Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study

Donor‐specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001‐1.03, P = .047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04‐4.27, P = .039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow‐up is necessary to determine the impact of DSA on other important outcomes.     

Early findings of prospective anti‐HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience

The significance of donor‐specific antibodies (DSA) is not well known in the setting of pancreas transplantation. Since December 2009, we prospectively followed pancreas transplant patients with single‐antigen‐luminex‐bead testing at one, two, three, six, and then every six months for the first two yr. Thirty‐five of the 92 patients that underwent pancreas transplantation (13 pancreas‐alone [PTA], 20 with a kidney [SPK], and two after a kidney [PAK]) agreed to participate in study. Median age at transplant was 45 yr and follow‐up was 23 months. Majority were Caucasian (n = 33) and male (n = 18). Rabbit anti‐thymocyte globulin induction was used. Median HLA‐mismatch was 4.2 ± 1.1. Eight patients (7SPK, 1PAK) developed post‐transplant DSA at median follow‐up of 76 d (26–119), 1 SPK had pre‐formed DSA. Seven patients had both class I and class II DSA, one with class I and one with class II only. Mean peak class I DSA‐MFI was 3529 (±1456); class II DSA‐MFI was 5734 (±3204) whereas cumulative DSA MFI (CI + CII) was 9264 (±4233). No difference was observed in the patient and donor demographics among patients with and without DSA. One patient in non‐DSA group developed acute cellular rejection of pancreas. From our data it appears that post‐transplant DSA in pancreas allograft recipients may not impact the early‐pancreatic allograft outcomes. The utility of prospective DSA monitoring in pancreatic transplant patients needs further evaluation and long‐term follow‐up.     

Clinical impact of preformed donor‐specific denatured class I HLA antibodies after kidney transplantation

Class I single‐antigen flow beads (SAFB) carry native and denatured human leukocyte antigen (HLA) molecules. Using a cohort of 179 class I HLA‐sensitized kidney recipients, we described incidence and clinical relevance of preformed denatured HLA donor‐specific antibodies (DSA) using two different assays: an acid‐treated SAFB assay (anti‐dHLA DSA) and the iBeads assays (SAFB+/iBeads‐ DSA). Eighty‐five class I DSA were found in 67 patients (median mean fluorescence intensity [MFI] of 1729 [range 520–13 882]). Anti‐dHLA and SAFB+/iBeads‐ DSA represented 11% and 18% of class I DSA and were mainly low MFI DSA (500–1000 MFI). Concordance between these two assays was good (90%). None of the patients with only class I anti‐dHLA DSA or only SAFB+/iBeads‐ DSA developed acute clinical antibody‐mediated rejection in the first‐year post‐transplantation, and their five‐yr death‐censored graft survival was similar to that of patients without DSA. Moreover, all these patients displayed a negative current T‐cell flow cytometry cross‐match. Therefore, both anti‐dHLA DSA and SAFB+/iBeads‐ DSA appear irrelevant, which could explain the good outcome observed in some patients with preformed class I DSA.     

Donor‐specific anti‐HLA antibodies detected by Luminex: predictive for short‐term but not long‐term survival after heart transplantation

In heart transplantation, the clinical significance of pretransplant donor‐specific antibodies (DSA) detected by solid phase assay (SPA), which is more sensitive than the conventional complement‐dependent cytotoxicity (CDC) assays, is unclear. The aim was to evaluate SPA performed on pretransplant sera for survival after heart transplantation. Pretransplant sera of 272 heart transplant recipients were screened for anti‐HLA antibodies using CDC and SPA. For determination of pretransplant DSA, a single‐antigen bead assay was performed. The presence of anti‐HLA antibodies was correlated with survival. Secondary outcome parameters were acute cellular rejection, graft coronary vasculopathy and ejection fraction. In Kaplan–Meier analysis, SPA‐screening did not predict survival (P = 0.494), this in contrast to CDC screening (P = 0.002). However, the presence of pretransplant DSA against HLA class I was associated with decreased short‐term survival compared to non‐DSA (P = 0.038). ROC curve analysis showed a sensitivity of 76% and specificity of 73% at a cutoff of 2000 MFI. In contrast, the presence of anti‐HLA antibodies had no influence on long‐term survival, rejection incidence, and graft function. Thus, detection of DSA class I in pretransplant serum is a strong predictor of short‐term, but not long‐term survival and may help in the early management of heart transplant patients.     

