Risk Of Death-censored Graft Failure Research Articles

Patient and Kidney Allograft Survival with National Kidney Paired Donation.

In the United States, kidney paired donation networks have facilitated an increasing proportion of kidney transplants annually, but transplant outcome differences beyond 5 years between paired donation and other living donor kidney transplant recipients have not been well described. Using registry-linked data, we compared National Kidney Registry (n=2363) recipients to control kidney transplant recipients (n=54,497) (February 2008 to December 2017). We estimated the risk of death-censored graft failure and mortality using inverse probability of treatment weighted Cox regression. The parsimonious model adjusted for recipient factors (age, sex, black, race, body mass index ≥30 kg/m2, diabetes, previous transplant, preemptive transplant, public insurance, hepatitis C, eGFR, antibody depleting induction therapy, year of transplant), donor factors (age, sex, Hispanic ethnicity, body mass index ≥30 kg/m2), and transplant factors (zero HLA mismatch). National Kidney Registry recipients were more likely to be women, black, older, on public insurance, have panel reactive antibodies >80%, spend longer on dialysis, and be previous transplant recipients. National Kidney Registry recipients were followed for a median 3.7 years (interquartile range, 2.1-5.6; maximum 10.9 years). National Kidney Registry recipients had similar graft failure (5% versus 6%; log-rank P=0.2) and mortality (9% versus 10%; log-rank P=0.4) incidence compared with controls during follow-up. After adjustment for donor, recipient, and transplant factors, there no detectable difference in graft failure (adjusted hazard ratio, 0.95; 95% confidence interval, 0.77 to 1.18; P=0.6) or mortality (adjusted hazard ratio, 0.86; 95% confidence interval, 0.70 to 1.07; P=0.2) between National Kidney Registry and control recipients. Even after transplanting patients with greater risk factors for worse post-transplant outcomes, nationalized paired donation results in equivalent outcomes when compared with control living donor kidney transplant recipients.

Epitopes as characterized by antibody-verified eplet mismatches determine risk of kidney transplant loss

To optimize strategies that mitigate the risk of graft loss associated with HLA incompatibility, we evaluated whether sequence defined HLA targets (eplets) that result in donor-specific antibodies are associated with transplant outcomes. To define this, we fit multivariable Cox proportional hazard models in a cohort of 118 382 United States first kidney transplant recipients to assess risk of death-censored graft failure by increments of ten antibody-verified eplet mismatches. To verify robustness of our findings, we conducted sensitivity analysis in this United States cohort and assessed the role of antibody-verified eplet mismatches as autonomous predictors of transplant glomerulopathy in an independent Canadian cohort. Antibody-verified eplet mismatches were found to be independent predictors of death-censored graft failure with hazard ratios of 1.231 [95% confidence interval 1.195, 1. 268], 1.268 [1.231, 1.305] and 1.411 [1.331, 1.495] for Class I (HLA-A, B, and C), -DRB1 and -DQB1 loci, respectively. To address linkage disequilibrium between HLA-DRB1 and -DQB1, we fit models in a subcohort without HLA-DQB1 eplet mismatches and found hazard ratios for death-censored graft failure of 1.384 [1.293, 1.480] for each additional antibody-verified HLA-DRB1 eplet mismatch. In a subcohort without HLA-DRB1 mismatches, the hazard ratio was 1.384 [1.072, 1.791] for each additional HLA-DQB1 mismatch. In the Canadian cohort, antibody-verified eplet mismatches were independent predictors of transplant glomerulopathy with hazard ratios of 5.511 [1.442, 21.080] for HLA-DRB1 and 3.640 [1.574, 8.416] for -DRB1/3/4/5. Thus, donor-recipient matching for specific HLA eplets appears to be a feasible and clinically justifiable strategy to mitigate risk of graft loss.

Cannabis Dependence or Abuse in Kidney Transplantation: Implications for Posttransplant Outcomes.

Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications is increasing. Policies and guidance on cannabis use in transplant patients remain controversial. We examined a database linking national kidney transplant records (n = 52 689) with Medicare claims to identify diagnoses of cannabis dependence or abuse (CDOA) and associations [adjusted hazard ratio (aHR) with 95% upper and lower confidence limits (CLs)] with graft, patient, and other clinical outcomes. CDOA was diagnosed in only 0.5% (n = 254) and 0.3% (n = 163) of kidney transplant recipients in the years before and after transplant, respectively. Patients with pretransplant CDOA were more likely to be 19 to 30 years of age and of black race, and less likely to be obese, college-educated, and employed. After multivariate and propensity adjustment, CDOA in the year before transplant was not associated with death or graft failure in the year after transplant, but was associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance, schizophrenia, and depression. Furthermore, CDOA in the first year posttransplant was associated with an approximately 2-fold increased risk of death-censored graft failure (aHR, 2.29; 95% CL, 1.59-3.32), all-cause graft loss (aHR, 2.09; 95% CL, 1.50-2.91), and death (aHR, 1.79; 95% CL, 1.06-3.04) in the subsequent 2 years. Posttransplant CDOA was also associated with cardiovascular, pulmonary, and psychosocial problems, and with events such as accidents and fractures. Although associations likely, in part, reflect associated conditions or behaviors, clinical diagnosis of CDOA in the year after transplant appears to have prognostic implications for allograft and patient outcomes. Recipients with posttransplant CDOA warrant focused monitoring and support.

The temporal and long-term impact of donor body mass index on recipient outcomes after kidney transplantation - a retrospective study.

The impact of increasing body mass index (BMI) on development and progression of chronic kidney disease is established. Even implantation kidney biopsies from obese living donors demonstrate subtle histologic changes despite normal function. We hypothesized that kidneys from obese living (LD) and deceased donors (DD) would have inferior long-term allograft outcomes. In a study utilizing US transplant registry, we studied adult kidney transplant recipients from 2000 to 2014. Donors were categorized as BMI <20 (underweight), 20-25 (normal), 25-30 (overweight), 30-35 (mildly obese), and >35kg/m2 (very obese). Our outcome of interest was death censored graft failure (DCGF). Cox proportional hazards model were fitted separately for recipients of DD and LD kidneys, and adjusted for donor, recipient, and transplant characteristics, including donor and recipient size mismatch ratio. Among 118734 DD and 84377 LD transplants recipients, we observed a significant and graded increase in DCGF risk among the overweight (LD:HR=1.06, DD:HR=1.04), mildly obese (LD:HR=1.16, DD:HR=1.10), and very obese (LD:HR=1.22, DD:HR=1.22) compared to normal BMI (P<0.05). The graded effect of donor BMI on outcomes begins early and persists throughout the post-transplant period. Donor obesity status is an independent risk factor for inferior long-term renal allograft outcome despite adjusting for donor and recipient size mismatch and other donor, recipient, and transplant factors.

Kidney transplant outcomes in recipients with visual, hearing, physical and walking impairments: a prospective cohort study.

Disability in general has been associated with poor outcomes in kidney transplant (KT) recipients. However, disability can be derived from various components, specifically visual, hearing, physical and walking impairments. Different impairments may compromise the patient through different mechanisms and might impact different aspects of KT outcomes. In our prospective cohort study (June 2013-June 2017), 465 recipients reported hearing, visual, physical and walking impairments before KT. We used hybrid registry-augmented Cox regression, adjusting for confounders using the US KT population (Scientific Registry of Transplant Recipients, N = 66891), to assess the independent association between impairments and post-KT outcomes [death-censored graft failure (DCGF) and mortality]. In our cohort of 465 recipients, 31.6% reported one or more impairments (hearing 9.3%, visual 16.6%, physical 9.1%, walking 12.1%). Visual impairment was associated with a 3.36-fold [95% confidence interval (CI) 1.17-9.65] higher DCGF risk, however, hearing [2.77 (95% CI 0.78-9.82)], physical [0.67 (95% CI 0.08-3.35)] and walking [0.50 (95% CI 0.06-3.89)] impairments were not. Walking impairment was associated with a 3.13-fold (95% CI 1.32-7.48) higher mortality risk, however, visual [1.20 (95% CI 0.48-2.98)], hearing [1.01 (95% CI 0.29-3.47)] and physical [1.16 (95% CI 0.34-3.94)] impairments were not. Impairments are common among KT recipients, yet only visual impairment and walking impairment are associated with adverse post-KT outcomes. Referring nephrologists and KT centers should identify recipients with visual and walking impairments who might benefit from targeted interventions pre-KT, additional supportive care and close post-KT monitoring.

Higher immunoglobulinA nephropathy recurrence in related-donor kidney transplants: The Japan Academic Consortium of Kidney Transplantation study.

