All-cause Graft Failure Research Articles

Thirty-Year Trends in Graft Survival After Heart Transplant: Modeled Analyses of a Transplant Registry

BackgroundHeart failure is an epidemic in the United States, and transplantation remains the most definitive therapy. We describe multidecade trends in posttransplant graft survival, adjusted for concurrent changes in the population, over the 30 years antecedent to the most recent heart allocation policy change. MethodsScientific Registry of Transplant Recipients data were used to identify all primary adult heart recipients from 1989 to 2017. We described temporal changes in population characteristics (recipient and donor demographics and comorbidities, pretransplant interventions, clinical transplant measures, and providers). The primary outcome was graft survival, defined as freedom from all-cause death and graft failure, within 6 months posttransplant. Modified Poisson logistic regression estimated relative changes in risk of outcomes compared with 1989, with and without adjustment for changing population characteristics. We identified risk factors, quantified by associated risk ratios. ResultsAmong 56,488 primary adult heart recipients, we observed 5529 (9.8%) all-cause deaths and 1933 (3.4%) graft failure events within 6 months posttransplant. Prevalence of known recipient risk factors increased over time. Unadjusted modeling demonstrated a significant 30-year improvement in graft survival, averaging 2.6% per year (95% confidence interval, 2.4-2.9; P for trend < .001). After adjusting for population changes the 30-year trend remained significant and graft survival improved on average 3.0% per year (95% confidence interval, 2.6-3.3). Regression modeling identified multiple predictors of graft survival. Modeling 2 additional outcomes of 6-month mortality and 6-month graft failure produced similar results. ConclusionsShort-term graft survival after heart transplantation has improved significantly leading up to the 2018 heart allocation policy change, despite concurrent increase in prevalence of higher risk population characteristics.

The Prognostic Role of Right Ventricular Stroke Work Index during Liver Transplantation.

Right heart-associated hemodynamic parameters including intraoperative pulmonary vascular resistance (PVR) were reported to be associated with patient survival after liver transplantation. We investigated whether intraoperative stroke work indexes of both ventricles could have a better prognostic value than PVR. We reviewed 683 cases at a tertiary care academic medical center. We collected intraoperative variables of baseline central venous pressure, baseline right ventricle end-diastolic volume, mixed venous oxygen saturation, intraoperative PVR and right and left ventricular stroke work indexes. Time-weighted means or area under the curve of intraoperative right and left ventricular stroke work indexes were calculated as exposure variables. One-year all-cause mortality or graft failure was our primary outcome. Cox proportional hazard regression analysis was performed to evaluate the association between exposure variables and one-year all-cause mortality or graft failure. Kaplan–Meier survival curve analysis of our primary outcome was performed for different time-weighted mean ventricular stroke work index groups. Cubic spline curve analysis was performed to evaluate the linear relationship between our exposure variables and primary outcome. Time-weighted mean right ventricular stroke work index was significantly associated with one-year all-cause mortality or graft failure (hazard ratio 1.21, 95% confidence interval (CI) 1.12–1.36, p < 0.001). However, there was no significant association between time-weighted mean left ventricular stroke work index, time-weighted mean PVR, PVR at the end of surgery and one-year mortality. Area under the curve of right ventricular stroke work index was also significantly associated with one-year mortality or graft failure (hazard ratio 1.24, 95% CI 1.15–1.37, p < 0.001). Kaplan–Meier survival curve analysis showed a significant difference in the survival between different mean right ventricular stroke work index groups (Log-rank test: p = 0.002). Cubic spline function curve showed the gradual increase in the risk of mortality with a positive slope with time-weighted mean right ventricular stroke work index. In conclusion, intraoperative elevated right ventricular stroke work index was significantly associated with poor patient or graft survival after liver transplantation. Intraoperative right ventricular stroke work index could be an intraoperative hemodynamic goal and prognostic marker for mortality after liver transplantation.

Post-transplantation erythrocytosis in kidney transplant recipients-A retrospective cohort study.

