Donor and recipient age matching in heart transplantation: analysis of the UNOS Registry

The association of donor and recipient age with survival following adult heart transplantation has not been well characterized. The purpose of this study was to examine the impact of the relationship between donor and recipient age on post‐transplant survival. We retrospectively reviewed the 2005–2018 UNOS heart transplant database for all adult recipients undergoing first‐time isolated heart transplantation. The impact of donor and recipient age on survival was analyzed with Cox proportional hazards modeling using restricted cubic splines. A total of 25 480 heart transplant donor and recipient pairs met inclusion criteria. Unadjusted and adjusted Cox proportional hazards modeling demonstrated a near‐linear association between increasing donor age and decreased survival; in addition, older and younger recipient age was associated with decreased survival. After adjustment, there was no significant interaction between donor and recipient age. Older donors decreased survival similarly in both older and younger recipients. Increasing donor age and both younger and older recipient age are independently associated with worsened post‐heart transplant survival. The relationship between donor and recipient age does not significantly affect survival following heart transplant.     

Predictors and outcomes of delayed graft function after living‐donor kidney transplantation

Delayed graft function (DGF) following deceased donor kidney transplantation is associated with inferior outcomes. Delayed graft function following living‐donor kidney transplantation is less common, but its impact on graft survival unknown. We therefore sought to determine risk factors for DGF following living‐donor kidney transplantation and DGF's effect on living‐donor kidney graft survival. We analyzed living‐donor kidney transplants performed between 2000 and 2014 in the UNOS dataset. A total of 64 024 living‐donor kidney transplant recipients were identified, 3.6% developed DGF. Cold ischemic time, human leukocyte antigen mismatch, donor age, panel reactive antibody, recipient diabetes, donor and recipient body mass index, recipient race and gender, right nephrectomy, open nephrectomy, dialysis status, ABO incompatibility, and previous transplants were independent predictors of DGF in living‐donor kidney transplants. Five‐year graft survival among living‐donor kidney transplant recipients with DGF was significantly lower compared with graft survival in those without DGF (65% and 85%, respectively, P < 0.001). DGF more than doubled the risk of subsequent graft failure (hazard ratio = 2.3, 95% confidence interval: 2.1–2.6; P < 0.001). DGF after living‐donor kidney transplantation is associated with inferior allograft outcomes. Minimizing modifiable risk factors may improve outcomes in living‐donor kidney transplantation.     

Negative pretransplant serostatus for Toxoplasma gondii is associated with impaired survival after heart transplantation

Chronic Toxoplasma gondii infection is known to trigger potentially adverse immunoregulatory changes, but limited data exist on long‐term implications for heart transplant (HTX) recipients. We evaluated the risk of all cause mortality regarding T. gondii serostatus prior to HTX. Pre‐HTX T. gondii serostatus was obtained in 344 recipients and 294 donors. Mean age was 52.1 ± 10.2 years and mean follow‐up time after HTX was 5.7 (±5.5, median 3.5) years. All seronegative patients received prophylaxis with pyrimethamine/sulfomethoxazole or cotrimoxazol for 6 months after transplantation. Multivariate survival analysis adjusted for diabetes mellitus, pre‐HTX renal function, recipient age, type of primary immunosuppression (i.e. HTX before 2001), cytomegalovirus (CMV) high‐risk status, ischemic time, and number of treated rejection episodes was performed. Overall, 190 recipients (55.2% of total) were seronegative and 154 (44.8% of total) were seropositive for T. gondii prior to HTX. One hundred and fifty‐two recipients died during follow‐up (44.2% of total). Negative recipient Toxoplasma serostatus was associated with a significantly higher risk of all‐cause mortality (P = 0.0213). Recipient T. gondii serostatus did not influence the number of cellular or humoral rejection episodes. Analyses of specific causes of death showed a trend toward a higher number of infection‐related deaths in the seronegative subgroup (P = 0.13). No statistically significant effects of T. gondii donor/recipient seropairing, or seroconversion were observed. Negative preoperative serostatus for T. gondii in HTX recipients appears to be an independent risk factor associated with increased all‐cause mortality. The cause of impaired survival in Toxoplasma seronegative recipients is currently unclear; possible explanations include an alteration of immune‐reactivity/‐regulation or adverse effects of prophylactic medication.     

