Deceased Donor Kidney Transplant Recipients Research Articles

Is Lack of Consensus on the Management of Chronic Active Antibody-Mediated Rejection Harming Renal Transplant Recipients?

In 2022, over 92,000 kidney transplants were performed globally. With advancements in transplant science, 1-year graft survival rates have reached 94.3% for deceased donor kidney transplant recipients, and 97.8% for living recipients. However, 5-year graft survival remains at 76.3% and 86.5%. Antibody-mediated rejection (AMR) is one of the most common causes of immune-related allograft rejection. Chronic active AMR (CABMR) typically develops 6–12 months post-transplant; 76% of kidney transplant recipients with CABMR experience graft loss 1.9 years after diagnosis. Despite these alarming figures, consensus guidelines on the management of post-transplant patients have not been updated with advancements in testing and protocol biopsies, and there is currently no consensus in Europe on CABMR management.

Ensemble Clustering to Generate Phenotypes of Kidney Transplant Donors and Recipients.

In this paper we investigate the generation of phenotypes for kidney transplant donors and recipients to assist with decision making around organ allocation. We present an ensemble clustering approach for multi-type data (numerical and categorical) using two different clustering approaches-i.e., model based and vector quantization based clustering. These clustering approaches were applied to a large, US national deceased donor kidney transplant recipient database to characterize members of each cluster (in an unsupervised fashion) and to determine whether the subsequent risk of graft failure differed for each cluster. We generated three distinct clusters of recipients, which were subsequently used to generate phenotypes. Each cluster phenotype had recipients with varying clinical features, and the risk of kidney transplant graft failure and mortality differed across clusters. Importantly, the clustering results by both approaches demonstrated a significant overlap. Utilization of two distinct clustering approaches may be a novel way to validate unsupervised clustering techniques and clustering can be used for organ allocation decision making on the basis of differential outcomes.

Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.

The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty. We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age. Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days. The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.

Tacrolimus Interaction with Azole Antifungals in Kidney Transplant Recipients: Is Fluconazole or Clotrimazole a Worse Offender?

The utilization of rabbit ant thymocyte globulin induction with tacrolimus-based maintenance immunosuppression may increase the risk for opportunistic fungal infections, particularly oral-esophageal candidiasis. Both are commonly prescribed for deceased donor kidney transplant recipients Tacrolimus (TAC), a calcineurin inhibitor, is metabolized hepatically by cytochrome P450 3A4/5 enzymes. Due to this, a drug interaction can occur with TAC and either fluconazole (FCZ) or clotrimazole (CTMZ). Both are commonly used for antifungal prophylaxis. While both FCZ and CTMZ inhibit CYP3A4/5, systemic absorption of CTMZ is minimal, theoretically limiting the interaction with TAC and reducing the need for dose readjustments. Medical records for adult patients receiving a renal transplant between March 2009 and September 2011 were retrospectively reviewed for TAC dose adjustments following discontinuation of the antifungal agent required to maintain therapeutic TAC blood levels. The change in TAC dose: trough ratio 4-8 weeks after azole discontinuation was greater in patients receiving FCZ compared to CTMZ (FCZ +92.9% vs CTMZ +43.4%, p=0.004). In addition, the proportion of patients requiring ≥30% TAC dose increase was 70% with FCZ versus 45% with CTMZ (p=0.006). The choice of antifungal also did not affect the number of sub-therapeutic TAC levels, the number of patients with sub-therapeutic levels pre- or post-discontinuation, or incidence of biopsy-proven allograft rejection.

The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.

Re-assessing prolonged cold ischemia time in kidney transplantation through machine learning consensus clustering.