To investigate the 10-year biopsy-proven recurrence rates and risk factors for immunoglobulinA nephropathy recurrence in kidney transplant recipients. We included 299 kidney transplant recipients from 1995 to 2015, who had biopsy-proven underlying immunoglobulinA nephropathy and underwent zero-hour biopsy. The primary end-point was recurrence of immunoglobulinA nephropathy. We compared clinical, treatment and graft failure among those with and without recurrent immunoglobulinA nephropathy. A time-to-recurrence analysis was carried out using the competing risk analysis and time-dependent Cox model. Of 299 recipients, 80 had recurrent immunoglobulinA nephropathy (66.3% with clinical biopsy and 33.7% with protocol biopsy, post-transplant biopsy rate: 90.6%). The 10-year recurrence rate was 34.3% (95% confidence interval 27.6-41.1). Related-donor transplantation (hazard ratio 2.28, P=0.009) and post-transplant increased proteinuria (hazard ratio 1.59, P<0.001) were identified as potential risk factors for immunoglobulinA nephropathy recurrence. The 10-year rates were 41.5% in related donor recipients and 16.3% in unrelated donor recipients. There was no conclusive evidence that the calcineurin inhibitor, antimetabolites, basiliximab and rituximab reduce immunoglobulinA nephropathy recurrence. ImmunoglobulinA nephropathy recurrence was associated with an increased risk of death-censored graft failure (hazard ratio 5.29, 95% confidence interval 1.39-20.17, P=0.015). However, related donor itself was not associated with an increased risk of graft failure. The present results have clinical implications in that the signs of recurrent immunoglobulinA nephropathy should be evaluated carefully in recipients receiving related-donor transplants. There is a need for further studies related to genetic and/or familial interactions in kidney transplant recipients with immunoglobulinA nephropathy and related donors.

SUN-120 POST-TRANSPLANT ARSENIC AND THE RISK OF DEATH-CENSORED GRAFT FAILURE IN RENAL TRANSPLANT RECIPIENTS

Arsenic exposure leads to nephrotoxicity, renal fibrosis, and progressive decline in renal function. To date, however, no study has been devoted to evaluate the association between arsenic exposure and renal allograft failure. We investigated the prospective association between circulating arsenic and risk of graft failure in a large cohort of renal transplant recipients (RTRs) with long-term follow-up. Blood arsenic concentrations were measured in an extensively phenotyped cohort of RTRs. Dietary intake was assessed using a validated 177-item food Food Frequency Questionnaire. Backward linear regression analyses were performed to identify determinants of circulating arsenic concentrations. Associations of circulating arsenic concentrations with incident death-censored graft failure were assessed using Cox-proportional hazards regressions analyses. We included 665 RTRs (53 ± 13 years-old, 58% men). The median (interquartile range) arsenic concentration was 1.26 (1.04 - 2.04) ng/mL. Backward linear regression analyses showed that fish consumption and estimated Glomerular Filtration Rate (eGFR) were the major determinants of circulating arsenic concentrations (std. β = 0.22; P-value = 0.001; and, std. β = ─0.19; P-value = 0.003, respectively). At 5 years of follow-up, 72 (11%) patients had developed graft failure. In multivariable Cox regression analyses, circulating arsenic was positively associated with risk of death-censored graft failure (hazard ratio, 1.59; 95% confidence interval, 1.10 to 2.30 per 1 ng/mL higher circulating arsenic concentration), independent of several potential confounders including transplant- and graft failure-related risk factors. Similar findings were found at 4 and 3 years of follow-up (respectively, hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; and, hazard ratio, 1.64; 95% confidence interval, 1.02 to 2.64, per 1 ng/mL higher circulating arsenic concentration). Table 1Prospective analyses of the association of circulating arsenic with death-censored graft failure in 665 RTRs at 5-, 4-, and 3-years of follow-upCirculating arsenic, ng/mL3-yrs of follow-up4-yrs of follow-up5-yrs of follow-upHR95%CIHR95%CIHR95%CIEvents, n455672Model 11.481.00─2.171.471.04─2.091.471.08─2.01Model 21.851.22─2.811.891.30─2.761.791.28─2.51Model 31.761.14─2.711.721.16─2.561.771.24─2.53Model 41.641.02─2.641.751.15─2.661.591.10─2.30 Open table in a new tab Model 1: crude. Model 2: adjusted for fish intake. Model 3: model 2 + adjustment for donor age, recipient age, donor type, time since transplantation and baseline, immunosuppressive therapy. Model 4: model 2 + adjustment for eGFR, systolic blood pressure, total cholesterol and triglycerides concentration, history of diabetes, homocysteine, and hs-CRP. The association of post-transplant arsenic exposure with renal allograft outcomes has long been overlooked in clinical research. These data show for the first time that relatively higher post-transplant circulating arsenic concentrations are independently associated with higher long-term risk of graft failure in RTRs.

