Death With A Functioning Graft Research Articles

Longevity Matching for Living Donor Renal Transplantation

This study identifies the effect of individual donor and recipient characteristics on graft survival in living-donor kidney transplantation (LDKT) using a recently described novel measure, kidney life years (KLYs). The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify first-time kidney-only LDKT recipients between 1987 and 2020 who did not experience death with a functioning graft (DWFG) and were not missing relevant information (n=87,290). Patient characteristics were evaluated using Cox and multiple regression analyses, with the dependent variable being KLYs. An equation for expected KLYs based on patient characteristics was created using regression coefficients. The equation was validated using bootstrapped Pearson correlations and then applied to the DWFG group for comparison. Based on statistical significance from Cox and multiple linear regression analyses, 9 of the original 18 variables were selected for inclusion in the equation. Variables with notable impact included HLA match points (0.021 KLYs; 95% CI: [0.019,0.024]; P ≤ .001), Donor Age (-0.030 KLYs; 95% CI: [-0.035,-0.025]; P ≤ .001), and Donor African American Ethnicity (-2.356 KLYs; 95% CI: [-2.552,-2.159]; P ≤ .001). Equation validation was supported, given a negative correlation (r=-0.071; P ≤ .001) between expected KLY change and observed graft failure. Expected KLY change was found to be greater in those who eventually DWFG when compared with all other LDKTs (t=-5.735, P ≤ .001). Increasing HLA match points may be more beneficial for graft longevity than minimizing donor age in comparisons using realistic between-donor differences. Additionally, greater average expected KLYs in those who ultimately DWFG may illustrate an opportunity for improved donor-recipient matching.

A single centre in-depth analysis of death with a functioning kidney graft and reasons for overall graft failure.

High numbers of unknown classifications and inconsistent methodologies in previous studies make the interpretation of causes leading to graft loss difficult. In addition, data on a holistic view looking at both death with a functioning graft (DWFG) and death-censored graft failure (DCGF) are sparse. In this single-centre study we included 1477 adult kidney transplants performed between 1997 and 2017, of which all 286 DWFGs until the end of observation were analysed and causes for death assigned. Additionally, the results were compared with the causes of 303 DCGFs of the same cohort to evaluate the impact of causes for overall graft loss. The most frequent causes for DWFG were cardiovascular disease (CVD) in 30.8%, malignancy in 28.3% and infections in 21%. Only 9.4% of reasons for DWFG were unknown. Sudden death occurred in 40% (35/88) of patients classified as DWFG due to CVD. Overall graft loss was related to the effect of immunosuppression in 36.2% [infection 20.9% (123/589), malignancy 15.3% (90/589)] and CVD in 22.4% (132/589). In 27.4% (161/589), graft failure was associated with underimmunosuppression (rejection). For infections (60 DWFG, 63 DCGF) and CVD (88 DWFG, 44 DCGF), a considerable overlap was observed between DWFG and DCGF. For patients >70years of age at transplantation, medical events accounted for 78% of overall graft losses and only 6.5% were associated with rejection. DWFG and DCGF share more causes for graft loss than previously reported and sudden death plays an underestimated role in death with a functioning graft.

Graft Failure Due to Nonadherence among 150 Prospectively-Followed Kidney Transplant Recipients at 18 Years Post-transplant: Our Results and Review of the Literature.