We aimed to cluster deceased donor kidney transplant recipients with prolonged cold ischemia time (CIT) using an unsupervised machine learning approach. We performed consensus cluster analysis on 11615 deceased donor kidney transplant patients with CIT exceeding 24h using OPTN/UNOS data from 2015 to 2019. Cluster characteristics of clinical significance were identified, and post-transplant outcomes were compared. Consensus cluster analysis identified two clinically distinct clusters. Cluster 1 was characterized by young, non-diabetic patients who received kidney transplants from young, non-hypertensive, non-ECD deceased donors with lower KDPI scores. In contrast, the patients in cluster 2 were older and more likely to have diabetes. Cluster 2 recipients were more likely to receive transplants from older donors with a higher KDPI. There was lower use of machine perfusion in Cluster 1 and incrementally longer CIT in Cluster 2. Cluster 2 had a higher incidence of delayed graft function (42%vs. 29%), and lower 1-year patient (95%vs. 98%) and death-censored (95%vs. 97%) graft survival compared to Cluster 1. Unsupervised machine learning characterized deceased donor kidney transplant recipients with prolonged CIT into two clusters with differing outcomes. Although Cluster 1 had more favorable recipient and donor characteristics and better survival, the outcomes observed in Cluster 2 were also satisfactory. Overall, both clusters demonstrated good survival suggesting opportunities for transplant centers to incrementally increase CIT.

A2/A2B to B deceased donor kidney transplantation in the Kidney Allocation System era

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.192.332.47; P < .001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.780.941.13, P = .5). Moreover, there was no difference between A2→B vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.771.001.29, P > .9) or all-cause graft loss (wHR 0.820.961.12, P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.

Duration of Dialysis in Acute Kidney Injury Donors and Transplant Outcomes.

Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited. This was a single-center study of deceased donor kidney transplants from 2010 to 2022. The study cohort consisted of recipients of deceased donor kidney transplants from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: 1 to 2 dialysis days, 3 to 4 dialysis days, and 5 or more dialysis days. During this period, 765 AKI deceased donor transplants were performed, of which 230 were from donors on dialysis. The median dialysis duration was 2 days with a maximum of 13 days. Across the 3 groups, there were no differences in recipient age (p = 0.23) or dialysis vintage (p = 0.70). Donor age (p = 0.86) and kidney donor profile index (p = 0.57) were comparable between the groups. Recipients of deceased donor kidney transplants from donors on dialysis 5 or more days had lower terminal creatinine levels (p = 0.003) and longer cold ischemia times (p = 0.04). Posttransplant, the median length of hospital stay was 3 days for all groups (p = 0.75). There were no differences in delayed graft function occurrence (94.4% vs 86.8% vs 92.1%, p = 0.19), duration of delayed graft function (p = 0.56), or readmissions (p = 0.99). At 1 year posttransplant, the estimated glomerular filtration rate (p = 0.76), patient survival (p = 0.82), or death-censored graft survival (p = 0.28) were comparable. Excellent outcomes have been observed in AKI deceased donor kidney transplants, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. In total, 99543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

89 Frailty in Renal Transplantation: Retrospective Cohort Study to Examine the Impact of the New 2019 Kidney Offering Scheme on Older Transplant Recipients

Abstract Background In 2019, a new kidney offering scheme was launched in the United Kingdom, aiming to better match estimated patient survival and graft life expectancy. The impact of the scheme on older patients undergoing kidney transplantation (KT) is unknown. Aim This study aims to compare outcomes of elderly KT recipients before and after the introduction of the 2019 kidney offering scheme. Method A retrospective cohort study of two groups of elderly patients who underwent KT was undertaken. Group 1 included patients transplanted between 01/09/2017 and 31/08/2019 as part of the “2006 allocation scheme”. Group 2 included patients transplanted between 01/09/2019 and 31/08/2021 as part of the “2019 offering scheme”. An elderly patient was defined as any person over 60 years of age at the time of KT. Univariate binary logistic regression analysis was performed to determine odds ratios (OR) and 95% confidence intervals. Results There were 107 elderly deceased donor KT recipients; 62 from Group 1 and 45 from Group 2. The median age at transplantation was 68 years (62-71) and 67 years (64-73), respectively. Univariate analysis showed that level four HLA mismatch (OR 4.667 95%CI 1.640-13.275, p = 0.004) and a requirement for re-intervention (OR 6.496 95%CI 1.306-32.216, p = 0.022) were significantly more likely in the 2019 offering scheme. One year graft survival worsened on introduction of the 2019 offering scheme (85% vs 80%). Conclusions The introduction of the 2019 offering scheme has led to less favourable HLA matches, increased need for reintervention, and a lower one-year graft survival in elderly KT recipients.