To characterize risk factors for the development of post-transplant erythrocytosis (PTE), and its long-term effect on mortality, graft failure, and thrombosis. Retrospective study including all kidney transplant recipients in Rabin Medical Center (RMC) during the years 2005-2014. The primary outcome was a composite outcome of all-cause mortality or graft failure at the end of follow-up. Secondary outcomes included death censored graft loss, venous thromboembolism, major adverse cardiovascular events, and mortality. A matched control group was also evaluated. Univariate and multivariate time-varying Cox model analyses were conducted for outcome evaluation. A total of 1304 patients were included, 169 of whom were diagnosed with PTE (12.9%). PTE was associated with male gender, higher glomerular filtration rate (GFR), and polycystic kidney disease. PTE was found to be associated with a reduced risk of the primary outcome (HR 0.355, CI 95% 0.151-0.89, P=.027) in a univariate time-varying Cox analysis, but was not associated with the composite outcome in a multivariate analysis. There was no difference in the primary outcome when the PTE group was compared with the matched control. PTE was not found to be associated with long-term outcomes of graft failure and poor survival.

Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study.

De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P<0.001) and higher BMI (P=0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM. PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time.

Clinical Correlates and Outcomes of Dual Basiliximab and Antithymocyte Globulin Induction in Kidney Transplant Recipients: A National Study.

We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 y, according to induction therapy type, was assessed using multivariate Cox regression analysis (adjusted hazard ratio with 95% upper and lower confidence limits [LCLaHRUCL]). Of the 157 351 recipients included in the study, 67% were treated with ATG alone, 29% were treated with IL2rAb alone, and 5% were treated with both. Compared with IL2rAb alone, the strongest correlates of dual induction included Black race, calculated panel reactive antibody ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with ATG alone, dual induction was associated with an increased 5-y risk of death (aHR 1.071.151.23; P < 0.0001), death-censored graft failure (aHR 1.051.131.22; P < 0.05), and all-cause graft failure (aHR 1.061.121.18; P < 0.0001). Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.

Donor-Recipient BSA Matching Is Prognostically Significant in Solitary and En Bloc Kidney Transplantation From Pediatric Circulatory Death Donors.

Background.As the rate of early postoperative complications decline after transplant with pediatric donation after circulatory death (DCD) kidneys, attention has shifted to the long-term consequences of donor–recipient (D-R) size disparity given the pernicious systemic effects of inadequate functional nephron mass.Methods.We conducted a retrospective cohort study using Organ Procurement and Transplantation Network data for all adult (aged ≥18 y) recipients of pediatric (aged 0–17 y) DCD kidneys in the United States from January 1, 2004 to March 10, 2020.Results.DCD pediatric allografts transplanted between D-R pairs with a body surface area (BSA) ratio of 0.10–0.70 carried an increased risk of all-cause graft failure (relative risk [RR], 1.36; 95% confidence interval [CI], 1.10–1.69) and patient death (RR, 1.32; 95% CI, 1.01–1.73) when compared with pairings with a ratio of >0.91. Conversely, similar graft and patient survivals were demonstrated among the >0.70–0.91 and >0.91 cohorts. Furthermore, we found no difference in death-censored graft survival between all groups. Survival analysis revealed improved 10-y patient survival in recipients of en bloc allografts (P = 0.02) compared with recipients of single kidneys with D-R BSA ratios of 0.10–0.70. A similar survival advantage was demonstrated in recipients of solitary allografts with D-R BSA ratios >0.70 compared with the 0.10–0.70 cohort (P = 0.02).Conclusions.Inferior patient survival is likely associated with systemic sequelae of insufficient renal functional capacity in size-disparate DCD kidney recipients, which can be overcome by appropriate BSA matching or en bloc transplantation. We therefore suggest that in DCD kidney transplantation, D-R BSA ratios of 0.10–0.70 serve as criteria for en bloc allocation or alternative recipient selection to optimize the D-R BSA ratio to >0.70.