Inferior graft survival of hepatitis B core positive grafts is not influenced by post‐transplant hepatitis B infection in liver recipients—A 35‐year single‐center experience

Nonoptimal liver grafts, and among them organs from anti‐HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long‐term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti‐HBc+ graft. The 10‐year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti‐HBc‐ grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti‐HCV+ recipients (P = 0.005), and anti‐HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti‐HBc+ grafts developed post‐transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long‐term survival (P = 0.008). Development of post‐transplant HBV infection did not affect adjusted 10‐year graft survival (100% vs. 100%; P = 1). Anti‐HBc+ liver grafts can be transplanted with reasonable but inferior long‐term patient and graft survival. The inferior graft survival is not, however, related with post‐transplant HBV infection as long as early diagnosis and treatment take place.     

De Novo Donor HLA‐Specific Antibodies after Heart Transplantation Are an Independent Predictor of Poor Patient Survival

Preformed donor HLA‐specific antibodies are a known indicator for poor patient survival after cardiac transplantation. The role of de novo donor‐specific antibodies (DSA) formed after cardiac transplantation is less clear. Here we have retrospectively analyzed 243 cardiac transplant recipients, measuring HLA antibody production every year after transplantation up to 13 years post‐transplant. Production of de novo DSA was analyzed in patients who had been negative for DSA prior to their transplant. DSA including transient antibodies were associated with poor patient survival (p = 0.0018, HR = 3.198). However, de novo and persistent DSA was strongly associated with poor patient survival (p = 0.0001 HR = 4.351). Although complement fixing persistent DSA correlated with poor patient survival, this was not increased compared to noncomplement fixing persistent DSA. Multivariable analysis indicated de novo persistent DSA to be an independent predictor of poor patient survival along with HLA‐DR mismatch and donor age. Only increasing donor age was found to be an independent risk factor for earlier development of CAV. In conclusion, patients who are transplanted in the absence of pre‐existing DSA make de novo DSA after transplantation which are associated with poor survival. Early and regular monitoring of post‐transplant DSA is required to identify patients at risk of allograft failure.     

The center effect in liver transplantation in the Eurotransplant region: a retrospective database analysis

Apart from donor and recipient risk factors, the effect of center‐related factors has significant impact on graft survival after liver transplantation (LT). To investigate this effect in Eurotransplant, a retrospective database analysis was performed, including all LT's in adult recipients (≥18 years) in the Eurotransplant region from 1.1.2007 until 31.12.2013. Additionally, a survey was sent out to all transplant centers requesting information on surgeons’ experience and exposure. In total, 10 265 LT's were included (median follow‐up 3.3 years), performed in 39 transplant centers. Funnel plots showed significant differences in graft survival between the transplant centers. After correction for donor and recipient risk, with the Eurotransplant donor risk index (ET‐DRI) and the simplified recipient risk index (sRRI) and random effects, these differences diminished. Mean historical volume (in the preceding 5 years) was a significant (P < 0.001), nonlinear marker for graft survival in the multivariate analysis. This study demonstrates that funnel plots can be used for benchmarking purposes in LT. Case‐mix correction can be performed with the use of the ET‐DRI and sRRI. The center effect encompasses the entire complex process of preoperative workup, operation to follow‐up.     

Long‐term survival in visceral transplant recipients in the new era: A single‐center experience

There is a paucity of data on long‐term outcomes following visceral transplantation in the contemporary era. This is a single‐center retrospective analysis of all visceral allograft recipients who underwent transplant between November 2003 and December 2013 with at least 3‐year follow‐up data. Clinical data from a prospectively maintained database were used to assess outcomes including patient and graft survival. Of 174 recipients, 90 were adults and 84 were pediatric patients. Types of visceral transplants were isolated intestinal transplant (56.3%), combined liver‐intestinal transplant (25.3%), multivisceral transplant (16.1%), and modified multivisceral transplant (2.3%). Three‐, 5‐, and 10‐year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3‐, 5‐, and 10‐year overall graft survival was 67%, 62%, and 61%, respectively. In multivariable analysis, significant predictors of survival included pediatric recipient (P = .001), donor/recipient weight ratio <0.9 (P = .008), no episodes of severe acute rejection (P = .021), cold ischemia time <8 hours (P = .014), and shorter hospital stay (P = .0001). In conclusion, visceral transplantation remains a good option for treatment of end‐stage intestinal failure with parenteral nutritional complications. Proper graft selection, shorter cold ischemia time, and improvement of immunosuppression regimens could significantly improve the long‐term survival.     