Background: We previously reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss in kidney transplantation. Here, among 150 prospectively-followed kidney transplant recipients at 18 years post-transplant, we provide: updated (longer-term) estimates of cause-specific graft loss probabilities, risk factors for developing GFNA, and detailed characterizations of patients’ overt nonadherent (NA) behavior, including timing, extent, and clinical consequences. Methods: Determination of the patient becoming NA in taking his/her immunosuppressive medications, and the underlying cause of graft loss, were determined prospectively by the attending physicians. For never-functioning-graft, GFNA, GF due to causes other than NA (Other GF), and death with a functioning graft (DWFG), cumulative incidence functions were used to estimate the cumulative probabilities of cause-specific graft loss. Cox stepwise regression was used to determine significant multivariable predictors for the hazard rate of developing GFNA. Results: GFNA was a major cause of graft loss (22/150 patients), particularly among African-American and Hispanic recipients <50 years of age-at-transplant (20/56 experienced GFNA), with estimated percentages of such patients ever developing GFNA ranging between 36.9 and 41.5%. These patients were also at a higher risk of developing Other GF. For the remaining patients (2/94 experienced GFNA), estimated percentages of ever-developing GFNA were much lower (range: 0.0–6.7%). The major cause of graft loss among recipients ≥50 years of age was DWFG; GFNA rarely occurred among older recipients. In 21/22 GFNA patients, NA behavior lasted continuously from the time of developing NA until GFNA. In total, 28/150 patients became NA, and 67.9% (19/28) occurred beyond 36 months post-transplant. A total of 25 of 28 NA patients (89.3%) developed biopsy-proven acute rejection and/or chronic rejection that was directly attributed to the NA behavior. Lastly, 25/28 admitted to NA behavior, with financial and psychological components documented in 71.4% (20/28) and 96.4% (27/28) of NA cases, respectively. Conclusions: These results highlight the importance of performing serial monitoring of patients for overt NA behavior throughout their post-transplant follow-up. Financial and psychological components to NA behavior need to be simultaneously addressed with the goal of achieving complete avoidance/elimination of NA behavior among higher risk patients.

Simultaneous pancreas-kidney transplantation in Caucasian versus African American patients: Does recipient race influence outcomes?

The influence of African American (AA) recipient race on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) is uncertain.MethodsFrom 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT.ResultsThe AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C‐peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P < .05). With a mean 9.2 year follow‐up, patient survival (65% C vs. 77% AA, P = .098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death‐censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P = .10). The incidence of death‐censored dual graft loss (usually rejection) was 7% C versus 21% AA (P = .005).ConclusionsFollowing SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG.

Death With Function and Graft Failure After Kidney Transplantation: Risk Factors at Baseline Suggest New Approaches to Management.

Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss. We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models. Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF. These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes-many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.

Early changes in renal resistive index and mortality in diabetic and nondiabetic kidney transplant recipients: a cohort study

BackgroundRenal resistive index (RI) predicts mortality in renal transplant recipients (RTR). However, its predictive value may be different according to the time of measurement. We analysed RI changes between 1 month and 3 months after transplantation and its predictive value for death with a functioning graft (DWFG).MethodsWe conducted a retrospective study in 1685 RTR between 1985 and 2017. The long-term predictive value of changes in RI value from 1 month to 3 months was assessed in diabetic and non-diabetic RTR.ResultsBest survival was observed in RTR with RI < 0.70 both at 1 and 3 months, and the worst survival was found in RTR with RI ≥ 0.70 both at 1 and 3 months (HR = 3.77, [2.71–5.24], p < 0.001). The risk of DWFG was intermediate when RI was < 0.70 at 1 month and ≥ 0.70 at 3 months (HR = 2.15 [1.29–3.60], p = 0.003) and when RI was ≥0.70 at 1 month and < 0.70 at 3 months (HR = 1.90 [1.20–3.03], p = 0.006).In diabetic RTR, RI was significantly associated with an increased risk of death only in those with RI < 0.70 at 1 month and ≥ 0.70 at 3 months (HR = 4.69 [1.07–20.52], p = 0.040). RI considered as a continuous variable at 1 and 3 months was significantly associated with the risk of DWFG in nondiabetic but not in diabetic RTR.ConclusionRI changes overtime and this impacts differently diabetic and nondiabetic RTR. RI short-term changes have a strong prognosis value and refines the risk of DWFG associated with RI.

P2B.19: Kidney Dysfunction after Intestinal Transplantation: Are We Headed in the Right Direction?

