Risk Of Death-censored Graft Failure Research Articles

Pretransplant and Posttransplant Alcohol Consumption and Outcomes in Kidney Transplantation: A Prospective Multicenter Cohort Study.

The impact of pretransplant and posttransplant alcohol consumption on outcomes in kidney transplant recipients (KTRs) is uncertain. Self-reported alcohol consumption was obtained at the time of transplant and 2 years after transplant in a prospective cohort study. Among 907 KTRs, 368 (40.6%) were drinkers at the time of transplant. Compared to non-drinkers, alcohol consumption did not affect the risk of death-censored graft failure (DCGF), biopsy-proven acute rejection (BPAR), cardiovascular events, or all-cause mortality. Compared to persistent non-drinkers, the development of DCGF, BPAR, cardiovascular events, all-cause mortality, or posttransplant diabetes mellitus was not affected by the alcohol consumption pattern (persistent, de novo, or stopped drinking) over time. However, de novo drinkers had a significantly higher total cholesterol (p < 0.001) and low-density lipoprotein cholesterol levels (p = 0.005) compared to persistent non-drinkers 5 years after transplant, and had significantly higher total cholesterol levels (p = 0.002) compared to the stopped drinking group 7 years after transplant, even after adjusting for the use of lipid-lowering agents, age, sex, and body mass index. Although pretransplant and posttransplant alcohol consumption were not associated with major outcomes in KTRs during the median follow-up of 6.0 years, a new start of alcohol use after KT results in a relatively poor lipid profile. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02042963.

Clinical Significances of Anti-Collagen Type I and Type III Antibodies in Antibody-Mediated Rejection.

It is important to determine the clinical significance of non-human leukocyte antigen (HLA) antibodies and their association with antibody-mediated rejection (ABMR) of kidney allografts. We collected post-transplant sera from 68 ABMR patients, 67 T-cell mediated rejection (TCMR) patients, and 83 control subjects without rejection, and determined the titers of 39 non-HLA antibodies including antibodies for angiotensin II receptor type I and MICA. We compared all these non-HLA antibody titers among the study groups. Then, we investigated their association with the risk of death-censored graft failure in ABMR cases. Among the antibodies evaluated, anti-collagen type I (p = 0.001) and type III (p < 0.001) antibody titers were significantly higher in ABMR cases than in both TCMR cases and no-rejection controls. Both anti-collagen type I [per 1 standard deviation (SD), adjusted odds ratio (OR), 11.72 (2.73-76.30)] and type III [per 1 SD, adjusted OR, 6.22 (1.91-31.75)] antibodies were significantly associated with the presence of ABMR. Among ABMR cases, a higher level of anti-collagen type I [per 1 SD, adjusted hazard ratio (HR), 1.90 (1.32-2.75)] or type III per 1 SD, [adjusted HR, 1.57 (1.15-2.16)] antibody was associated with a higher risk of death-censored graft failure. In conclusion, post-transplant anti-collagen type I and type III antibodies may be novel non-HLA antibodies related to ABMR of kidney allografts.

Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes

Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster's key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Machine learning consensus clustering approach. Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups.

The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure.

Donor-specific antibodies (DSA) against HLA are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid-organ transplant recipients. However, the impact of DSA with or without histopathological evidence of rejection among pancreas transplant recipients (PTRs) is unknown. In this study, we included all PTRs at our center between 2005 and 2020, with pancreas allograft biopsy before March 31, 2021, and with DSA checked within 15 d of the biopsy. PTRs were divided into 4 groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-, Rej+/DSA-, Rej-/DSA+, and Rej+/DSA+. Two hundred two PTRs had a pancreas allograft biopsy during the study period. Thirty-nine were in Rej-/DSA-, 84 Rej+/DSA-, 24 Rej-/DSA+, and 55 Rej+/DSA+. The mean interval from transplant to index biopsy was not statistically different between the 4 groups. The most common type of rejection was T cell-mediated rejection; however, antibody-mediated rejection was more prevalent in the Rej+/DSA+ group. At 5 y postbiopsy, the rate of death-censored graft failure (DCGF) for Rej-/DSA- was 18%, 24% in Rej+/DSA-; 17% in Rej-/DSA+ and 36% in Rej+/DSA+ (P = 0.14). In univariate analysis, mixed rejection (hazard ratio [HR], 3.0; 95% confidence intervals [CI], 1.22-7.39; P = 0.02) along with solitary pancreas transplantation and Rej+/DSA+ were associated with DCGF. In multivariate analysis, compared with Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR, 2.32; 95% CI, 1.03-5.20; P = 0.04); however, Rej+/DSA- was not (HR, 1.06; 95% CI, 0.32-3.56; P = 0.92). PTRs with pancreas allograft rejection and concomitant DSA have an increased risk of DCGF.