VA‐ECMO for cardiogenic shock in the contemporary era of heart transplantation: Which patients should be urgently transplanted?

With the impending United Network for Organ Sharing (UNOS) heart allocation policy giving VA‐ECMO supported heart transplant (HT) candidates highest priority status (Tier 1), identifying patients in cardiogenic shock (CS) with severe and irreversible heart failure (HF) appropriate for urgent HT is critically important. In a center where wait times currently preclude this approach, we retrospectively reviewed 119 patients (ages 18‐72) with CS from 1/2014 to 12/2016 who required VA‐ECMO for >24 hours. Underlying aetiologies included postcardiotomy shock (45), acute coronary syndromes (33), and acute‐on‐chronic HF (16). Eighty‐four percent of patients (100) had ≥1 contraindication to HT with 61.3% (73) having preexisting contraindications (eg, multiorgan dysfunction and substance abuse), and 68.1% (81) experienced preclusive complications (eg, renal failure, coagulopathy, and infection). Potential HT candidates were significantly more likely to survive to discharge (potential HT candidates 84.2% vs preexisting contraindications 43.8% vs contraindications developing on VA‐ECMO 33.3%, P = 0.001). Among potential HT candidates, 11 (68.8%) were discharged without advanced therapies and 4 received durable left ventricular assist device (25.0%). Importantly, 1‐year survival was 100% for the 11 patients with follow‐up. Thus, further work is critical to define appropriate candidates for HT from VA‐ECMO while avoiding preemptive transplantation in those with otherwise favorable outcomes.     

Effect of recipient gender and donor‐specific antibodies on antibody‐mediated rejection after heart transplantation

Gender‐difference regarding antibody‐mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor‐specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single‐institution 6‐year cohort (2010‐2015), time to AMR was assessed, comparing men with women by survival analysis with a 1‐year death‐censored follow‐up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA‐, size‐ and sex‐mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1 year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard‐ratio [adj. HR] = 1.78 [1.06‐2.99]), P = .03) and the presence of pfDSA (adj. HR = 3.20 [1.80‐5.70], P < .001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR = 2.2 (P = .026) and MFI of pfDSA (per 1 MFI‐increase) adj. HR = 1.0002 (P < .0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender‐related difference in the severity of pfDSA.     

Discovery of non‐HLA antibodies associated with cardiac allograft rejection and development and validation of a non‐HLA antigen multiplex panel: From bench to bedside

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non‐HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody–negative, endothelial cell crossmatch–positive sera obtained from 12 cardiac allograft recipients at the time of biopsy‐proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non‐HLA antibodies associated with rejection (P < .1) including 4 newly identified non‐HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non‐HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non‐HLA antigens synergize with HLA donor‐specific antibodies and significantly increase the odds of rejection (P < .1). The non‐HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non‐HLA antibodies identifies cardiac transplant recipients at risk of rejection.     

Correlation of Luminex-Based Single Antigen Based Results With Complement-Dependent Cytotoxicity Crossmatch and Flow Cytometry Crossmatch Results: A Single-Center Experience From Istanbul

BackgroundThis study aimed to retrospectively investigate the correlation of mean Class I donor-specific antibody (DSA) intensity values detected in Luminex-based techniques with the results of complement-dependent cytotoxicity crossmatch (CDC-XM) and flow cytometry crossmatch (FC-XM) results.MethodsA total of 335 patients with kidney failure and their living donors whose CDC-XM, FC-XM, and single antigen based (SAB) tests were studied between 2018 and 2020 for transplant preparation from living donor candidates were included in the study. Patients were divided into 4 groups according to their mean fluorescence intensity (MFI) values of SAB assay.ResultsAnti-HLA antibodies (class I and/or class II) were detected using SAB in 91.6% patients included in the study (MFI >1000). Class I DSA was positive in 34.8% of patients with anti-HLA antibodies. When CDC-XM and FC-XM results were evaluated in the 4 groups separated according to MFI values, 3 patients with DSA MFI <1000 had negative CDC-XM and T-B-FC-XM results. Of 32 patients with DSA-MFI between 1000 and 3000, 93.75% (n = 30) had T-B-FC-XM or CDC-XM-negative results, and 6.25% (n = 2) had B-FC-XM-positive results. The CDC-XM, T, and B-FC-XM were negative in all 17 patients with DSA-MFI between 3000 and 5000. Our results showed that MFI >5834 DSA values were significantly correlated with positive T-FC-XM (P < .001), and MFI >6016 values were significantly correlated with positive CDC-XM (P = .002). In addition, MFI values >5000 were associated with both CDC-XM and FC-XM in our study.ConclusionsThe MFI values >5000 correlated with both CDC-XM and FC-XM.     