Kidney allograft failure in the steroid‐free immunosuppression era: A matched case‐control study

We studied the causes and predictors of death‐censored kidney allograft failure among 1670 kidney recipients transplanted at our center in the corticosteroid‐free maintenance immunosuppression era. As of January 1, 2012, we identified 137 recipients with allograft failure; 130 of them (cases) were matched 1‐1 for recipient age, calendar year of transplant, and donor type with 130 recipients with functioning grafts (controls). Median time to allograft failure was 29 months (interquartile range: 18‐51). Physician‐validated and biopsy‐confirmed categories of allograft failure were as follows: acute rejection (21%), glomerular disease (19%), transplant glomerulopathy (13%), interstitial fibrosis tubular atrophy (10%), and polyomavirus‐associated nephropathy (7%). Graft failures were attributed to medical conditions in 21% and remained unresolved in 9%. Donor race, donor age, human leukocyte antigen mismatches, serum creatinine, urinary protein, acute cellular rejection, acute antibody‐mediated rejection, BK viremia, and CMV viremia were associated with allograft failure. Independent predictors of allograft failure were acute cellular rejection (odds ratio: 18.31, 95% confidence interval: 5.28‐63.45) and urine protein ≥1 g/d within the first year post‐transplantation (5.85, 2.37‐14.45). Serum creatinine ≤1.5 mg/dL within the first year post‐transplantation reduced the odds (0.29, 0.13‐0.64) of allograft failure. Our study has identified modifiable risk factors to reduce the burden of allograft failure.     

National Outcomes of Liver Transplantation for Model for End‐Stage Liver Disease Score ≥40: The Impact of Share 35

In certain regions of the United States in which organ donor shortages are persistent and competition is high, recipients wait longer and are critically ill with Model for End‐Stage Liver Disease (MELD) scores ≥40 when they undergo liver transplantation. Recent implementation of Share 35 has increased the percentage of recipients transplanted at these higher MELD scores. The purpose of our study was to examine national data of liver transplant recipients with MELD scores ≥40 and to identify risk factors that affect graft and recipient survival. During the 12‐year study period, 5002 adult recipients underwent deceased donor whole‐liver transplantation. The 1‐, 3‐, 5‐ and 10‐year graft survival rates were 77%, 69%, 64% and 50%, respectively. The 1‐, 3‐, 5‐ and 10‐year patient survival rates were 80%, 72%, 67% and 53%, respectively. Multivariable analysis identified previous transplant, ventilator dependence, diabetes, hepatitis C virus, age >60 years and prolonged hospitalization prior to transplant as recipient factors increasing the risk of graft failure and death. Donor age >30 years was associated with an incrementally increased risk of graft failure and death. Recipients after implementation of Share 35 had shorter waiting times and higher graft and patient survival compared with pre–Share 35 recipients, demonstrating that some risk factors can be mitigated by policy changes that increase organ accessibility.     

Epstein‐Barr virus load in whole blood is associated with immunosuppression,but not with post‐transplant lymphoproliferative disease in stable adult heart transplant patients

Development of Epstein‐Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real‐time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty‐seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1–16.9) years post‐HTX]. In follow‐up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 ± 70.2 vs. 119.6 ± 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.     

An alternative approach to estimate age‐related mortality of kidney transplant recipients compared to the general population: results in favor of old‐to‐old transplantations

Compared to dialysis, kidney transplantation appears to be the best treatment for chronic kidney failure, even for older aged patients. Nevertheless, the individual benefit of transplanting elderly patients has to be balanced against the corresponding increase in the number of patients awaiting grafts. We analyzed the excess mortality related to kidney transplant recipients by taking into account the expected mortality of the general population (additive regression model for relative survival). We applied this method to a cohort of patients who received a first deceased‐donor kidney transplant between 1998 and 2009 in France (DIVAT, n = 3641). Overall 10‐year mortality was 13%. As expected, recipient age was the main risk factor associated with overall mortality. In contrast, recipient age was no longer significantly associated with the excess of mortality related to kidney transplant status by subtracting the expected mortality of the general population. Delayed graft function (DGF), pretransplantation immunization, and past history of diabetes appeared as the main risk factors of this higher mortality rate. Our results constitute a strong argument in favor of kidney transplantation, regardless of the patient's age. Preventing DGF may be more effective for decreasing the risk of death specifically attributable to the disease.     