Introduction: Acute kidney injury (AKI) is a common complication after Intestinal transplantation (ITx). There are different etiologies for AKI: high Tacrolimus (TAC) levels, dehydration due to ostomy outputs and acute tubular necrosis (ATN) from sepsis, ischemia, and hemodynamic instability. Modifications in immunosuppressive regimen combined with surgical modifications may decrease the reported incidence of AKI. Methods: Retrospective analysis of 92 intestinal transplants from 2013–2017: 94.6% (87/92) received the colon. Induction: Thymoglobulin (2mg/kg x5) and Rituximab (150mg/m2 x1); maintenance: 42=TAC + Everolimus (EVL), 24=TAC + Sirolimus (SRL), 26=TAC alone. Target TAC levels: 10-15ng/ml:0–3 months (mo), 5-10ng/ml:3–6 mo, and 4-6ng/mL:> 6 mo. EVL or SRL started after 30 days with target trough levels of 3–5 ng/mL. AKI was defined by recipients who developed an increase in nadir creatinine and required hospitalizations. Estimated glomerular filtration rate (eGFR) was calculated from routine serum creatinine using the CKD-EPI formula for adults and bedside Schwartz formula for children. Median follow-up: 27 [3–56] mo. Results: AKI occurred in 26.1% (24/92) of Itx; 75% (18/24) in the first 6mo. Median eGFR at 2, 3, and 12 mo was 113.5 [85.0–151.4], 99.8 [65.1–131.0], and 97.3 [55.1–125.9], respectively. Operative time wasmarkedly reduced (median time: 288 minutes) as compared to previous eras. Median TAC levels (ng/ml) at 7days and at 1, 2, 3, and 12 mo: 10.6 [7.7–14.1], 10.9 [7.9–14.3], 8.5 [6.8–12.1], 7.5 [5.8–10.5], and 5.7 [7.9-4.0], respectively. Cox regression analysis of the hazard rate (HR) of developing AKI found 2 significant predictors: sepsis (23/92, P<.0001) and acute rejection (AR) (7/92, P<.0001). Similarly, the HR of developing an eGFR<60ml/min/1.73m2: older age at transplant (P<.0001), AR (7/92, P=.01), and dehydration on > 2 hospitalizations (17/92, P=.02). Intestinal graft failure (IGF) occurred in 9/92 patients; death with a functioning graft (DWFG) was observed in 12/92. Neither the development of an AKI nor an eGFR<60ml/min/1.73m2 were associated with the HR of developing graft loss (P>.10) or DWFG (P>.5). Conclusion: Short-term renal dysfunction post Itx still exists. Both surgical modifications and changes in the immunosuppressive regimen have led to diminished AKI and impact on graft failure. Long term follow-up is needed and underway.

Sleep apnea and kidney transplant outcomes: findings from a 20-year (1997–2017) historical cohort study

Objective/backgroundA historic cohort single-center study of kidney transplant recipients with graft loss examined the associations between sleep apnea and two transplant outcomes, death with a functioning graft (DWFG), and graft survival time. Patient/methodsAdult patients who received transplants and experienced graft failure or DWFG from January 1, 1997 to January 1, 2017 constituted the cohort (n = 322). Data for the study were obtained by merging two secondary data sources: the Organ Procurement and Transplantation Network (OPTN) database and the transplant center's medical records. A Cox regression modeled the association of diagnosed sleep apnea, stratified by year-of transplant surgery, with graft survival time. Using backward elimination, this model was adjusted for recipient age, race/ethnicity, gender, functional status, donor age, and antigen mismatch. ResultsNo statistically significant differences were found for proportions of DWFG in those with, versus without, sleep apnea, informing our censoring approach. When examining graft survival time, the Cox regression model was stratified given a sleep apnea and year-of-transplant interaction (p < 0.01, adjusted model). For patients transplanted between 1997 and 2008, sleep apnea was statistically significantly associated with a decreased risk of graft failure or cardiovascular-related DWFG [adjusted Hazard Ratio (aHR) = 0.63, 95%CI, 0.42–0.94]. For patients transplanted between 2009 and 2017, sleep apnea statistically significantly increased the risk of graft failure or cardiovascular-related DWFG (aHR = 2.61, 95%CI, 1.13–6.00). ConclusionsIn a cohort of transplant recipients with graft loss, sleep apnea increased the risk of graft loss nearly three-fold among patients transplanted between 2009 and 2017. Similar DWFG proportions by sleep apnea presence indicate this risk is likely driven by renal failure, not mortality. Further research on whether treatment of sleep apnea can improve graft survival is warranted.