Kidney Transplant Outcomes in Indigenous People of the Northern Great Plains of the United States

Indigenous people experience higher rates of end-stage renal disease as well as negative predictive factors that undermine kidney transplantation (KT) success. Despite these inequalities, data suggest that short-term outcomes are comparable to those of other groups, but few studies have examined this effect in the Northern Great Plains (NGP) region. We performed a retrospective database review to determine outcomes of KT in Indigenous people of the NGP. White and Indigenous people receiving a KT between 2000 and 2018 at a single center were examined. A total of 622 KT recipients were included (117 Indigenous and 505 White). Indigenous patients were more likely to smoke, have diabetes, have higher immunologic risk, receive fewer living donor kidneys, and have longer waitlist times. In the 5 years after KT there were no significant differences in renal function, rejection events, cancer, graft failure, or patient survival. At 10 years posttransplant, Indigenous patients had twice the all-cause graft failure (odds ratio=2.06; 95% confidence interval, 1.25-3.39) and half the survival rate (odds ratio=0.47; 95% confidence interval, 0.29-0.76); however, this effect was not maintained once the effects of race, sex, smoking status, diabetes, preemptive transplant, high panel reactive antibody status, and transplant type were adjusted for. KT outcomes in Indigenous patients in the NGP region are similar to those of White patients 5 years posttransplant, with differences emerging at 10 years that could be diminished with greater emphasis on correcting modifiable risk factors.

Analyzing Association Rules for Graft Failure Following Deceased and Live Donor Kidney Transplantation.

This paper investigates the clinical attributes that contribute to kidney graft failure following live and deceased donor transplantation using an association rule mining approach. The generated rules are used to analyze the distinctive co-occurrence of attributes for those with or without all-cause graft failure. Analysis of a kidney transplantation dataset acquired from the Scientific Registry of Transplant Recipients that included over 95000 deceased and live donor recipients over 5-years was performed. Using an association rule mining approach, we were able to confirm established risk factors for graft loss after live and deceased donor transplantation and identify novel combinations of factors that may have implications for clinical care and risk prediction post kidney transplantation. Using lift as the metric to evaluate association rules, our results indicate that advanced recipient age (i.e. over 60 years), end stage kidney disease due to diabetes, the presence of recipient peripheral vascular disease and recipient coronary artery disease have a high likelihood of graft failure within 5 years after transplantation.

POS-744 CLINICAL CORRELATES AND OUTCOMES OF DUAL BASILIXIMAB AND THYMOGLOBULIN INDUCTION IN KIDNEY TRANSPLANT RECIPIENTS: A NATIONAL STUDY

The unplanned use of dual induction therapy with interleukin-2 receptor blocking antibodies (IL2rAb) and thymoglobulin (TMG) may portend adverse clinical outcomes compared to either therapy alone. We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 years according to induction therapy type was assessed using multivariate Cox regression analysis (LCLaHRUCL, adjusted hazard ratio with 95% upper and lower confidence limits). Of the 157,351 adult kidney-only transplant recipients included in the study, 67% were treated with TMG alone, 29% were treated with IL2rAb alone, and 5% were treated with both IL2rAb and TMG. Compared with IL2rAb alone induction, the strongest correlates of IL2rAb and TMG induction included Black race, calculated panel reactive antibody (cPRA) ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with induction with TMG alone, dual induction therapy was associated with an increased 5-year risk of death (aHR 1.071.151.23; P<0.0001), death-censored graft failure (aHR 1.051.131.22; P<0.05), and all-cause graft failure (aHR 1.061.121.18; P<0.0001). Approximately 15% of kidney transplant patients who received IL2rAb induction also received TMG induction and these recipients had an increased risk of death and graft loss compared with those who received TMG alone. Further research is needed to develop risk prediction tools to guide a safe and optimal induction protocol for kidney transplant recipients.

Impact of deceased donor with acute kidney injury on subsequent kidney transplant outcomes-an ANZDATA registry analysis.

BackgroundThe need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature.Material and methodsThis observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection.ResultsThe study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99–1.26), death-censored graft failure (HR 1.09, 95% CI 0.92–1.28), death (HR 1.15, 95% CI 0.98–1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91–1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92–2.68).ConclusionDonor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

Relative decrease in hemoglobin and outcomes in patients undergoing kidney transplantation surgery: A retrospective cohort study

BackgroundRecent surgical literature suggests that a relative decrease in hemoglobin (ΔHb) is predictive of adverse outcomes regardless of the absolute level. We aimed to examine the association between perioperative ΔHb and kidney transplantation (KT) outcomes. MethodsThis was a retrospective cohort study of transplant recipients, where ΔHb = [Hb0– Hb1Hb0]x 100 (Hb0 = hemoglobin pre-KT and Hb1 = lowest hemoglobin 24-h post-KT). The main outcome of interest was immediate graft function (IGF). ResultsOf the 899 eligible patients, 38% experienced IGF, and ΔHb was associated with 36% lower odds of IGF. Also, ΔHb was associated with higher all-cause graft failure and longer length of stay but not death-censored graft failure or mortality. ΔHb ≥30% was the threshold beyond which the odds of IGF were significantly lower even if Hb1 was ≥7 g/dL. ConclusionΔHb is associated with inferior outcomes independent of Hb1; whether it can be used to guide transfusion practices should be explored.

Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation.

There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx). We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up. A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of -0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of -9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years. If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR.

Right Ventricular Dysfunction and Adverse Outcomes after Renal Transplantation

Introduction: Pulmonary hypertension is common among patients with end-stage renal disease, although data regarding the impact of right ventricular (RV) failure on postoperative outcomes remain limited. We hypothesized that echocardiographic findings of RV dilation and dysfunction are associated with adverse clinical outcomes after renal transplant. Methods: A retrospective review of adult renal transplant recipients at a single institution from January 2008 to June 2010 was conducted. Patients with transthoracic echocardiograms (TTEs) within 1 year leading up to transplant were included. The primary end point was a composite of delayed graft function, graft failure, and all-cause mortality. Results: Eighty patients were included. Mean follow-up time was 9.4 ± 0.8 years. Eight patients (100%) with qualitative RV dysfunction met the primary end point, while 39/65 patients (60.0%) without RV dysfunction met the end point (p = 0.026). Qualitative RV dilation was associated with a significantly shorter time to all-cause graft failure (p = 0.03) and death (p = 0.048). RV systolic pressure was not measurable in 45/80 patients (56%) and was not associated with outcomes in the remaining patients. Conclusion: RV dilation and dysfunction are associated with adverse outcomes after renal transplant. TTE assessment of RV size and function should be a standard part of the pre-kidney transplant cardiovascular risk assessment.

Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

Acute Kidney Injury in Deceased Organ Donors and Kidney Transplant Outcomes: A National Cohort Study Using a Novel Data Source.

The aim of this study was to determine graft function and survival for kidney transplants from deceased donors with acute kidney injury (AKI) that persists at the time of organ procurement. Kidneys from donors with AKI are often discarded and may provide an opportunity to selectively expand the donor pool. Using Organ Procurement and Transplantation Network and DonorNet data, we studied adult kidney-only recipients between May 1, 2007 and December 31, 2016. DonorNet was used to characterize longitudinal creatinine trends and urine output. Donor AKI was defined using KDIGO guidelines and terminal creatinine ≥1.5 mg/dL. We compared outcomes between AKI kidneys versus "ideal comparator" kidneys from donors with no or resolved AKI stage 1 plus terminal creatinine <1.5mg/dL. We fit proportional hazards models and hierarchical linear regression models for the primary outcomes of all-cause graft failure (ACGF) and 12-month estimated glomerular filtration rate (eGFR), respectively. We identified 7660 donors with persistent AKI (33.2% with AKI stage 3) from whom ≥1 kidney was transplanted. Observed rates of ACGF within 3 years were similar between recipient groups (15.5% in AKI vs 15.1% ideal comparator allografts, P = 0.2). After risk adjustment, ACGF was slightly higher among recipients of AKI kidneys (adjusted hazard ratio 1.05, 95% confidence interval: 1.01-1.09). The mean 12-month eGFR for AKI kidney recipients was lower, but differences were not clinically important (56.6 vs 57.5 mL/min/1.73m 2 for ideal comparator kidneys; P < 0.001). There were 2888 kidneys discarded from donors with AKI, age ≤65 years, without hypertension or diabetes, and terminal creatinine ≤4 mg/dL. Kidney allografts from donors with persistent AKI are often discarded, yet those that were transplanted did not have clinically meaningful differences in graft survival and function.