Delayed Graft Function Among Kidney Transplant Recipients Is Associated With an Increased Risk of Urinary Tract Infection and BK Viremia.

Delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs) is a well-known risk factor for allograft rejection, decreased graft survival, and increased cost. Although DGF is associated with an increased risk of rejection, it is unclear whether it also increases the risk of infection. We reviewed all adult DDKTRs at our center between 2010 and 2018. The primary outcomes of interest were BK viremia, cytomegalovirus viremia, pneumonia, and urinary tract infection (UTI) within the first year of transplant. Additional analysis was made with censoring follow-up at the time of allograft rejection. A total of 1512 DDKTRs were included, of whom 468 (31%) had DGF. As expected, several recipient, donor, and baseline immunological characteristics differed by DGF status. After adjustment, DGF was significantly associated with an increased risk of BK viremia (hazard ratio: 1.34; 95% confidence interval, 1.0-1.81; P = 0.049) and UTI (hazard ratio: 1.70; 95% confidence interval, 1.31-2.19; P < 0.001) but not cytomegalovirus viremia or pneumonia. Associations were similar in models censored at the time of rejection. DGF is associated with an increased risk of early infectious complications, mainly UTI and BK viremia. Close monitoring and appropriate management are warranted for better outcomes in this unique population.

Predicting 5-year survival after kidney transplantation in Colombia using the survival benefit estimator tool.

A complex relationship between donor and recipient characteristics influences kidney transplant (KT) success. A tool developed by Bae S. et al. (Survival Benefit Estimator, SBE) helps estimate post-KT survival. We aim to evaluate the predictive performance of the SBE tool in terms of 5-year patient survival after a kidney transplant. A retrospective cohort study of all deceased-donor KT recipients between January 2009 to December 2021. A descriptive analysis of clinical and sociodemographic characteristics was performed. The SBE online tool was used to calculate the predicted patient survival (PPS) and the survival benefit at five years post-KT. Comparisons between predictive vs. actual patient survival were made using quintile subgroups. Three Cox regression models were built using PPS, EPTS, and KDPI. A total of 1145 recipients were evaluated. Mortality occurred in 157 patients. Patient survival was 86.2%. Predictive survival for patients if they remained on the waiting list was 70.6%. The PPS was 89.3%, which results in a survival benefit (SB) of 18.7% for our population. Actual survival rates were lower than the predicted ones across all the quintiles. In unadjusted analysis, PPS was a significant protective factor for mortality (HR 0.66), whereas EPTS (HR 8.9) and KDPI (HR 3.25) scores were significant risk factors. The discrimination of KDPI, PPS, and EPTS scores models were 0.59, 0.65, and 0.66, respectively. SBE score overestimated actual survival rates in our sample. The discrimination power of the score was moderate, although the utility of this tool may be limited in this specific population.

Influence of donor sex and age on graft outcome in kidney transplantation.