The association between renal resistive index and premature mortality after kidney transplantation is modified by pre-transplant diabetes status: a cohort study.

Renal resistive index (RI) predicts mortality in renal transplant recipients, but we do not know whether this is true in diabetic patients. The objective of this study was to analyse the long-term predictive value of RI for death with a functioning graft (DWFG) in renal transplant recipients with or without pre-transplant diabetes. We conducted a retrospective study in 1800 renal transplant recipients between 1985 and 2017 who were followed for up to 30 years (total observation period: 14 202 patient years). Donor and recipient characteristics at time of transplantation and at 3 months were reviewed. The long-term predictive value of RI for DWFG and the age-RI and arterial pressure-RI relationships were assessed. A total of 284/1800 (15.7%) patients had diabetes mellitus before transplantation. RI was <0.75 in 1327/1800 patients (73.7%). High RI was associated with a higher risk of DWFG in non-diabetic patients [hazard ratio (HR) = 3.39, 95% confidence interval 2.50-4.61; P < 0.001], but not in patients with pre-transplant diabetes (HR = 1.25, 0.70-2.19; P = 0.39), even after multiple adjustments. There was no interaction between diabetes and age. In contrast, there was an interaction between RI and pulse pressure. Our study indicates that RI is not a predictor of DWFG in diabetic renal transplant recipients, in contrast to non-diabetic recipients. These findings could be due to a different age-RI or pulse pressure-RI relationship.

Patient's Death with a Functioning Graft is still the Most Common Cause of Kidney Transplant Loss

Introduction and Aims Kidney transplantation is the best and the most cost-effective modality of renal replacement therapy for patients with end stage chronic kidney disease. The mortality rate is higher in these patients than in general population, mainly caused by cardiovascular disease (CV). Death with a functioning graft (DWF) has increased over the decade, mitigating improvements in overall graft survival, probably due to older patient population with greater comorbidities who continue to have chronic immunosuppressive treatment. The ratio of mortality either by infectious or tumoral diseases has also highly increased. The causes of kidney allograft loss remain unclear. We investigated these causes in 1446 kidney transplant recipients. Our objective was to identify the main causes of mortality of renal transplant patients in our hospital. We described the global frequency of death with function (DWF), as well as the main causes of mortality in our patients. Methods It is a descriptive and transversal study in 1446 kidney transplant recipients followed-up in outpatient clinic, where frequency of death and most common causes were analyzed. Results During the follow-up, death with function (DWF) was the single most commonly observed cause of graft loss, 244 grafts,16,9% of all transplants. The frequency of death before discharge was 1.5% (N=22), before one year posttransplant 3.3% (N=48) and global mortality(16,9%)%)(N=244). The first cause of death was Cardiovascular(36,2%), followed by infections (22,3%) and malignancies(17,5%). There were no differences in the causes of death that occurred during the first year and more than 1 year posttransplant. 63,5% of the patients had at least one hospitalization after trasplantation, which 9,7% did at ICU. The most frequent maintenance for immunosuppressive regimen was tacrolimus+micofenolate (MMF)+prednisone (24,9%) The remaining functioning grafts were lost due to a variety of causes, including glomerular diseases (recurrent, transplant glomerulopathy, nonrecurrent) interstitial fibrosis/ tubular atrophy (IF/TA) and acute rejection (either celular or antibody-mediated). Conclusion Patient´s death with a functioning graft (DWF) has increased over the decade, mitigating improvements in overall graft survival, probably due to older patient population with greater comorbidities and it is still the most common cause of graft loss. Being the first cause of death cardiovascular, followed by infections, malignancies and others.