Racial differences in incident de novo donor‐specific anti‐HLA antibody among primary renal allograft recipients: results from a single center cohort study

Controversy exists as to whether African American (AA) transplant recipients are at risk for developing de novo donor‐specific anti‐human leucocyte antigen (HLA) antibody (dnDSA). We studied 341 HLA‐mismatched, primary renal allograft recipients who were consecutively transplanted between 3/1999 and 12/2010. Sera were collected sequentially pre‐ and post‐transplant and tested for anti‐HLA immunoglobulin G (IgG) via single antigen bead assay. Of the 341 transplant patients (225 AA and 116 non‐AA), 107 developed dnDSA at a median of 9.2 months post‐transplant. AA patients had a 5‐year dnDSA incidence of 35%. This was significantly higher than the 5‐year dnDSA incidence for non‐AA patients (21%). DQ mismatch (risk) and receiving a living‐related donor (LRD) transplant (protective) were transplant factors associated with dnDSA. Within the AA patient cohort, HLA‐DQ mismatch, not‐receiving a LRD transplant, nonadherence and BK viraemia were the most common factors associated with early dnDSA (occurring <24 months post‐transplant). Nonadherence and pretransplant diabetes history were the strong precursors to late dnDSA. Despite the higher rates of dnDSA in the AA cohort, post‐dnDSA survival was the same in AA and non‐AA patients. This study suggests that DQ matching, increasing LRD transplantation in AA patients and minimizing under‐immunosuppression will be key to preventing dnDSA.     

Long‐term outcome of belatacept therapy in de novo kidney transplant recipients – a case‐match analysis

While belatacept has shown favorable short‐ and midterm results in kidney transplant recipients, only projections exist regarding its potential impact on long‐term outcome. Therefore, we performed a retrospective case‐match analysis of the 14 belatacept patients originally enrolled in the phase II multicenter trial at our center. Fifty six cyclosporine (CyA)‐treated patients were matched according to age at transplantation, first/retransplant, and donor type. Ten years after kidney transplantation, kidney function remained superior in belatacept‐treated patients compared with the CyA control group. Moreover, none of the belatacept‐treated patients had donor‐specific antibodies ≥10 years post‐transplantation compared with 38.5% of tested CyA‐treated subject (0/10 vs. 5/13; P = 0.045). Notably, however, patient and graft survival was virtually identical in both groups (71.4% vs. 71.3%; P = 0.976). In the present single‐center study population, patients treated with belatacept demonstrated a patient and graft survival at 10 years post‐transplant which was comparable to that of similarly selected CNI‐treated patients. Larger studies with sufficient statistical power are necessary to definitively determine long‐term graft survival with belatacept.     

Optimization of heart allocation: The transplant risk score

The new French heart allocation system is designed to minimize waitlist mortality and extend the donor pool without a detrimental effect on posttransplant survival. This study was designed to construct a 1‐year posttransplant graft‐loss risk score incorporating recipient and donor characteristics. The study included all adult first single‐organ recipients transplanted between 2010 and 2014 (N = 1776). This population was randomly divided in a 2:1 ratio into derivation and validation cohorts. The association of variables with 1‐year graft loss was determined with a mixed Cox model with center as random effect. The predictors were used to generate a transplant‐risk score (TRS). Donor‐recipient matching was assessed using 2 separate recipient‐ and donor‐risk scores. Factors associated with 1‐year graft loss were recipient age >50 years, valvular cardiomyopathy and congenital heart disease, previous cardiac surgery, diabetes, mechanical ventilation, glomerular filtration rate and bilirubin, donor age >55 years, and donor sex: female. The C‐index of the final model was 0.70. Correlation between observed and predicted graft loss rate was excellent for the overall cohort (r = 0.90). Hearts from high‐risk donors transplanted to low‐risk recipients had similar survival as those from low‐risk donors. The TRS provides an accurate prediction of 1‐year graft‐loss risk and allows optimal donor‐recipient matching.     