There is a known recipient sex-dependent association between donor sex and kidney transplant survival. We hypothesized that donor age also modifies the association between donor sex and graft survival. First, deceased donor kidney transplant recipients (1988-2019, n=461364) recorded in the Scientific Registry of Transplant Recipients, the Australia and New Zealand Dialysis and Transplant Registry and the Collaborative Transplant Study were analyzed. We used multivariable Cox regression models to estimate the association between donor sex and death censored graft loss, accounting for the modifying effects of recipient sex and donor age; donor age was categorized as 5-19, 20-34, 35-49, 50-59 and ≥60years. Results from cohort-specific Cox models were combined using individual patient data meta-analysis. Among female recipients of donors aged <60years, graft loss hazards did not differ by donor sex; recipients of female donors ≥60years showed significantly lower graft loss hazards than recipients of male donors of the same age [combined adjusted hazard ratio (aHR) 0.90, 95% CI 0.86-0.94]. Among male recipients, female donors aged <50years were associated with significantly higher graft loss hazards than same-aged male donors (5-19years: aHR 1.11, 95% CI 1.02-1.21; 20-34years: aHR 1.08, 95% CI 1.02-1.15; 35-49years: aHR 1.07, 95% CI 1.04-1.10). There were no significant differences in graft loss by donor sex among male recipients of donors aged ≥50years. Donor age modifies the association between donor sex and graft survival. Older female donors were associated with similar or lower hazards of graft failure than older male donors in both male and female recipients, suggesting a better functional reserve of older female donor kidneys.

Pregnancy after deceased donor vs living donor kidney transplant: associated obstetric and graft outcomes

Outside of pregnancy, deceased donor kidney transplant recipients experience worse graft and overall survival compared to living donor kidney transplant recipients. In pregnancy, it is unknown whether the type of donor graft modifies either graft health in the peripartum period or pregnancy outcomes. The objective of this study was to define characteristics and outcomes in pregnancy based on donor type in kidney transplant recipients. Retrospective cohort study of adult kidney transplant recipients who received their graft between 2000-2019 with a subsequent pregnancy enrolled in the Transplant Pregnancy Registry International. The primary outcome was graft loss within 2 years of delivery. Secondary outcomes included severe maternal morbidity and neonatal composite morbidity. Univariate, multivariable logistic regression, and Cox proportional-hazards models were constructed for statistical analysis, with living unrelated donor recipients as the referent. 638 pregnancy outcomes after kidney transplant met our inclusion criteria. Of these, 168 (26.3%) received a graft from a deceased donor (DD), 310 (48.6%) from a living related donor (LR), and 160 (25.1%) from a living unrelated donor (LU). DD recipients were more likely to be nulliparous, have an unplanned pregnancy, and self-identify as non-white. DD recipients were more likely to experience urinary tract infections (DD: 21.8%; LR: 10.1%; LU: 20.6%) (p=0.018). Severe maternal morbidity did not differ by donor type (DD: 3.4%; LR: 2.8%; LU: 7.2%), nor did neonatal composite morbidity (DD: 8.4%, LR: 17.1%, LU: 14.4%). DD transplant was associated with graft loss within 2 years of delivery (DD: 6.7%, LR: 3.7%, LU: 1.3%, aOR: 7.52 [1.53, 60.8]) and long-term graft loss from transplant (aHR: 2.08, [1.10, 3.95]). While our study demonstrates an association between deceased donor transplant and graft loss after pregnancy, it does not provide evidence that pregnancy itself causes graft loss. Deceased donor kidney transplant recipients should not be discouraged from pursuing pregnancy based on their donor type, but these patients should undergo preconception counseling with a discussion of their individualized obstetric and graft risks, close intrapartum monitoring for infection and hypertensive disease, and continued surveillance for at least 2 years postpartum with a multidisciplinary obstetrics and transplant team.

Excellent efficacy and beneficial safety during observational 5-year follow-up of rapid steroid withdrawal after renal transplantation (Harmony FU study).

We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P=.041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).