Not all eplet mismatches are created equal – A cohort study illustrating implications to long-term graft outcomes

We assessed implications of various eplet-compatibility strategies to death-censored graft failure (DCGF), defined as return to dialysis or re-transplantation, in a base-case scenario from the Scientific Registry of Transplant Recipients. To inform personalized care, we evaluated how recipient, donor, and transplant characteristics affect DCGF by ascending categories of eplet mismatches (EMM), and derived adjusted hazard ratios (HR). The base-case analysis demonstrated 15-year estimated survival probabilities of 77.1%, 75.4%, 73.6%, 72.2%, 74.9%, and 73.5% for the lowest EMM categories (complete epitype: 0–19, antibody-verified (AbVer) epitype and class II eplets: 0–9, class II AbVer eplets: 0–4, 55 high-risk eplets associated with DCGF: 0–3, and subset of 15 high-risk eplets validated in an independent subcohort: 0 EMM, respectively). Beyond the lowest EMM categories, the Epi15 strategy allowed better differentiation of change in DCGF risk per EMM, with additional 5.2%, 3.9% and 4.1% decrease in estimated graft survival for each additional EMM (1, 2, and ≥ 3, respectively). Recipients < 25 years, donors > 55 years, and immunosuppression regimens excluding calcineurin inhibitors and steroids, demonstrated higher HR for DCGF. High-risk EMM allowed better differentiation between DCGF probabilities per EMM, suggesting that recipients at higher risk for graft failure could benefit most from allocation schemes ensuring compatibility on these eplets.

208.1: The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure

Introduction: Donor-specific antibodies (DSA) against human leukocyte antigen (HLA) are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid organ transplant recipients. However, the impact of DSA with or without Rej among pancreas transplant recipients (PTRs) is unknown. Method: In this study, we included all PTRs who had undergone either simultaneous pancreas-kidney or solitary pancreas transplant at our center between 2005 and 2020, with pancreas allograft biopsy before 03/2021, and with DSA checked within 15 days of the biopsy. Among PTRs with multiple biopsies during the study period, the first index biopsy was used to analyze the data. Pancreas biopsies at the time of implant or explant were excluded, as were biopsies with no pancreas tissue present. PTRs were divided into four groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-; Rej+/DSA-; Rej-/DSA+ and Rej+/DSA+. Results: A total of 352 pancreas allograft biopsies were performed in 203 PTRs during the study period. Of these, 203 PTRs, 41 were in Rej-/DSA-; 87 Rej+/DSA-; 24 Rej-/DSA+; and 51 Rej+/DSA+. Most of the baseline characteristics were similar between the groups, except PTRs in Rej-/DSA+ and Rej+/DSA+ were relatively younger, with a mean age of 39 compared to 43 for the other two groups. The mean interval from transplant to index biopsy was not statistically different between the four groups. The most common rejection was TCMR, however, AMR was more prevalent in the Rej+/DSA+ group. In addition, DSA against class II HLA was more prevalent in the DSA+/Rej + group. There was no statistical difference in the mean post index biopsy follow-up. At last follow up, the rate of death censored graft failure (DCGF) for Rej-/DSA- was 22%, 29% in Rej+/DSA-; 17% in Rej-/DSA+ and 39% in Rej+/DSA+. Although not statistically significant, there was a trend towards inferior pancreas graft survival in Rej+/DSA+ group by unadjusted K-M survival analysis (Figure 1).In multivariable analysis compared to Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR: 2.25, 95% CI: 1.02 to 4.97; p=0.04), however Rej+/DSA- was not (HR: 1.40; 95% CI: 0.65 to 3.0; p=0.39). Conclusions: PTRs with pancreas allograft rejection in the presence of DSA have an increased risk of DCGF, and may warrant particularly aggressive management.