A case of successful desensitization using therapeutic plasma exchange in high-risk HLA incompatible kidney transplantation

Advances in immune suppression therapies and desensitization have made possible kidney transplantation regardless of HLA incompatibility. Single antigen bead assay (SAB) is a semi-quantitative estimation of the amount of human leukocyte antigen (HLA) antibodies present in the recipient plasma, and mean fluorescence intensity (MFI) generated gives this rough estimation of the antibodies present in the recipient. Here we present a case of successful kidney transplantation in a patient who expressed DSA with high MFI. A 33-yr-old male, diagnosed with chronic kidney disease (CKD) on regular maintenance hemodialysis, opted for second kidney transplant with his sibling as prospective donor and was referred to the department of Transplant Immunology for histocompatibility testing. Patient had HLA incompatibility with multiple DSA identified by SAB. Patient undergone 20 sessions of plasma exchange till discharge and finally till 6 months graft was functioning well. The authors thus conclude that the option of a high-risk HLA incompatible kidney transplant can be offered to recipients with high MFI DSA, who wish to undergo transplantation for end stage renal disease.     

Alemtuzumab dose adjusted for body weight is associated with earlier lymphocyte repletion and less infective episodes in the first year post renal transplantation – a retrospective study

The optimal dose of alemtuzumab for renal transplant induction is not known, and the doses reported in the literature vary. This study compares two separate dosing regimens of alemtuzumab in renal transplantation. The first is a standard fixed dose of 30 mg (SD), and the second is a dose adjusted for body weight at 0.4 mg/kg (AD). In this first year post‐transplant, there was no difference in patient [HR 0.64 (0.22–1.86), P = 0.39] or allograft survival [HR 1.18 (0.48–2.90), P = 0.72] between the two groups. There was also no difference in overall rejection‐free survival [HR 1.12 (0.79–1.58), P = 0.53]. However, absolute lymphocyte count was significantly higher at all measured time points in the first year in the AD group. There were also less episodes of urosepsis [HR 1.38 (1.03–1.85), P = 0.037] and fungal infection [HR 5.15 (2.00–13.28), P = 0.015] in the AD group compared with the SD group. This study shows that AD alemtuzumab is associated with earlier lymphocyte repletion and less infective episodes in the first year postrenal transplant, without increasing the risk of rejection. This work highlights the need for studies into the optimal dosing of monoclonal antibodies used in transplantation.     

Clinical impact of the baseline donor‐specific anti‐human leukocyte antigen antibody measured by Luminex single antigen assay in living donor kidney transplant recipients after desensitization therapy

The aim of this study is to investigate the clinical impact of donor‐specific anti‐HLA‐antibody (HLA‐DSA) baseline levels, measured using the Luminex single antigen assay (LSA), in living donor kidney transplantation (LDKT). Total 129 cases of LDKT were divided into four groups according to baseline mean fluorescence intensity (MFI) HLA‐DSA values: Strong (n = 6), >10 000; Moderate (n = 8), 5 000–10 000; Weak (n = 11), 1 000–5 000, Negative (n = 104), <1 000. Pretransplant desensitization (DSZ) was performed to decrease the MFI to weak or negative values before KT. Clinical outcomes in the four groups were compared. After DSZ, HLA‐DSA decreased to weak or negative levels in all patients; Acute rejections developed more frequently in strong group [5/6 (83.3%)] compared with other three groups (P < 0.05), and especially acute antibody‐mediated rejection (AAMR) developed almost exclusively in strong group [4/6 (66.7%)]. Strong HLA‐DSA levels at baseline were more predictive of AAMR than either type of XM (complement‐dependent lymphocytotoxicity or flow cytometry) in ROC analysis. Allograft function in this group showed significant deterioration during follow‐up compared with the other groups. In conclusion, strong HLA‐DSA levels at baseline are associated with worse allograft outcome even after successful desensitization; therefore, strict monitoring and strong maintenance immunosuppression may be required in such patients.     