Association between post-transplant serum uric acid levels and kidney transplantation outcomes.

BackgroundSerum uric acid (UA) level has been reported to be associated with chronic allograft nephropathy and graft failure in patients who undergo kidney transplantation (KT). However, the role of serum UA level in renal graft survival remains controversial.ObjectiveThis study aimed to investigate the effect of mean serum UA level during two different post-KT periods on long-term renal graft outcomes in a large population cohort in which living donor KT prevails.Material and methodsA retrospective cohort study was performed using KT data prospectively collected at a single institution. Patients (n = 2,993) were divided into low-, normal-, and high-UA groups according to the mean serum UA level within the first year (1-YR) and 1–5 years (5-YR) after transplantation.ResultsIn the 1-YR Cox proportional hazards analysis, the low- and high-UA groups had a significantly decreased and increased risk, respectively, for overall graft failure (OGF), death-censored graft failure (DCGF), and composite event (return to dialysis, retransplantation, death from graft dysfunction, and 40% decline in estimated glomerular filtration rate) compared with the normal-UA group. Similarly, in the 5-YR analysis, the low-UA group had a significantly reduced risk of DCGF compared with the normal-UA group, whereas the high-UA group had a significantly increased risk of all three graft outcomes. In a marginal structural model, hyperuricemia had a significant causal effect on worsening graft outcomes, with consideration of all confounding variables (OGF: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.33–3.78; DCGF: HR 2.38, 95% CI 1.09–4.9; composite event: HR 3.05, 95% CI 1.64–5.49).ConclusionsA low-to-normal serum UA level within the first year and 1–5 years after KT is an independent factor for better renal allograft outcomes in the long-term follow-up period rather than high serum UA level.

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients.

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CES-D score>14) and frailty were associated with KT length of stay (LOS), death-censored graft failure(DCGF), andmortality. AtKTadmission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail(aOR=3.97, 95% CI: 2.28-6.91, P<0.001).Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70-2.08, P<0.001) longer LOS, 6.20-fold (95% CI:1.67-22.95, P<0.01)increased risk of DCGF, and 2.62-fold(95% CI:1.03-6.70, P=0.04)increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction<0.001). Interventions aimed at reducing pre-KT depressive symptoms and frailty should be explored for their impact on post-KT outcomes.

Living donor postnephrectomy kidney function and recipient graft loss: A dose-response relationship.

Development of end-stage renal disease (ESRD) in living kidney donors is associated with increased graft loss in the recipients of their kidneys. Our goal was to investigate if this relationship was reflected at an earlier stage postdonation, possibly early enough for recipient risk prediction based on donor response to nephrectomy. Using national registry data, we studied 29 464 recipients and their donors from 2008-2016 to determine the association between donor 6-month postnephrectomy estimated GFR (eGFR) and recipient death-censored graft failure (DCGF). We explored donor BMI as an effect modifier, given the association between obesity and hyperfiltration. On average, risk of DCGF increased with each 10 mL/min decrement in postdonation eGFR (adjusted hazard ratio [aHR] 1.06, 95% confidence interval [CI] 1.02-1.10, P = .007). The association was attenuated with higher donor BMI (interaction P = .049): recipients from donors with BMI = 20 (aHR 1.12, 95% CI 1.04-1.19, P = .002) and BMI = 25 (aHR 1.07, 95% CI 1.03-1.12, P = .001) had a higher risk of DCGF with each 10 mL/min decrement in postdonation eGFR, whereas recipients from donors with BMI = 30 and BMI = 35 did not have a higher risk. The relationship between postdonation eGFR, donor BMI, and recipient graft loss can inform counseling and management of living donor kidney transplant recipients.

Kidney transplantation in older recipients: Preemptive high KDPI kidney vs lower KDPI kidney after varying dialysis vintage.