Outcomes After Deceased Donor Kidney Transplantation Using Kidney Allografts With Marginal Perfusion Parameters

This study examines outcomes of deceased donor kidney transplantation (DDKT) in recipients of kidney allografts with marginal perfusion parameters. Allografts with marginal perfusion parameters (resistance index [RI] >0.4 and pump flow rate [F] <70 mL/min; MP group) were compared with those with good parameters (RI <0.4 and F >70 mL/min; GP group) for DDKT recipients between January 1996 and November 2017 after hypothermic pulsatile perfusion. Demographics, creatinine, cold ischemia times (CIT), delayed graft function (DGF), and recipient glomerular filtration rate at pre- and post-transplant were noted. The primary outcome was graft survival post-transplant. In the MP (n=31) versus GP (n=1281) group, the median recipient was aged 57 years versus 51 years; the median donor was aged 47 versus 37 years; terminal creatinine was 0.9 versus 0.9 mg/dL; CIT was 10.2 versus 13 hours, and the RI and flow were 0.46 and 60 mL/min versus 0.21 and 120 mL/min. The DGF rate was 19% (MP) versus 8% (GP). The graft survival in the MP versus GP group was 81% versus 90% (1 year), 65% versus 79% (3 years), 65% versus 73% (4 years), and 45% versus 68% (5 years). Carefully selected kidney allografts after comprehensive donor and recipient evaluation may allow for the use of these routinely discarded kidneys with marginal perfusion parameters.

#5999 GRADES II-III INTRA-ABDOMINAL HYPERTENSION INCREASE THE RISK OF GRAFT LOSS OR DEATH AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Intra-abdominal hypertension (IAH) is common among post-surgical, critically ill and kidney transplant patients, and is associated with acute kidney injury and increased morbidity and mortality. We aimed to describe the medium-term effect of IAH on graft and patient survival after deceased-donor kidney transplantation. Method 192 consecutive patients who received a cadaveric renal allograft transplant at our hospital were included in this study. IAP was measured every 8h for at least the first 72h after surgery using the urinary bladder technique, and an average value was obtained. Patients were followed up for 24 months or until a composite outcome (defined as graft loss or recipient death) occurred. Clinical, anthropometric, and analytical data was extracted from our hospital's database. Statistical analysis was performed using IBM SPSS Statistics 22. The study was approved by the local ethics committee. Results 192 patients were included. Relevant clinical and anthropometric data are summarized in Table 1. Patients with grades II or III IAH were more frequently male, had longer dialysis vintage, received more frequently hemodialysis as renal replacement therapy and suffered delayed graft function, graft loss or death more repeatedly. In Kaplan-Meier analysis, grade II IAH or higher were associated with lower composite-outcome free survival (Log-Rank: 8.053; p = 0.018) (Figure 1). Conclusion Grade II-III IAH appear to be a risk factor for graft loss or recipient death in our sample of deceased donor kidney transplant recipients. Monitoring of intra-abdominal hypertension could provide useful information to identify patients at higher risk of post-transplant complications.

#3973 EXCELLENT EFFICACY AND BENEFICIAL SAFETY DURING FIVE YEAR FOLLOW-UP OF RAPID STEROID WITHDRAWAL AFTER RENAL TRANSPLANTATION (HARMONY STUDY)

Abstract Background and Aims We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal in the randomized controlled one year “Harmony” trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. The five-year post-trial follow-up (FU) data reported here were obtained in an observational manner to evaluate, how these excellent short-term surrogate parameters will translate into hard long-term outcome parameters like patient death/graft loss. Method The five-year post-trial follow-up data were obtained in an observational manner at a three and a five-year visit for patients who consented to participate and covered clinical events that occurred from the second year onwards. Results Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of rapid steroid withdrawal (see Figure 1). Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95 % confidence interval 0.314 to 0.976; p = 0.041, see Table 1). The reduced incidence of post-transplantation diabetes mellitus in rapid steroid withdrawal patients during the original one-year study period was not compensated by later incidences during follow-up. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor specific antibody formation, or kidney function did not differ during follow-up period. Conclusion The Harmony follow-up trial confirms excellent efficacy and beneficial safety aspects of rapid steroid withdrawal under modern immunosuppressive therapy demonstrating for the first time increased patient survival in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients.

Predicting Long-term Outcomes in Deceased Donor Kidney Transplant Recipients Using Three Short-term Graft Characteristics.