Association of Ambient Fine Particulate Matter Air Pollution With Kidney Transplant Outcomes

Increased levels of ambient fine particulate matter (PM2.5) air pollution are associated with increased risks for detrimental health outcomes, but risks for patients with kidney transplants (KTs) remain unknown. To investigate the association of PM2.5 exposure with KT outcomes. This retrospective cohort study was conducted using data on patients who received KTs from 2004 to 2016 who were identified in the national US transplant registry and followed up through March 2021. Multiple databases were linked to obtain data on PM2.5 concentration, KT outcomes, and patient clinical, transplant, and contextual factors. Data were analyzed from April 2020 through July 2021. Exposures included post-KT time-dependent annual mean PM2.5 level (in 10 μg/m3) and mean PM2.5 level in the year before KT (ie, baseline levels) in quartiles, as well as baseline annual mean PM2.5 level (in 10 μg/m3). Acute kidney rejection (ie, rejection within 1 year after KT), time to death-censored graft failure, and time to all-cause death. Multivariable logistic regression for kidney rejection and Cox analyses with nonlinear assessment of exposure-response for death-censored graft failure and all-cause death were performed. The national burden of graft failure associated with PM2.5 levels greater than the Environmental Protection Agency recommended level of 12 μg/m3 was estimated. Among 112 098 patients with KTs, 70 522 individuals (62.9%) were older than age 50 years at the time of KT, 68 117 (60.8%) were men, and the median (IQR) follow-up was 6.0 (3.9-8.9) years. There were 37 265 Black patients (33.2%), 17 047 Hispanic patients (15.2%), 48 581 White patients [43.3%]), and 9205 patients (8.2%) of other race or ethnicity. The median (IQR) baseline PM2.5 level was 9.8 (8.3-11.9) μg/m3. Increased baseline PM2.5 level, compared with quartile 1 baseline PM2.5 level, was not associated with higher odds of acute kidney rejection for quartile 2 (adjusted odds ratio [aOR], 0.99; 95% CI, 0.92-1.06) but was associated with increased odds for quartile 3 (aOR, 1.11; 95% CI, 1.04-1.20) and quartile 4 (aOR, 1.13; 95% CI, 1.05-1.23). Nonlinear assessment of exposure-response for graft failure and death showed no evidence for nonlinearity. Increased PM2.5 levels were associated with increased risk of death-censored graft failure (adjusted hazard ratio [aHR] per 10 μg/m3 increase, 1.17; 95% CI, 1.09-1.25) and all-cause death (aHR per 10 μg/m3 increase, 1.21; 95% CI, 1.14-1.28). The national burden of death-censored graft failure associated with PM2.5 above 12 μg/m3 was 57 failures (95% uncertainty interval, 48-67 failures) per year among patients with KTs. This cohort study found that PM2.5 level was an independent risk factor associated with acute rejection, graft failure, and death among patients with KTs. These findings suggest that efforts toward decreasing levels of PM2.5 concentration may be associated with improved outcomes after KT.

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF<7days, 576 (31·2%) had DGF 7-14days, and 345 (18·7%) had DGF >14days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p=·001) and recipient death (hazard ratio 1·8, p<·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14days is a novel early biomarker for significantly worse longer-term outcomes.

Association between early post-transplant hypertension or related antihypertensive use and prognosis of kidney transplant recipients: a nationwide observational study.