De novo donor‐specific antibodies in belatacept‐treated vs cyclosporine‐treated kidney‐transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT‐EXT studies

Donor‐specific antibodies (DSAs) are associated with an increased risk of antibody‐mediated rejection and graft failure. In BENEFIT and BENEFIT‐EXT, kidney‐transplant recipients were randomized to receive belatacept more intense (MI)–based, belatacept less intense (LI)–based, or cyclosporine‐based immunosuppression for up to 7 years (84 months). The presence/absence of HLA‐specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid‐phase flow‐cytometry screening. Samples from anti‐HLA‐positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan‐Meier analysis, de novo DSA incidence was significantly lower in belatacept‐treated vs cyclosporine‐treated patients over 7 years in both studies (P < .01). In patients who developed de novo DSAs, belatacept‐based immunosuppression was associated with numerically lower MFI vs cyclosporine‐based immunosuppression. Although derived post hoc, these data suggest that belatacept‐based immunosuppression suppresses de novo DSA development more effectively than cyclosporine‐based immunosuppression.     

Is pre‐transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti‐HLA Luminex era? A retrospective study

We aimed to assess the correlation of anti‐angiotensin II type 1 receptor antibodies (anti‐AT1R‐Abs) before transplantation on a multicentric cohort of kidney transplant recipients (2008–2012), under tacrolimus and mycophenolate mofetil (MMF), screened by Luminex technology for anti‐HLA immunization. Anti‐AT1R antibody levels were measured by ELISA in pretransplantation sera of 940 kidney recipients from three French centers of the DIVAT cohort. Multivariable Cox models estimated the association between pretransplant anti‐angiotensin II type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R‐Abs higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative probability of clinically relevant (cr)‐ARE was 22.5% at 1 year post‐transplantation [95% CI (19.9–25.4%)]. The cumulative probability of graft failure and patient death were 10.6% [95% CI (8.4–13.3%)] and 5.7% [95% CI (4.0–8.1%)] at 3 years post‐transplantation, respectively. Multivariate Cox models indicated that pretransplant anti‐AT1R antibody levels higher than 10 U/ml were not significantly independently associated with higher risks of acute rejection episodes [HR = 1.04, 95% CI (0.80–1.35)] nor with risk of graft failure [HR = 0.86, 95% CI (0.56–1.33)]. Our study did not confirm an association between pretransplant anti‐AT1R antibody levels and kidney transplant outcomes.     

Influenza vaccination and humoral alloimmunity in solid organ transplant recipients

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti‐HLA antibodies were measured before and 4–8 weeks after influenza vaccination using a solid‐phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti‐HLA antibodies after vaccination, including one patient who developed donor‐specific antibodies (DSA) 8 months after vaccination. In patients with pre‐existing anti‐HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti‐HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti‐HLA antibodies. The incidence of development of anti‐HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.     

A Risk‐Prediction Model for In‐Hospital Mortality After Heart Transplantation in US Children

We sought to develop and validate a quantitative risk‐prediction model for predicting the risk of posttransplant in‐hospital mortality in pediatric heart transplantation (HT). Children <18 years of age who underwent primary HT in the United States during 1999–2008 (n = 2707) were identified using Organ Procurement and Transplant Network data. A risk‐prediction model was developed using two‐thirds of the cohort (random sample), internally validated in the remaining one‐third, and independently validated in a cohort of 338 children transplanted during 2009–2010. The best predictive model had four categorical variables: hemodynamic support (ECMO, ventilator support, VAD support vs. medical therapy), cardiac diagnosis (repaired congenital heart disease [CHD], unrepaired CHD vs. cardiomyopathy), renal dysfunction (severe, mild‐moderate vs. normal) and total bilirubin (≥ 2.0, 0.6 to <2.0 vs. <0.6 mg/dL). The C‐statistic (0.78) and the Hosmer–Lemeshow goodness‐of‐fit (p = 0.89) in the model‐development cohort were replicated in the internal validation and independent validation cohorts (C‐statistic 0.75, 0.81 and the Hosmer–Lemeshow goodness‐of‐fit p = 0.49, 0.53, respectively) suggesting acceptable prediction for posttransplant in‐hospital mortality. We conclude that this risk‐prediction model using four factors at the time of transplant has good prediction characteristics for posttransplant in‐hospital mortality in children and may be useful to guide decision‐making around patient listing for transplant and timing of mechanical support.     