Delayed graft function (DGF) in kidney transplant recipients is used to determine graft prognosis, make organ utilization decisions, and as an important end-point in clinical trials. However, DGF is not an ideal measure of graft function. We aimed to develop and validate a model that provides incremental risk assessment for inferior patient and graft outcomes. We included adult kidney-only deceased donor transplant recipients from 1996 to 2016. In addition to DGF, two short-term measures were used to assess risk: renal function recovery<100% (attaining half the donor's eGFR) and recipient's 90-day eGFR<30. Recipients were at no-, low-, moderate- or high-risk if they met zero, one, two, or all criteria, respectively. Cox proportional hazards models were used to assess the independent relationship between the exposure and death-censored graft failure (DCGF) and mortality. Of the 792 eligible recipients, 24.5% experienced DGF, 40.5% had renal function recovery<100% and 6.9% had eGFR<30. Over a median follow-up of 7.3 years, the rate of DCGF was 18.7% and mortality was 25.1%. When compared with recipients at no risk, those at low-, moderate- and high-risk were noted to have an incremental increase in risk of DCGF (aHR=1.53, 95%CI:1.03-2.27; aHR=2.84, 95%CI:1.68-4.79; aHR=15.46, 95%CI:8.04-29.71) and mortality (aHR=1.16, 95%CI:0.84-1.58; aHR=1.85, 95%CI:1.13-3.07; aHR=2.66 (95%CI:1.19-5.97). When using a hierarchical approach, each additional exposure predicted the risk of DCGF better than DGF alone and 100 random bootstrap replications supported the internal validity of the risk model. In an external validation cohort deemed to be at lower risk for DCGF, similar non-significant trends were noted. We propose a risk model that provides an incremental assessment of recipients at higher risk of adverse long-term outcomes than DGF alone. This can help advance the field of risk assessment in transplantation and inform therapeutic decision-making in patients at the highest spectrum of inferior outcomes.

The Association Between Kidney Donor Profile Index and 1-y Graft Function.

This single-center, retrospective cohort study analyzed data from 3059 consecutive deceased donor kidney transplant recipients with a 1-y follow-up from January 2013 to December 2017. The aim was to determine the association between the KDPI strata (0%-35%, 36%-50%, 51%-85%, 86%-100%) and 1-y eGFR estimated by the CKD-EPI equation. The incidence of delayed graft function (50.6% versus 59.3% versus 62.7% versus 62.0%; P < 0.001) and cytomegalovirus infection (36.7% versus 36.6% versus 43.3% versus 57.8%; P < 0.001) increased with increasing KDPI strata but not biopsy-proven acute rejection (9.1% versus 9.8% versus 8.4% versus 9.1%; P = 0.736). The median 1-y eGFR decreased with increasing KDPI strata (64.8 versus 53.5 versus 46.9 versus 39.1 mL/min/1.73 m2; P < 0.001). In the Cox regression, the higher the KDPI was, the lower the probability of a lower 1-y eGFR was. Assuming the 0%-35% strata as the reference, the likelihood of eGFR <50 mL/min/1.73 m2 was increased by 76.6% (hazard ratio [HR] = 1.767, 95% confidence interval [CI] = 1.406-2.220), 2.24- and 2.87-fold higher for KDPI higher >35%-50% (HR = 2.239, 95% CI = 1.862-2.691), and >51%-85% (HR = 2.871, 95% CI = 2.361-3.491), respectively. Other variables associated with a lower graft function were donor sex (HR male versus female = 0.896, 95% CI = 0.813-0.989) and cold ischemia time (HR for each hour = 1.011, 95% CI = 1.004-1.019). This association was sustained after the Poisson mediation analysis, including delayed graft function, cytomegalovirus, and acute rejection as mediators. In this cohort of deceased donor kidney recipients, KDPI, and cold ischemia time were the major independent risk factors associated with lower 1-y kidney function.