Deceased Donor Kidney Transplantation in Patients Aged 70 and Older: Is 70 the New 50?

Background: Deceased donor (DD) kidney transplantation (KT) outcomes in patients who are aged 70 years and older are understudied. Methods: We retrospectively reviewed our single center DD KT outcomes in patients aged 70 years and older. All patients received antibody induction with tacrolimus, half-dose mycophenolate, ± steroids. Results: Over 10.75 years, we performed 114 KTs in 112 patients aged 70 and older (mean 73.8, range 70-84 years) including 42 patients who were aged 75 and older. The study group included 60 males/52 females and 79 Caucasians/28 African Americans/5 other with a mean waiting time of 16 months; 75 patients (66%) received kidneys from expanded criteria donors (ECDs) and 14 received dual KTs. Delayed graft function occurred in 27% and influenced graft but not patient survival. With a mean follow-up of 68 months, patient survival was 59% and uncensored kidney graft survival was 47%. Three year and death-censored kidney graft survival rates were 76% and 74%, respectively. Outcomes were similar in patients < or ≥ 75 years. Of 60 graft losses, death with a functioning graft (DWFG) accounted for 41 (68%). Of 46 deaths, 72% were due to cardio/cerebrovascular events, infection, or malignancy. At present, 54 of the 66 surviving patients (81.8%) have functioning grafts. The incidences of acute rejection and major infection were 14% and 45%, respectively. Conclusions: Advanced recipient age has a modest effect on medium-term outcomes in appropriately selected elderly patients using predominantly ECD kidneys, which may not be appropriate for younger patients. However, medium-term outcomes are largely influenced by a higher incidence of DWFGs in the elderly, suggesting that matching strategies for kidney and patient longevity are warranted.

Reduced rate of cardiovascular death after cytomegalovirus prophylaxis in renal transplant recipients.

It is unknown how death with a functioning graft (DWFG) is affected in renal transplant recipients who receive prophylaxis for cytomegalovirus (CMV) infection. Data from 61,927 adult recipients of a deceased donor kidney transplant in 1990 to 2012 registered with the Collaborative Transplant Study were analyzed. Cytomegalovirus prophylaxis was administered in 18%, 75%, 27% and 34% of R-/D- (recipient-negative, donor-negative), R-/D+, R+/D- and R+/D+ transplants, respectively. Only in R-/D+ transplants was CMV prophylaxis associated with significantly improved patient survival versus no prophylaxis (P<0.001). Unexpectedly, in the R-/D+ subgroup, DWFG because of infection was not significantly affected by use of CMV prophylaxis (P=0.16) but death from cardiovascular disease was significantly lower (P<0.001). Cox regression analysis confirmed that the primary impact of CMV prophylaxis on DWFG in R-/D+ transplants was because of reduced cardiovascular death (hazard ratio, 0.66; 95% confidence interval, 0.51-0.85; P=0.002), an effect restricted to patients aged 40 years or older (hazard ratio, 0.61; 95% confidence interval, 0.46-0.81; P<0.001). We conclude that CMV prophylaxis is associated with a significant benefit for risk of cardiovascular DWFG among R-/D+ kidney transplant patients aged ≥ 40 years. Cytomegalovirus prophylaxis appears particularly critical in this patient subpopulation.

Single-centre study of 628 adult, primary kidney transplant recipients showing no unfavourable effect of new-onset diabetes after transplant.