S1005 The Implications of Chronic Opioid Use on Post-Transplant Clinical Outcomes: A Systematic Review and Meta-Analysis

INTRODUCTION: Based on current literature, pre-transplant chronic opioid use (COU) for analgesia is highly prevalent among patients awaiting solid-organ transplant. However, there are very few large-scale studies on the effect of COU on post-transplant outcomes. We conducted a systematic review and meta-analysis to evaluate the impact of pre-transplant COU on solid-organ transplantation clinical outcomes. METHODS: A comprehensive literature review was conducted by searching the PubMed, Ovid Medline, Embase, Web of Science, and Cochrane databases from inception to April 2020 to identify all studies that evaluated the impact of pre-transplant COU on post-transplant clinical outcomes. COU was defined as >3 months of consecutive opioid use entering transplant listing. The search included studies regarding heart, lung, kidney, and liver transplantation (Figure 1). Our primary outcome was all-cause mortality, and secondary outcomes were graft failure and the one-year readmission rate. A random-effect model was used to estimate the pooled hazard ratios (HR) or odds ratios (OR) of our outcomes. RESULTS: Nine retrospective studies involving 166,765 patients were included in the primary meta-analysis. The all-cause mortality rate was significantly higher in patients who were on chronic opioids preceding transplant compared to those who were not (HR 1.42; 95% CI 1.34-1.50). The included studies demonstrated low heterogeneity (Figure 2). Additionally, COU patients had an increased risk of graft failure compared to non-COU patients (HR 1.26; 95% CI (1.13–1.40) (Figure 3). With regards to the one-year readmission rates, only three studies were included. There was no statistically significant difference in the readmission rate between the two groups (HR 1.78; 95% CI (0.87–3.63). The three studies had high heterogeneity. CONCLUSION: This study demonstrates that pre-transplant COU in solid-organ transplant patients is associated with an increased risk of all-cause mortality and graft failure. Pre-transplant COU may be a surrogate for comorbidities causing chronic pain or psychosocial traits that can contribute to non-compliance post-transplant. These potential risk factors may explain the increased risk of poor outcomes post-transplant. Therefore, a careful evaluation of opioid use patterns and consideration of alternative analgesic strategies is warranted in this population to lessen the reliance on opioid use and associated adverse outcomes.Figure 1.: Literature review process.Figure 2.: Forest plot of mortality.Figure 3.: Forest plot of graft loss.

ABDOMINAL AORTA CALCIFICATION PRIOR TO KIDNEY TRANSPLANTATION: THE ASSOCIATION WITH PATIENT AND GRAFT SURVIVAL

Dutch Kidney Transplant Study Group. Introduction: A high degree of vascular calcification is commonly encountered in patients undergoing kidney transplantation, especially in those who were on long-term hemodialysis. The prognostic value of pre-transplant vascular calcification for patient and graft survival is unclear. Therefore, this study focused on the association of abdominal aortic calcification (AAC) prior to kidney transplantation and both all-cause mortality and graft failure. Materials and Methods: From 2005 to 2018, renal transplant recipients referred for a nonenhanced CT procedure within 3 years prior to kidney transplantation, were included in a dual-centre study. Primary endpoints were all-cause mortality and graft failure after kidney transplantation. AAC was retrospectively quantified using a semiautomated tool, as a modified Agatston score. Patients were stratified into three groups based on the AAC quantification results. A Kaplan-Meier curve, with Log Rank analysis, and a Cox proportional hazards model were used for time-to-event analysis. Multivariate analysis included the AAC score in quartiles, recipient age, sex and Body Mass Index (BMI) at moment of transplantation, duration of dialysis prior to transplantation and history of smoking. Results: We evaluated 547 patients, 461 (84.3%) had detectable calcifications and the median time between CT and transplantation was 1.0 (IQR 0.5 – 1.4) years. Sixty-nine (12.6%) patients died and 84 (15.4%) had graft failure during a median follow-up of 2.5 (IQR 1.0 – 4.3) years. Kaplan-Meier curves indicate that a higher AAC score was associated with a higher all-cause mortality (p < 0.001) (Figure 1.) and higher rate of graft failure (p = 0.009) (Figure 2.). Similarly, in univariate Cox proportional hazard analysis a high AAC score was associated with a higher all-cause mortality (HR 4.3 (95% CI 2.2 – 8.4, p < 0.001) and a higher rate of graft failure (HR 2.1 (95% CI 1.3 – 3.6, p < 0.004). These associations remained significant upon multivariate analysis, with HR 3.1 (95% CI 1.3 – 7.0), p = 0.008) and (HR 2.0 (95% CI 1.2 – 3.5, p < 0.00) for mortality and graft failure, respectively. Fig. 1.Fig. 2.Conclusion: A significant association between the degree of AAC, assessed by nonenhanced CT-based quantification, and both all-cause mortality and graft failure was identified. A validated scoring system for AAC could guide clinicians in decision-making with regard to risk stratification and expected patient-related outcomes after kidney transplantation.