Additional research is warranted for the clinical significance of post-transplant hypertension and related antihypertensive medication use in kidney transplant (KT) recipients. This observational study included nationwide KT recipients who maintained a functioning graft for at least 1year after KT in South Korea, observed between 2008 and 2017. The use of antihypertensive medications lasting between 6months and 1year was the main exposure, and those who had inconsistent/transient use of antihypertensive drugs were excluded. The prognostic outcome included death-censored graft failure (DCGF), death-with functioning graft (DWFG), and major adverse cerebrocardiovascular events (MACCEs). We included 8,014 patients without post-transplant hypertension and 6,114 recipients who received treatment for hypertension in the post-transplant period. Those with post-transplant hypertension had asignificantly higherrisk of DCGF than those without [adjusted hazard ratio (HR) 1.27 (1.09-1.48)]. Post-transplant hypertension patients who required multiple drugs showed asignificantly higher risk of DWFG [HR 1.57 (1.17-2.10)] and MACCE [HR 1.35 (1.01-1.81)] than the controls. Among the single-agent users, those who received beta-blockers showed a significantly higher risk of DCGF, although the risks of DWFG or MACCE were similar between the types of antihypertensive agents. Among the multiple agent users, the prognosis was similar, regardless of the prescribed types of antihypertensive agents. Post-transplant hypertension was associated with poor post-transplant prognosis, particularly when multiple types of medications were required for treatment. During initial prescription of antihypertensive medication, clinicians may consider that beta-blockers were associated with a higher risk of DCGF in the single-agent users.

Clinical outcomes associated with long-term exposure to airborne particulate pollution in kidney transplant recipients

BackgroundResearchers have yet to investigate the specific association between 10-μm particulate matter (PM10) levels and the risk of graft failure, kidney disease, or the functional decline of transplanted kidneys, in kidney transplant recipients (KTRs). Furthermore, we know very little about the association between PM10 levels and the development of allograft rejection in transplanted kidneys. Identification of air pollution as a potential contributor to kidney disease could help reduce future disease burden, stimulate policy discussions on the importance of reducing air pollution with respect to health and disease, and increase public awareness of the hazards of air pollution. We aimed to evaluate the relationship of PM10 with the risk of graft failure, mortality, and decline of graft function in KTRs.MethodsAir pollutant data were obtained from the Korean National Institute of Environmental Research. We then investigated potential associations between these data and the clinical outcomes of 1532 KTRs who underwent kidney transplantation in a tertiary hospital between 2001 and 2015. Survival models were used to evaluate the association between PM10 concentrations and the risk of death-censored graft failure (DCGF), all-cause mortality, and biopsy-proven rejection (BPR), over a median follow-up period of 6.31 years.ResultsThe annual mean PM10 exposure after kidney transplantation was 27.1 ± 8.0 μg/m3. Based on 1-year baseline exposure, 1 μg/m3 increase in PM10 concentration was associated with an increased risk of DCGF (hazard ratio (HR): 1.049; 95% confidence interval (CI): 1.014–1.084) and BPR (HR: 1.053; 95% CI: 1.042–1.063). Fully adjusted models showed that all-cause mortality was significantly associated with 1-year average PM10 concentrations (HR, 1.09; 95% CI, 1.043 to 1.140).ConclusionsLong-term PM10 exposure is significantly associated with BPR, DCGF, and all-cause mortality in KTRs.

Incidence, risk factors, treatment, and consequences of antibody-mediated kidney transplant rejection: A systematic review.

Antibody-mediated rejection (AMR) is a leading cause of kidney allograft failure, but its incidence, risk factors, and outcomes are not well understood. We searched Ovid MEDLINE, Cochrane, EMBASE, and Scopus from January 2000 to January 2020 to identify published cohorts of ≥500 incident adult or 75 pediatric kidney transplant recipients followed for ≥1year post-transplant. At least two reviewers screened 5061 articles and abstracts; 28 met inclusion criteria. Incidence of acute AMR was 1.1%-21.5%; most studies reported 3%-12% incidence, usually within the first year post-transplant. Few studies reported chronic AMR incidence, from 7.5%-20.1% up to 10 years. Almost all patients with acute or chronic AMR received corticosteroids and intravenous immunoglobulin; most received plasmapheresis, and approximately half with rituximab. Most studies examining death-censored graft failure identified AMR as an independent risk factor. Few reported refractory AMR rates or outcomes, and none examined costs. Most studies were single-center and varied greatly in design. Cohort studies of kidney transplant recipients demonstrate that AMR is common and associated with increased risk of death-censored graft failure, but studies vary widely regarding populations, definitions, and reported incidence. Gaps remain in our understanding of refractory AMR, its costs, and resulting quality of life.