AIMTo evaluate the outcomes of transplanting marginal kidneys preemptively compared to better-quality kidneys after varying dialysis vintage in older recipients.METHODSUsing OPTN/United Network for Organ Sharing database from 2001-2015, we identified deceased donor kidney (DDK) transplant recipients > 60 years of age who either underwent preemptive transplantation of kidneys with kidney donor profile index (KDPI) ≥ 85% (marginal kidneys) or received kidneys with KDPI of 35%-84% (better quality kidneys that older wait-listed patients would likely receive if waited longer) after being on dialysis for either 1-4 or 4-8 years. Using a multivariate Cox model adjusting for donor, recipient and transplant related factors- overall and death-censored graft failure risks along with patient death risk of preemptive transplant recipients were compared to transplant recipients in the 1-4 and 4-8 year dialysis vintage groups.RESUTLSThe median follow up for the whole group was 37 mo (interquartile range of 57 mo). A total of 6110 DDK transplant recipients above the age of 60 years identified during the study period were found to be eligible to be included in the analysis. Among these patients 350 received preemptive transplantation of kidneys with KDPI ≥ 85. The remaining patients underwent transplantation of better quality kidneys with KDPI 35-84% after being on maintenance dialysis for either 1-4 years (n = 3300) or 4-8 years (n = 2460). Adjusted overall graft failure risk and death-censored graft failure risk in preemptive high KDPI kidney recipients were similar when compared to group that received lower KDPI kidney after being on maintenance dialysis for either 1-4 years (HR 1.01, 95%CI: 0.90-1.14, P = 0.84 and HR 0.96, 95%CI: 0.79-1.16, P = 0.66 respectively) or 4-8 years (HR 0.82, 95%CI: 0.63-1.07, P = 0.15 and HR 0.81, 95%CI: 0.52-1.25, P = 0.33 respectively). Adjusted patient death risk in preemptive high KDPI kidney recipients were similar when compared to groups that received lower KDPI kidney after being on maintenance dialysis for 1-4 years (HR 0.99, 95%CI: 0.87-1.12, P = 0.89) but lower compared to patients who were on dialysis for 4-8 years (HR 0.74, 95%CI: 0.56-0.98, P = 0.037).CONCLUSIONIn summary, our study supports accepting a “marginal” quality high KDPI kidney preemptively in older wait-listed patients thus avoiding dialysis exposure.

Glomerular crescents are associated with worse graft outcome in allograft IgA nephropathy.

The prognosis of patients with allograft IgA nephropathy (IgAN) requires further investigation. We performed a bicenter retrospective cohort study on kidney transplant recipients diagnosed with IgAN in allograft biopsy. Recipients without allograft IgAN but with known IgAN before transplantation were included as the control group. We investigated the associations between clinicopathological characteristics, including allograft crescents, and the risk of death-censored graft failure. In total, 1256 IgAN patients in both pre- and posttransplant stages were included. Among them, 559 were diagnosed with allograft IgAN, which was a time-dependent risk factor for worse prognosis (adjusted hazard ratio =5.009 [3.610-6.951]; P<.001) during a median of 8.1years of follow-up. Of the patients with allograft IgAN, 88 (15.9%) had glomerular crescents, including 40 patients (7.2%) with >10% crescent formation in the total biopsied glomeruli. The presence of glomerular crescents in IgAN was associated with a worse graft prognosis, and the association was still valid with the C scores of the current Oxford classification. In conclusion, allograft IgAN is a time-dependent event and is associated with worse graft outcomes. The pathological characteristics of allograft, particularly the degree of glomerular crescent formation, may represent important risk factors for a poor prognosis.

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes - a retrospective cohort study.

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death-censored graft failure (DCGF). Of 274 KT eligible for analysis, 59% were from expanded criteria donor. RR was modeled as a categorical variable, using a previously identified terminal threshold of 0.4, and 0.2mmHg/ml/min (median in our cohort). Hazard ratios (HR) of DCGF were 3.23 [95% confidence interval (CI): 1.12-9.34, P=0.03] and 2.67 [95% CI: 1.14-6.31, P=0.02] in univariable models, and 2.67 [95% CI: 0.91-7.86, P=0.07] and 2.42 [95% CI: 1.02-5.72, P=0.04] in multivariable models, when RR threshold was 0.4 and 0.2, respectively. Increasing risk of DCGF was observed when RR over the course of HMP was modeled using mixed linear regression models: HR of 1.31 [95% CI: 1.07-1.59, P<0.01] and 1.25 [95% CI: 1.00-1.55, P=0.05], in univariable and multivariable models, respectively. This suggests that RR during HMP is a predictor of long-term KT outcomes. Prospective studies are needed to assess the survival benefit of patients receiving KT with higher RR in comparison with staying wait-listed.