CARDIOVASCULAR DISEASE AFTER KIDNEY TRANSPLANTATION: A NATIONWIDE STUDY IN SOUTH KOREA

Background: Cardiovascular disease (CVD) is the most common cause of death in end-stage renal disease (ESRD). Kidney transplantation (KT) is an effective treatment for ESRD, and is known as lowering risk for CVD compared to the ESRD patients on the transplantation waiting list. However, there is a lack of large-population studies especially for Asians. Method: We analyzed the nationwide health insurance database of South Korea and identified patients who received kidney transplantation from the year of 2007 to 2015. Patients who were under 20 years of age, had previous CVD identified, or had multiorgan transplantation were excluded from the study. As controls, ESRD and GP groups were extracted after same exclusion and matching with KT recipients by age, sex, and inclusion year. CVD was defined as major cardiovascular events (MACEs) consisted of myocardial infarction, ischemic stroke, and all-cause mortality. Result: During the study period, a total of 13,179 patients received KT. After exclusion, 4,156 KT recipients were selected. The same number of ESRD and GP control were extracted after matching. Mean age was 41.3 ± 10.2 years and 55.2% were men in all 3 groups. KT recipients had similar proportions of diabetes and hypertension and a lower proportion of dyslipidemia compared with ESRD controls, although significantly higher co-morbidities than GP controls. The total number of MACEs was 76 (3.7 per 1000 person-year) in KT recipients, 377 (21.7 per 1000 person-year) in ESRD, 51 (2.5 per 1000 person-year) in GP, respectively. KT recipients showed a significantly lower MACE risk (adjusted HR 0.16, 95% CI 0.12-0.20, p <0.001) than ESRD controls. And the MACE risks were not significantly different between KT recipients and matched GP controls (adjusted HR 0.81, 95% CI 0.52-1.27, p=0.365). When subgroup analysis of age, sex, diabetes and hypertension was performed, similar trends were observed regardless of subgroups. Meanwhile, KT recipients who occurred MACE showed significant elevated risk of all-cause mortality and graft failure (HR 7.45, 95% CI 4.21-13.21, p<0.001 and HR 2.49, 95% CI 1.52-4.09, p<0.001, respectively). Conclusion: In this study, we found that the KT recipients had a lower risk of newly onset MACE after transplantation compared to patients maintaining dialysis in Korea, and showed a similar MACE risk compared to the general population.

Machine learning to predict transplant outcomes: helpful or hype? A national cohort study.

An increasing number of studies claim machine learning (ML) predicts transplant outcomes more accurately. However, these claims were possibly confounded by other factors, namely, supplying new variables to ML models. To better understand the prospects of ML in transplantation, we compared ML to conventional regression in a "common" analytic task: predicting kidney transplant outcomes using national registry data. We studied 133431 adult deceased-donor kidney transplant recipients between 2005 and 2017. Transplant centers were randomly divided into 70% training set (190 centers/97787 recipients) and 30% validation set (82 centers/35644 recipients). Using the training set, we performed regression and ML procedures [gradient boosting (GB) and random forests (RF)] to predict delayed graft function, one-year acute rejection, death-censored graft failure C, all-cause graft failure, and death. Their performances were compared on the validation set using -statistics. In predicting rejection, regression (C=0.601 0.6110.621 ) actually outperformed GB (C=0.581 0.5910.601 ) and RF (C=0.569 0.5790.589 ). For all other outcomes, the C-statistics were nearly identical across methods (delayed graft function, 0.717-0.723; death-censored graft failure, 0.637-0.642; all-cause graft failure, 0.633-0.635; and death, 0.705-0.708). Given its shortcomings in model interpretability and hypothesis testing, ML is advantageous only when it clearly outperforms conventional regression; in the case of transplant outcomes prediction, ML seems more hype than helpful.

Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.

Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.