Defining a minimal clinically meaningful difference in 12-month estimated glomerular filtration rate for clinical trials in deceased donor kidney transplantation.

BackgroundA Minimal Clinically Meaningful Difference (MCMD) has not been defined for Estimated glomerular filtration rate (eGFR). Our goal was to define the MCMD for eGFR anchored to kidney graft failure.MethodsA systematic review of studies with 12‐month eGFR and subsequent renal graft failure was conducted. For observational studies, we calculated hazard ratio (HR) differences between adjacent eGFR intervals weighted by population distribution. Interventional trials yielded therapeutically induced changes in eGFR and failure risk. OPTN data analysis divided 12‐month eGFR into bands for Cox regressions comparing adjacent eGFR bands with a death‐censored graft survival outcome.ResultsObservational studies indicated that lower eGFR was associated with increased death‐censored graft failure risk; each 5 ml/min/1.73 m2 12‐month eGFR band associated with a weighted incremental HR = 1.12 to 1.23. Clinical trial data found a 5 ml/min/1.73 m2 difference was associated with incremental HR = 1.16 to 1.35. OPTN analyses showed weighted mean HRs across 10, 7, and 5 ml/min/1.73 m2 bands of 1.47, 1.30, and 1.19.ConclusionsA 5 ml/min/1.73 m2 difference in 12‐month eGFR was consistently associated with ~20% increase in death‐censored graft failure risk. The magnitude of effect has been interpreted as clinically meaningful in other disease states and should be considered the MCMD in renal transplantation clinical trials.

On Path to Informing Hierarchy of Eplet Mismatches as Determinants of Kidney Transplant Loss

IntroductionTo mitigate risks related to human leukocyte antigen (HLA) incompatibility, we assessed whether certain structurally defined HLA targets present in donors but absent from recipients, known as eplet mismatches (EMM), are associated with death-censored graft failure (DCGF).MethodsWe studied a cohort of 118,313 American 0% panel reactive antibodies (PRA) first kidney transplant recipients (2000 to 2015) from the Scientific Registry of Transplant Recipients. Imputed allele-level donor and recipient HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were converted to the repertoire of EMM. We fit survival models for each EMM with significance thresholds corrected for false discovery rate and validated those in an independent PRA > 0% cohort. We conducted network-based analyses to model relationships among EMM and developed models to select the subset of EMM most predictive of DCGF.ResultsOf 412 EMM observed, 119 class I and 118 class II EMM were associated with DCGF. Network analysis showed that although 210 eplets formed profiles of 2 to 12 simultaneously occurring EMMs, 202 were singleton EMMs that were not involved in any profile. A variable selection procedure identified 55 single HLA class I and II EMMs in 70% of the dataset; of those, 15 EMMs (9 singleton and 6 involved in profiles) were predictive of DCGF in the remaining dataset.ConclusionOur analysis distinguished increasingly smaller subsets of EMMs associated with increased risk of DCGF. Validation of these EMMs as important predictors of transplant outcomes (in contrast to acceptable EMMs) in datasets with measured allele-level genotypes will support their role as immunodominant EMMs worthy of consideration in organ allocation schemes.

Outcomes of Delayed Graft Function in Kidney Transplant Recipients Stratified by Histologic Biopsy Findings

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.

Changes in cancer incidence and outcomes among kidney transplant recipients in the United States over a thirty-year period

Recipients of kidney transplants have elevated cancer risk compared with the general population. Improvements over time in transplant care and cancer treatment may have affected incidence and outcomes of cancer among recipients of kidney transplant. To evaluate this, we used linked United States transplant and cancer registry data to study 101,014 adult recipients of kidney transplants over three decades (1987-1996, 1997-2006, 2007-2016). Poisson regression was used to assess trends in incidence for cancer overall and seven common cancers. Associations of cancer with risk of death-censored graft failure (DCGF) and death with functioning graft (DWFG) were evaluated with Cox regression. We also estimated absolute risks of DCGF and graft failure following cancer for recipients transplanted in 2007-2016. There was no significant change in the incidence of cancer overall or for six common cancers in recipients across the 1987-2016 period. Only the incidence of prostate cancer significantly decreased across this period after multivariate adjustment. Among recipients of kidney transplants with non-Hodgkin lymphoma, there were significant declines over time in elevated risks for DCGF and DWFG but no significant changes for other combined cancers. For recipients transplanted in the most recent period (2007-2016), risks following cancer diagnosis remained high, with 38% experiencing DWFG and 14% graft failure within four years of diagnosis. Absolute risk of DWFG was especially high following lung cancer (78%), non-Hodgkin lymphoma (38%), melanoma (35%), and colorectal cancer (49%). Thus, across a 30-year period in the United States, there was no overall change in cancer incidence among recipients of kidney transplants. Despite improvements for non-Hodgkin lymphoma, cancer remains a major cause of morbidity and mortality.

