BC) after living donor transplantation/donation are scarce. We aimed to study differences in these parameters between kidney transplant recipients and their living donors by examining changes in these parameters in the first post-operative year in both groups. METHODS: Twenty-two kidney transplant recipients and 22 healthy kidney donors were included in this prospective longitudinal study with a follow-up until twelve months. PF was assessed by handgrip strength (HGS), and by the physical domains of health-related quality of life (HRQOL) using the Short Form-36 questionnaire [PF (SF-36 PF) and physical component summary (PCS) score]. BC was measured by the Body Composition Monitor©, and PA was measured by the SenseWear™ pro3. RESULTS: At baseline, recipients had significantly lower HGS (after adjustment for sex and body weight), SF-36 PF, PCS, and PA, as compared with their donors. In recipients HGS significantly increased in the first year after transplantation, but PA did not change in the first six months after transplantation. Furthermore, no significant increase in lean tissue mass was observed. For healthy donors no significant changes in these parameters were observed, with exception of SF-36 PF, which declined in the first three months after donation, but equaled baseline values after twelve months. CONCLUSION: Recipients showed impressive improvements in PF and the physical domains of HRQOL in the first year after transplantation, reaching levels of healthy kidney donors already three to six months after transplantation. On the contrary, living kidney donation did not show any deterioration of the investigated parameters, supporting little impact for well-screened donors, while there is high benefit for transplant recipients.

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

The development of D antibodies after D-mismatched kidney transplantation in a setting of reduced immunosuppression.

BACKGROUND: D antigens are not taken into account in the allocation of solid organs. Female transplant recipients with D antibodies as a consequence of D-mismatched kidney transplantation may develop hemolytic disease of the fetus and newborn in future pregnancies. We examined D antibody development in transplant recipients who received D-mismatched kidney transplantation in absence of D prophylaxis and in a setting of reduced immunosuppression. STUDY DESIGN AND METHODS: From 1993 until 2015, a total of 1355 kidney patients received transplantations in our center of whom 156 received a D-mismatched graft. A retrospective analysis was conducted; frozen stored sera obtained from transplant recipients 3 months after transplantation were tested for irregular red blood cell (RBC) antibodies using a three-cell screening and an identification panel. In the case of D antibody positivity, additional testing was performed 1 month before transplantation. RESULTS: In seven of 156 (4.5%) transplant recipients we found irregular RBC antibodies after transplantation, of which five (3.2%) were determined to be D antibodies. We observed only one (0.6%) recipient without D antibodies before transplantation. CONCLUSION: Although the risk of D antibody development is considerably lower after D-mismatched kidney transplantation than D-mismatched pregnancy, anti-D prophylaxis may still be advisable for female transplant recipients of childbearing age.

Increase in tacrolimus exposure after steroid tapering is influenced by CYP3A5 and pregnane X receptor genetic polymorphisms in renal transplant recipients.

Background: Tacrolimus, a drug for prevention of rejection after kidney transplantation, has a narrow therapeutic window and is metabolized by the cytochrome P540 3A (CYP3A) system. Tacrolimus exposure increases after steroid tapering in many patients. The pregnane X receptor (PXR)-a mediator for CYP3A-has a steroid receptor and might regulate CYP3A5 activity depending on single nucleotide polymorphisms (SNPs) of CYP3A5 or PXR. This may contribute to differences in tacrolimus exposure after steroid tapering. Methods: In a cohort of renal transplant recipients, the influence of CYP3A5 and PXR SNPs (A7635G, C8055T and C25385T) on the dose-normalized Tacrolimus trough concentration (DnC0) and their potential interaction with each other after steroid taper were analysed by linear regression. Eligible were all 83 outpatient renal transplant patients on tacrolimus and steroids in a pharmacokinetic steady state at least 6 weeks after transplantation and whose blood was available for genetic analysis. Results: Compared with the CYP3A5*1/*3 genotype, the CYP3A5*3/*3 SNP showed a significantly stronger increase in DnC0 after steroid taper (+0.29 µg/L/mg; P = 0.002). Of the tested PXR SNPs, PXR G7635G individuals had a significantly stronger increase in DnC0 (compared with A7635A, +0.31 µg/L/mg; P = 0.02), with a weaker increase in A7635G heterozygotes (+0.17 µg/L/mg; P = 0.124). There was neither interaction nor association between CYP3A5 and PXR SNPs. Conclusions: The magnitude of the DnC0 increase due to steroid taper after renal transplantation is related to CYP3A5 SNPs. Independently, the PXR G7635G SNP is related to this increase, proving the role of PXR in tacrolimus metabolism.