To better understand the implications of new-onset diabetes after transplant (NODAT), we used our prospectively followed cohort of 628 adult primary kidney transplant recipients to determine the prognostic impact of pretransplant diabetes and NODAT. The study cohort consisted of all participants in four randomised immunosuppression trials performed at our centre since May 2000. For each cause-specific hazard analysed, Cox stepwise regression was used to determine a multivariable model of significant baseline predictors; the multivariable influence of having pretransplant diabetes and NODAT (t) (the latter defined as a zero-one, time-dependent covariate) was subsequently tested. Similar analyses of estimated glomerular filtration rate (eGFR) at 36 and 60 months post transplant were performed using stepwise linear regression. Finally, a repeated measures analysis of mean HbA1c as a function of diabetes category (pretransplant diabetes vs NODAT) and randomised trial (first to fourth) was performed. Median follow-up was 56 months post transplant. Patients with pretransplant diabetes comprised 23.4% (147/628), and 22.5% (108/481) of the remaining patients developed NODAT. Pretransplant diabetes had no prognostic influence on first biopsy-proven acute rejection and death-censored graft failure hazard rates, nor on eGFR, but was associated with significantly higher rates of death with a functioning graft (DWFG) (p = 0.003), DWFG due to a cardiovascular event (p = 0.005) and infection that required hospitalisation (p = 0.03). NODAT (t) had no unfavourable impact on any of these hazard rates nor on eGFR, with actuarial freedom from DWFG remaining at over 90% among patients in pre- and post-NODAT states at 72 months post transplant/NODAT. Mean HbA1c for patients in the first to fourth randomised trials, averaged across diabetes category, decreased by trial (7.28%, 6.92%, 6.87% and 6.64% [56.1, 52.1, 51.6 and 49.1 mmol/mol], respectively; p = 0.02). Less-than-expected post-NODAT risk for graft loss and death may exist in the current climate of tighter glucose monitoring post transplant.

Expanded Criteria Donors: The End of an Era.

Expanded criteria donor (ECD) kidneys increase the donor organ pool but their value has been questioned because of expected lower survival outcomes. With the development of the Kidney Donor Risk Index and a new allocation system, the end of the ECD kidney era is imminent. The study purpose was to retrospectively review our 12 year single center experience with ECD kidney transplants (KT). Methods: All patients (pts) received antibody induction with tacrolimus/mycophenolate ± steroids. Standardized management algorithms were implemented to preserve nephron function (including machine preservation) and pt selection was based on low immunological risk and predicted limited nephron need. Results: Over a 12 year period, we performed 1366 deceased donor KTs in adult pts including 468 (34%) from ECDs; 245 pts (53%) had at least 5 years follow-up. 36 KTs were from DCD/ECDs and 46 dual KTs were performed. With a mean follow-up of 4 years, actual pt survival was 75% and graft survival was 59%. 75 pts (16%) experienced death with a functioning graft (DWFG), so death-censored graft survival was 70%. One year pt and graft survival were 94% and 86%. Outcomes were analyzed according to recipient age categories (<50, n=70; 50-59, n=116; 60-69, n=185; >70, n=95). The incidence of primary nonfunction was slightly higher in the oldest and youngest (6%) compared to the 2 mid-age recipient categories (4%, p=NS). DWFGs were significantly higher in the oldest (22%) compared to the youngest recipient category (8.6%, p=0.03), whereas the incidence was intermediate (16%) in the 2 mid-age categories. One-year mortality was also higher in the oldest (9.5%) compared to the three younger recipient age categories (4.9%, p=0.09). Overall mortality rates increased with older age category from 19% in youngest to 28% in oldest recipients (p=NS). One year rates of graft loss were 12.3% in the 2 younger compared to 15% in the 2 older categories (p=NS). However, the overall rate of graft loss was 47% in the youngest compared to 40% in the 3 older categories (p=NS). Conclusions: By appropriate donor and recipient profiling and the use of management algorithms aimed at preserving renal function, acceptable intermediate-term outcomes can be achieved with ECD KTs irrespective of recipient age.

Systematic Study of Causes of Death and Allograft Loss After Pancreas Transplantation in the Modern Era.