Clinical outcomes associated with long-term exposure to airborne particulate pollution in kidney transplant recipients

We aimed to evaluate the relationship of 10-μm particulate matter (PM10) with the risk of graft failure, mortality, and decline of graft function in kidney transplant recipients (KTRs). Air pollutant data were obtained from the Korean National Institute of Environmental Research and linked to those of 1,532 KTRs who underwent kidney transplantation in tertiary hospital from 2001 to 2015. Survival models were used to evaluate the association of PM10 concentrations and the risk of death-censored graft failure (DCGF), all-cause mortality, and biopsy-proven rejection (BPR) over a median follow-up of 6.31 years. The annual average PM10 exposure after KT was 27.1 ± 8.0 μg/m3. Based on the 5-year baseline exposure, a 1-μg/m3 increase in PM10 concentration was associated with increased risk of DCGF and BPR. All-cause mortality was significantly associated with 5-year average PM10 concentrations before the event in fully adjusted models. Long-term PM10 exposure has a significant association with respect to the risk of BPR, DCGF, and all-cause mortality.

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study.

SummaryIn this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living‐related donor (LRD) or living‐unrelated donor (LUD). Adult patients in the ERA‐EDTA Registry who received their first kidney transplant in 1998–2017 were included. Ten‐year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five‐year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7–4.6) and 10.8% (95% CI: 10.1–11.5) versus 6.5% (95% CI: 5.7–7.4) and 12.2% (95% CI: 11.2–13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87–1.13) for patient survival and 1.03 (95% CI: 0.94–1.14) for graft survival. Unadjusted risk of death‐censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04–1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death‐censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.

Impact of HLA compatibility in recipients of kidneys from expanded criteria donors: A Collaborative Transplant Study Report.

Due to a widespread organ shortage, the use of expanded criteria donors (ECDs) in kidney transplantation has increased persistently, reaching approximately 40% in recent years. Whether human leucocyte antigen (HLA) matching between donor and recipient should be part of allocation algorithms in transplantation of ECD kidneys, and especially of ECD kidneys from ≥70-year-old donors, is still in question. To this end, 135,529 kidney transplantations performed between 2000 and 2017 and reported to the Collaborative Transplant Study were analysed and the impact of HLA-A+B+DR mismatches on death-censored graft and patient survival as well as on rejection episodes was investigated. Results were stratified according to donor status (standard criteria donor (SCD) versus ECD) and age of ECD. HLA incompatibility increased the five-year death-censored graft failure risk similarly strong in recipients of ECD and SCD transplants (hazard ratio (HR) per HLA mismatch 1.078 and 1.075, respectively; p<.001 for both). Its impact on rejection treatments during the first post-transplant year was also significant but slightly weaker for recipients of ECD transplants (risk ratio (RR) per HLA mismatch 1.10 for ECD transplants and 1.13 for SCD transplants; p<.001 for both). Mortality increased gradually from zero to six HLA mismatches in recipients of SCD transplants, whereas for ECD transplants a significant increase was notable only from zero to more than zero mismatches. A significant but slightly less pronounced impact of HLA incompatibility on graft failure was observed in transplants from ≥70- compared with <70-year-old ECDs (HR per mismatch 1.047 and 1.093; p=.009 and<0.001, respectively). The influence of HLA mismatches on rejection treatments was the same for both ECD age groups (RR=1.10, p<.001 and p=.004, respectively). Our data indicate that HLA matching should be part of allocation algorithms not only in transplantation of kidneys from SCDs but also from ECDs.