The correlation of results of panel reactive antibody,identification, and single antigen beads in detection of anti-HLA antibodies: Istanbul Faculty of Medicine,tissue typing laboratory experience

BackgroundWe have performed a retrospective analysis of anti-HLA class I MHC and class II MHC antibodies measured using a single antigen bead (SAB) assay and a panel reactive antibody (PRA) assay.Material and methodsA group of 256 patients with end-stage renal disease (ESRD) was tested for anti-HLA antibodies in the tissue typing laboratory between 2017 and 2020. In the cohort, the serum samples of patients waiting for transplantation were tested. Both the PRA and SAB tests of these patients were analyzed using the Luminex (Immucor) method. The threshold of positivity was accepted as median fluorescence intensities (MFI) ≥1000 for PRA screening and MFI ≥750 for SAB screening.ResultsOverall, antibodies to HLA antigens were detected in 202 (78.9%) out of 256 patients in the PRA study. Antibodies against both class I/II antigens were detected only in 15.6% of these patients, whereas antibodies against only against class I HLA in 31.3% and only against class II HLA in 32.0%. By comparison, the SAB study found that 66.8% of patients were positive for HLA antigens. Furthermore, donor-specific antibodies (DSA) were detected in 52.0% of PRA-positive patients and 52.6% of SAB-positive patients. It was shown that 168 patients (83.2%) out of 202 PRA-positive patients were found to be SAB-positive. In addition, 51 patients negative in the SAB assay (94.4%) were also negative in the PRA assay. Statistical analysis established a significant correlation between the PRA and SAB positivity (p > 0.001).It was also shown that MFI ≥3000 PRA positivity for class I HLA antigens (p = 0.049) and MFI ≥5000 PRA positivity for class II antigens (p < 0.001) correlated with the SAB positivity in patients.ConclusionOur results showed the importance of both PRA and SAB assays to define the status of sensitization in patients.     

Pre‐existing donor‐specific antibodies are detrimental to kidney allograft only when persistent after transplantation

Donor‐specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty‐seven patients (15.5%) had pre‐existing DSA detected the day of transplantation. After 5 years, the pre‐existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years (P = 0.009), a history of previous transplantation (P = 0.039), the presence of class II DSA (P = 0.009), an MFI of preformed DSA >3500 (P < 0.001), and the presence of two or more DSA (P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody‐mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation.     

Eculizumab Salvage Therapy for Antibody‐Mediated Rejection in a Desensitization‐Resistant Intestinal Re‐Transplant Patient

The presence of elevated calculated panel reactive antibody (cPRA) and anti‐HLA donor specific antibodies (DSA) are high risk factors for acute antibody‐mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization‐resistant intestinal re‐transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18 000 MFI (mean fluorescent intensity) to below the positive cut‐off value of 3000 MFI and remains rejection free with a 2‐year follow‐up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization‐resistant patients.     

Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post–Heart Transplant Tumor Registry) comparing the epidemiological data, immu‐nosuppressive treatments and incidence of post‐HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post‐HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2–2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3–4.0, p < 0.004). OS during the 10‐year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post‐HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post‐HT tumors and should be taken into account when considering a patient for HT.     

Chronic kidney disease after heart transplantation: a single‐centre retrospective study at Skåne University Hospital in Lund 1988–2010

We aimed to study the incidence, predictors and outcome of chronic kidney disease (CKD) after heart transplantation (HT). All our HT patients 1988–2010 were considered for inclusion. Of these, 134 came for annual follow‐ups including evaluation of glomerular filtration rate (GFR) using iohexol clearance measurements, and the CKD‐EPI (adults) or Schwartz (children) formulae. Median GFR (Q1–Q3) (ml/min/1.73 m²) declined from 67.0 (50.0–82.0) during transplant assessment (TA) to 56.0 (45.0–69.0) at year 1, 53.0 (41.0–68.0) at year 5 and 44.5 (25.0–57.3) at year 10. The cumulative incidence of CKD ≥ stage 4 was 25% at 5 years and 41% at 10 years after transplantation. Proteinuria the first year post‐HT was the only predictor related (P < 0.05) to a higher rate of GFR decline (HR 5.15, 95% CI 1.23–21.55). GFR ≥60 as compared to <60 before HT, or a first‐year GFR decline <30% as compared to >30%, was moreover associated (P < 0.05) with a lower risk of death (HR 0.30, 95% CI 0.12–0.76 and HR 0.35, 95% CI 0.13–0.90, respectively). Notably, the CKD‐EPI and Schwartz formulae overestimated GFR by 28 ± 29% and 26 ± 33%, respectively. In conclusion, CKD in HT patients is common and associated with worse outcome. To avoid diagnostic delay, GFR estimating equations' validity in HT patients needs further study.