Background: The aim of the study is to identify specific causes of mortality and pancreas allograft loss of the three pancreas transplantation (PT) types in the modern era with ATG induction and tacrolimus based triple immunosuppression. Methods: We performed a retrospective review of 262 adult patients who received PT at our institution from 01/01/1998 to 12/31/2009. The causes of death and graft loss were determined by reviewing clinical and histologic information. Results:89 recipients from the cohort died during the median follow-up of 8 years (IQR 4.1 to 11.2 years). The most common causes of death were infection/sepsis (20%) and cardio/cerebrovascular disease (25 %). Among patients that died, the cause of death was not different among the three PT types (p=0.50). 133 of 279 (48%) grafts were lost, and 10 recipients (4%) lost more than one allograft. Graft losses due to death with a functioning graft (DWF)(37%) and graft thrombosis (17% early and 7% late) were the most common causes. Within the first year post PT, early thrombosis was the most common cause of all graft loss (53%). Immunologic factors became most common causes censoring for death beyond one year post PT (50%). Graft survival was higher in Simultaneous Pancreas Kidney transplantation (SPK) than that in Pancreas transplantation alone (PTA) or Pancreas after kidney transplantation (PAK) recipients, most likely because of the relative low incidence of DWF and graft loss due to immunologic factors in SPK recipients. Conclusion: PT may not change the distribution of underlying causes of death in patients with long-standing diabetes. Early thrombosis and rejection remain the main targets in our efforts to improve long term pancreas allograft survival.

Association of HLA Mismatch With Death With a Functioning Graft After Kidney Transplantation: A Collaborative Transplant Study Report

HLA mismatches may correlate with risk of death with a functioning graft (DWFG) because of requirement for higher immunosuppression doses and more antirejection therapy. Deceased-donor kidney transplants (n = 177 584) performed 1990-2009 and reported to the Collaborative Transplant Study were analyzed. The incidence of DWFG was found to be 4.8% during year 1 posttransplant and 7.7% during years 2-5 (Kaplan-Meier estimates). Most frequent causes of DWFG were infection, cardiovascular disease and malignancy (32.2%, 30.9% and 3.6% in year 1; 16.4%, 29.6% and 15.9% in years 2-5). HLA-A + B + DR mismatches were significantly associated with DWFG during year 1 (p < 0.001), a correlation that diminished but persisted during years 2-5 (p < 0.001). HLA mismatch was associated with DWFG because of infection (p < 0.001 during year 1, p = 0.043 during years 2-5) or cardiovascular disease (p < 0.001 during year 1, p = 0.030 during years 2-5) but not malignancy. There was also a significant association between HLA mismatch and hospitalization for viral (p < 0.001) or bacterial (p = 0.002) infection. Multivariable analysis showed that mismatches for HLA class II were more strongly associated with both hospitalization and DWFG than mismatches for HLA class I.

Causas de muerte en pacientes con un injerto renal funcionante: ¿Han ocurrido cambios en las últimas décadas?

Death with a functioning graft (DWGF) is now one of the main causes of renal transplant (RTx) loss. To determine whether the causes of DWGF, characteristics of donors and recipients and complications of RTx have changed in the last two decades. Cooperative study of a cohort of 418 kidney grafts performed between 1968 and 2010. Patients were divided into two groups according to whether their kidney transplants were performed between 1968 and 1992 (Group 1) or 1993 and 2010 (Group 2). Sixty eight patients experienced DWGF. Infections were the leading cause of DWGF in both groups (38 and 41%, respectively), followed by cardiovascular diseases (24 and 23% respectively), gastrointestinal disorders (21 and 26% respectively) and cancer (17 and 10% respectively). There were no significant differences in causes of death between the two groups according to the time elapsed since the renal transplantation. In patients in Group 1, the interval between diagnosis of renal failure and dialysis (HD) and the interval between the start of HD and kidney transplantation were significantly lower than in Group 2. The former had also an increased number of acute rejections in the first five years of kidney transplantation (p < 0.001). In Group 2, patients more often received their kidneys from deceased donors, had previous kidney transplantation, higher rate of antibodies to a panel of lymphocytes and an increased incidence of cardiovascular disorders after five years of RTx. The proportion of graft loss due to DWGF has increased over the last 2 decades, but its causes have not changed significantly. Infections are the most common causes of DWGF followed by cardiovascular and digestive diseases.