Characterizing the landscape and impact of infections following kidney transplantation.

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3months, 53.7% at 1year, and 78.0% at 5years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P<.001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: 2.15 2.222.29 , P<.001) and 1.92-fold higher DCGF risk (aHR: 1.84 1.911.98 , P<.001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks.

P1634TIME-UPDATED SERUM CALCIUM AND PHOSPHATE ARE ASSOCIATED WITH GRAFT AND PATIENT OUTCOMES AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Disturbances in calcium-phosphate homeostasis are common after kidney transplantation. The clinical implications of changes in calcium-phosphate homeostasis after transplantation are unclear. The aim of this study was to assess the relationship between time-updated serum calcium and phosphate levels and subsequent graft and patient outcomes. Method Kidney transplant recipients with ≥2 serum calcium and phosphate measurements were included from a large single-center cohort; only first transplants were considered. Patients with graft failure &amp;lt;3 months were excluded, as were measurements obtained when eGFR was &amp;lt;15 mL/min/1.73m2 or during intensive care unit admission. Normocalcemia was defined as (albumin-corrected) calcium between 2.20 and 2.60 mmol/L (8.8-10.4 mg/dL), and normophosphatemia as 0.70-1.50 mmol/L (2.17-4.64 mg/dL). Time-updated multivariable Cox regression analyses and time-updated restricted cubic splines analyses were performed to assess the relationship between post-KTx serum corrected calcium and phosphate levels and mortality and death-censored graft failure (DCGF). Final models were adjusted for recipient age, sex, BMI, eGFR, proteinuria, systolic BP (all time-updated), antihypertensive drug use, recipient CMV status, donor age, sex, and status (living or post-mortal), cold and warm ischemia times, HLA mismatches, primary kidney disease, and serum phosphate (in calcium analyses) or corrected calcium (in phosphate analyses). Results A total of 2,769 patients with 138,496 serum corrected calcium and phosphate levels post-KTx were included (median [IQR] 43 [31-61] measurements per patient). Mean age was 47 ± 14 yrs, 42.3% was female, and 19% underwent a pre-emptive transplantation. Hypercalcemia was more common in the first year (15%) and declined to ∼5% during long-term follow-up; hypocalcemia occurred in ∼10% throughout. Hypophosphatemia (24.3%) and hyperphosphatemia (15.5%) were particularly common during the first 30 days post-transplant, and stabilized at ∼10% and ∼5% after the first year. During median follow-up of 16.3 (8.7 – 25.2) years, 477 patients (17.2%) developed DCGF and 1050 (37.9%) patients died. In multivariable regression analyses, post-transplant hypocalcaemia was associated with an increased risk of DCGF (fully adjusted hazard ratio [HR] 2.01 [95% CI 1.61-2.50], P&amp;lt;0.0001; Figure 1A), but not mortality (HR 1.06 [95% CI 0.88-1.27], P=0.55; Figure 1B). Post-transplant hypercalcaemia was associated with an increased risk of mortality (HR 1.77 [95% CI 1.44-2.17], P&amp;lt;0.0001), but not DCGF (HR 0.79 [95% CI 0.48-1.32], P=0.37). Patients with post-KTx hyperphosphatemia were at increased risk of both DCGF (HR 37.12 [95% CI 30.33-45.42], P&amp;lt;0.0001; Figure 1C) and mortality (HR 3.17 [95% CI 1.65-3.86], P&amp;lt;0.0001; Figure 1D). Patients with hypophosphataemia had a lower risk of developing DCGF (HR 0.48 [95% CI 0.28-0.81], P&amp;lt;0.01), but not mortality (HR 0.92 [95% CI 0.72-1.18], P=0.42). Similar results were obtained in sensitivity analyses in a subgroup with parathyroid hormone data available (N=1,412) or after exclusion of the highest and lowest 0.5% of calcium or phosphate levels. Conclusion Post-transplant hypocalcaemia and hyperphosphatemia are associated with an increased risk of DCGF, while hypophosphataemia was linked with a lower DCGF risk. Hypercalcaemia and hyperphosphataemia were associated with an increased mortality risk. These findings underline the relevance of keeping calcium and phosphate within normal range after kidney transplantation.