Routine haemostasis testing before transplanted kidney biopsy: a cohort study.

Kidney biopsy can result in bleeding complications. Prebiopsy testing using bleeding time (BT) is controversial. New whole blood haemostasis tests, such as platelet function analyser-100 (PFA-100) and multiple electrode aggregometry (MEA), might perform better. We postulated that PFA-100 would be suitable to replace BT prebiopsy. In 154 patients, transplanted kidney biopsies were performed after measurement of bleeding time, PFA-100, MEA and mean platelet volume (MPV). Bleeding outcome (haemoglobin (Hb) drop, haematuria (±bladder catheterization), ultrasound finding of a bleeding, need for (non)surgical intervention and/or transfusion) after the biopsy was correlated to each test. Male-female ratio was 2:1. 50% had a surveillance biopsy at either three or 12 months. Around 17% (had) used acetylsalicylic acid (ASA) prebiopsy. Of 17 bleeding events, one subject needed a transfusion. Most bleeding events were Hb reductions over 1 mmol/l and all resolved uneventful. BT, PFA-100, MEA and MPV did not predict a bleeding outcome; prior ASA use however could (odds ratio 3.19; 95%-CI 1.06 to 9.61). Diagnostic performance data and Bland-Altman analysis showed that BT could not be substituted by PFA-100. ASA use was the best determinant of bleeding after kidney biopsy. Routine haemostasis testing prebiopsy has no added value.

Increased risk of graft failure and mortality in Dutch recipients receiving an expanded criteria donor kidney transplant.

Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07-1.63)] than in recipients 40-59 years [1.71 (1.44-2.02) P = 0.12 for comparison with ≥60 years] and recipients 18-39 years [1.92 (1.42-2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals.

ADHERE: randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus.

ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2 ; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2).

Effect of Breakfast on the Exposure of the Once-Daily Tacrolimus Formulation in Stable Kidney Transplant Recipients.

BACKGROUND: The once-daily Tacrolimus formulation (Tac ONCE-DAILY) has to be taken on an empty stomach. This is inconvenient for patients and may hamper compliance. The influence of food intake on the exposure of Tac ONCE-DAILY is unknown in transplant recipients. We compared the pharmacokinetics (PKs) of Tac ONCE-DAILY in stable kidney transplant recipients under fasted and fed conditions. METHODS: In an open-label, single-center, cross-over PK study, 27 stable kidney white transplant recipients (17 male, 10 female) treated with Tac ONCE-DAILY under fasted conditions were enrolled. Two 10-point 24-hour blood concentration time profiles [area under the blood concentration time curve from time 0 to 24 hours (AUC0-24)] were collected under steady state conditions. The primary objective was to investigate the effect of food on the PKs and relative bioavailability of Tac ONCE-DAILY. RESULTS: Twenty-seven stable renal transplant patients provided 1 AUC0-24 under fasted and fed conditions, respectively. AUC0-24, C24, and Cmax, were lower in the fed state and Tmax was 1 hour postponed. The 90% confidence interval ratio (fed: fasted) for AUC0-24 was 0.81-0.91 and for C24 0.82-0.92 (both P < 0.001). The majority (60%) had no significant change, but the change in AUC0-24 ranged from -38% to +29%. One trough level was below the target range after fed intake. CONCLUSIONS: When Tac ONCE-DAILY is ingested with standard continental breakfast, AUC0-24 and C24 decrease overall, with C24 in the therapeutic range in almost all patients. The convenient fed intake could promote therapy adherence. Given the possible significant change in exposure, we advise monitoring of the tacrolimus trough level 1 week after fed ingestion of Tac ONCE-DAILY.