Living donor versus deceased donor liver transplantation: a surgeon‐matched comparison of recipient morbidity and outcomes

Informed consent for living donor liver transplantation (LDLT) requires that patients are provided with accurate information on the relative benefits and risks of this procedure compared with deceased donor liver transplantation (DDLT). There is strong evidence to suggest that LDLT facilitates timely transplantation to patients; however, information on the relative morbidity and death risks after LDLT as compared with DDLT is limited. A matched cohort comparison was performed matching recipients for age, MELD, date of transplant, gender, primary diagnosis, and recipient surgeon. A total of 145 LDLT were matched with 145 DDLT. LDLT had a higher overall rate of perioperative surgical complications (P = 0.009). Most of this difference was caused by a higher rate of biliary complications. However, the complications that occurred in the DDLT group tended to be more serious (P = 0.037), and these complications were strongly associated with graft loss in multivariate analysis. The 3‐ and 5‐year graft and patient survivals were similar. In conclusion, DDLT and LDLT have different complication profiles, but comparable hospital stays and survival rates. In areas of deceased donor organ shortages, LDLT offers an excellent alternative to DDLT because it facilitates access to a liver transplant without compromising short‐ or medium‐term recipient outcomes.     

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post‐transplant year

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long‐term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post‐transplant year (p = 0.655) but worse during the five subsequent years among the five‐yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post‐transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post‐transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non‐ALD recipients up to the fifth post‐transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre‐transplant diagnosis of ALD yields negative effects on post‐transplant outcomes beyond the fifth post‐transplant year, not attributable to recidivism.     

Economic Impacts of ABO‐Incompatible Live Donor Kidney Transplantation: A National Study of Medicare‐Insured Recipients

The infrequent use of ABO‐incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2‐incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3‐year posttransplant costs. The marginal costs of ABOi and A2i versus ABO‐compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death‐censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc ‐ year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long‐term dialysis and its associated morbidity and cost.     

Recipient age and outcome after pancreas transplantation: a retrospective dual-center analysis

With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.     

Genetic Variation in Caveolin‐1 Correlates With Long‐Term Pancreas Transplant Function

Pancreas transplantation is a successful treatment for a selected group of people with type 1 diabetes. Continued insulin production can decrease over time and identifying predictors of long‐term graft function is key to improving survival. The aim of this study was to screen subjects for variation in the Caveolin‐1 gene (Cav1), previously shown to correlate with long‐term kidney transplant function. We genotyped 435 pancreas transplant donors and 431 recipients who had undergone pancreas transplantation at the Oxford Transplant Centre, UK, for all known common variation in Cav1. Death‐censored cumulative events were analyzed using Kaplan–Meier and Cox regression. Unlike kidney transplantation, the rs4730751 variant in our pancreas donors or transplant recipients did not correlate with long‐term graft function (p = 0.331–0.905). Presence of rs3801995 TT genotype (p = 0.009) and rs9920 CC/CT genotype (p = 0.010) in our donors did however correlate with reduced long‐term graft survival. Multivariate Cox regression (adjusted for donor and recipient transplant factors) confirmed the association of rs3801995 (p = 0.009, HR = 1.83;[95% CI = 1.16–2.89]) and rs9920 (p = 0.037, HR = 1.63; [95% CI = 1.03–2.73]) with long‐term graft function. This is the first study to provide evidence that donor Cav1 genotype correlates with long‐term pancreas graft function. Screening Cav1 in other datasets is required to confirm these pilot results.     

High frequency of IL‐4 producing helper T lymphocytes associated with a reduced incidence of heart allograft rejection

Abstract The reduction in the frequency of rejection episodes several months after heart transplantation (HTX) correlates with the development of donor‐specific nonresponsiveness. This is reflected in a reduced frequency of donor‐specific cytotoxic T cells (CTL) in the peripheral blood. We investigated whether the reduced CTL frequency and the incidence of rejection episodes coincided with a change in the frequency of either IL‐2‐ or IL‐4‐producing helper T lymphocytes (HTL). We measured the frequency of HTL before and at several time points after HTX in the blood of ten recipients, using limiting dilution analysis for IL‐2 and IL‐4. In most patients, HTL frequencies dropped immediately after transplantation, but returned to pre‐HTX values later after transplantation. No consistent decrease or increase in frequencies was observed long after HTX. In contrast to IL‐2, the HTL frequencies for IL‐4 before transplantation were significantly higher in patients without post‐HTX rejection episodes requiring treatment than in patients with such episodes. This phenomenon was observed for the in vitro responses towards both donor and third‐party cells. In conclusion, relatively high frequencies of IL‐4‐producing T cells may have a beneficial effect on the outcome of human heart transplantation, because they are associated with a reduced incidence of rejection episodes after transplantation.