653: Death with a Functioning Graft after Lung Transplantation: Lessons from the Kidney

Death with a functioning graft (DWF) has been reported as a major cause of secondary graft loss after renal transplantation with an incidence of 9-30%. However, DWF is rarely reported after lung or heart-lung transplantation where obliterative bronchiolitis (OB), manifesting as the bronchiolitis obliterans syndrome (BOS) is the principal cause of graft loss and death. Our aim was to assess the incidence and etiology of DWF after lung transplantation (LTx).

A Cause-Specific Hazard Rate Analysis of Prognostic Factors Among 877 Adults Who Received Primary Orthotopic Liver Transplantation

In orthotopic liver transplantation (OLT) distinct causes of graft failure (GF) and death with a functioning graft (DFG) exist. Prognostic factors for one failure type may be distinctly different from those predictive of other types, and an accurate portrayal of these relationships may more clearly explain each factor's importance. A multivariable cause-specific hazard (CSH) rate analysis using Cox stepwise regression was performed among 877 adults who received primary OLT during 1996-2004 with tacrolimus+steroids as immunosuppression. Older donor age (P=0.004) implied greater primary dysfunction GF, while primary sclerosing cholangitis (PSC; P=0.0002) implied greater vascular thrombosis GF. Recurrent nonmalignant liver disease GF was higher among hepatitis C virus patients (P<0.00001), and younger recipient age (P=0.005) implied greater death from recurrent (metastatic) hepatocellular carcinoma. African-American race (P<0.00001), PSC (P=0.003), and younger recipient age (P=0.005) were independently associated with greater GF due to chronic rejection. Older donor age (P=0.003) implied greater infection DFG, while older recipient age (P=0.003) and pretransplant diabetes (P=0.03) were independently associated with greater cardiovascular/cerebrovascular DFG. Finally, most of these cause-specific predictors were not significant in an overall Cox model for graft survival. The CSH approach should be more widely used in investigations of prognostic factors. The result of older donor age implying greater primary dysfunction GF and infection DFG but having no association with other failure types demonstrates that its impact is specific to the graft's early posttransplant functional status. In addition, while recipient age was an important prognosticator, its direction of association reverses depending upon the outcome being analyzed.

Death with Functioning Graft in Living Donor Kidney Transplantation: Analysis of Risk Factors

Background: Death with a functioning graft (DWF) has been reported as a major cause of graft loss after renal transplantation. It has been reported to occur in 9–30%. Methods: From March 1976 to January 2002, a total of 1,400 living donor renal transplants were performed in our center. Out of 257 reported deaths among our patients, 131 recipients died with functioning grafts after a mean period of 53.4 ± 53.2 months. Results: DWF patients account for 27% of all graft losses in our series. The mean age was 34.9 + 10.6 (range 8–62 years), 98 of them were male and 33 were female. The original kidney disease was GN in 9, PN in 24, PCK in 5 and nephrosclerosis in 8 patients. Acute rejection episodes were diagnosed in 84 patients (63.1). The post-transplant complications encountered were hypertension in 78 patients (59.5%), diabetes mellitus in 30 patients (22.9%), medical infections in 68 (51.5%), hepatic complications in 30 (22.9%) and malignancy in 17 patients (13%). The main causes of death in these patients were infections in 46 (35.6%), cardiovascular in 23 (17.6%), liver cell failure in 15 patients (11.4%) and malignancy in 8 (6.1%). The mean serum creatinine was 2 ± 0.6 mg/dl at last follow-up before death. Conclusion: We conclude that the relatively higher mortality in renal transplantation is, in part, due to co-morbid medical illness, pre-transplant dialysis treatment, and factors uniquely related to transplantation, including immunosuppression and other drug effects. DWF must be in consideration when calculating graft survival.