Ellipro scores of donor epitope specific HLA antibodies are not associated with kidney graft survival.

In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants.

Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation.

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan-Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1-5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84-3.25) in deceased donation, and 2.22 (1.25-3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.

Improvements in kidney transplantation from donors after cardiac death.

To reduce the growing waiting list for kidney transplantation, we explored the limits of kidney transplantation from donors after cardiac death by liberally accepting marginal donor kidneys for transplantation. As the percentage of primary non-function (PNF) increased, we evaluated our transplantation program and implemented changes to reduce the high percentage of PNF in 2005, followed by a second evaluation over the period 2006-2009. Recipients of a kidney from a donor after cardiac death between 1998 and 2005 were analyzed, with PNF as outcome measure. During the period 2002-2005, the percentage of PNF increased and crossed the upper control limits of 12% which was considered as unacceptably high. After implementation of changes, this percentage was reduced to 5%, without changing the number of kidney transplantations from donors after cardiac death. Continuous monitoring of the quality of care is essential as the boundaries of organ donation and transplantation are sought. Meticulous donor, preservation, and recipient management make extension of the donor potential possible, with good results for the individual recipient. Liberal use of kidneys from donors after cardiac death may contribute to a reduction in the waiting list for kidney transplantation and dialysis associated mortality.

Kidneys from uncontrolled donors after cardiac death: which kidneys do worse?

Kidneys from uncontrolled donors after cardiac death (DCD) expand the donor pool, but are associated with more primary nonfunction (PNF) and delayed graft function (DGF) compared with more conventional donor kidneys. It remains unclear, which factors influence outcome of uncontrolled donation. Therefore, we studied which donor, graft, and recipient characteristics are associated with PNF in a large cohort study. The association between different characteristics and short-term graft function was analyzed for kidneys procured in the Maastricht region from 1 January 1981 to 1 July 2009. Patients were followed until 7 January 2010. A total of 135 uncontrolled donor kidneys were included in this study. The incidence of PNF and DGF was 22% and 61%, respectively. Increasing donor age is an independent risk factor for graft failure in a univariate analysis (OR 1.035, 95% CI 1.004-1.068, P = 0.028). Donor age remains strongly associated with PNF in a multivariate analysis (OR 1.064, 95% CI 1.013-1.118, P = 0.014). However, the predictive value of donor age alone is poor (AURC 0.640, 95% CI 0.553-0.721). Increasing donor age of uncontrolled DCD donors is a major risk factor for PNF. Other clinically relevant variables were not associated with PNF. Donor age is strongly associated with PNF and remains an important parameter in donor selection.

Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers.

Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions. Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient. Per case, nephrologists were asked to estimate the risk of adverse outcome and whether they would accept the offer for this patient, or for a patient of their own choice, and how certain they felt. These questions were repeated after revealing the risk of adverse outcome, calculated by a validated prediction model. Results: Sixty Dutch nephrologists completed the survey. The intraclass correlation coefficient of their estimated risk of adverse outcome was poor (0.20, 95% confidence interval [CI] 0.08-0.62). Interobserver agreement of the decision on whether or not to accept the kidney offer was also poor (Fleiss kappa 0.13, 95% CI 0.129-0.130). The acceptance rate before and after providing the outcome of the prediction model was significantly influenced in 2 of 6 cases. Acceptance rates varied considerably among transplant centers. Conclusion: In this study, the estimated risk of adverse outcome and subsequent decision to accept a suboptimal donor kidney varied greatly among transplant nephrologists. The use of a prediction model could influence this decision and may enhance nephrologists' certainty about their decision.