Persistent hyperparathyroidism as a risk factor for long-term graft failure: the need to discuss indication for parathyroidectomy

BackgroundAlthough a successful kidney transplant (KTx) improves most of the mineral and bone disorders (MBD) produced by chronic kidney disease (CKD), hyperparathyroidism may persist (pHPT). Current guidelines recommend parathyroidectomy if serum parathormone is persistently elevated 1 year after KTx, because pHPT has been recently associated with poor graft outcomes. However, whether patients with pHPT and adequate renal function are at risk for long-term graft failure is unknown. MethodsLongitudinal follow-up of 911 adults submitted to KTx between January 2005 and December 2014, with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min 1 year after surgery. Clinical and laboratory data were collected from electronic database. Graft failure was defined as return to dialysis. ResultsOverall, 62% of the patients were classified as having pHPT 1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up, death-censored graft survival was lower in the pHPT group (P = .009), even after adjustment for age at KTx, donor age, donor type, acute rejection, parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR] 1.99; 1.004–3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff to predict pHPT at 1 year (specificity = 92.1%). ConclusionHaving pHPT after a successful KTx increases the long-term risk of death-censored graft failure. This result highlights the need for better recognition and management of CKD-MBD before and during the first year after KTx, and opens a discussion on the more appropriate timing to perform parathyroidectomy.

Antidepressant medication use before and after kidney transplant: implications for outcomes - a retrospective study.

We examined a novel database wherein national US transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008-2015) to characterize antidepressant use before and after kidney transplantation, and associations [adjusted hazard ratio (aHR) 95% CI] with death and graft failure. Among 72 054 recipients, 12.6% filled antidepressant medications in the year before transplant, and use was more common among women and patients who were white, unemployed, and had limited functional status. Pre-transplant antidepressant use was associated with 39% higher 1-year mortality (aHR 1.39, 95% CI 1.18-1.64) and 15% higher all-cause graft loss risk (aHR 1.15, 95% CI 1.02-1.30). More than 50% of patients who filled antidepressants pre-transplant continued fill post-transplant. Antidepressant use in the first year after transplant was associated with twofold higher risk of death (aHR 1.94, 95% CI 1.60-2.35), 38% higher risk of death-censored graft failure, and 61% higher risk of all-cause graft failure in the subsequent year. Pre-listing antidepressant use was also associated with increased mortality, but transplantation conferred a survival benefit regardless of prelisting antidepressant use status. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.

Post-Transplant Hypophosphatemia and the Risk of Death-Censored Graft Failure and Mortality after Kidney Transplantation.

Hypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up. We performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure. The median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61). Post-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes.

Role of steroid maintenance in sensitized kidney transplant recipients.

To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance (CSM) emerge. Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal (ESW) among patients who underwent deceased-donor kidney (DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody (peak-PRA) titers (0%-30%, 31%-60% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF). The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure (HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patient-death (HR 1.29, 95%CI: 1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk (HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM (n = 25218) vs ESW (n = 7399). Over-all (HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored (HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk (HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM (n = 3495) vs ESW (n = 850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted overall graft-failure (HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patient-death (HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower (HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM (n = 4966) vs ESW (n = 923). In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.

Transplantation Results of Completely HLA-Mismatched Living and Completely HLA-Matched Deceased-Donor Kidneys Are Comparable

Human leukocyte antigen (HLA) mismatches are known to influence graft survival in deceased-donor kidney transplantation. We studied the effect of HLA mismatches in a population of recipients of deceased-donor or living-donor kidney transplantations. All 1998 transplantations performed in our center between 1990 and 2011 were included in this retrospective cohort study. Four different multivariable Cox proportional hazard analyses were performed with HLA mismatches as continuous variable, as categorical variable (total number of HLA mismatches), as binary variable (zero vs. nonzero HLA mismatches), and HLA-A, -B, and -DR mismatches included separately. Nine hundred ninety-one patients received a deceased-donor kidney and 1007 received a living-donor kidney. In multivariable Cox analysis, HLA mismatches, recipient age, current panel-reactive antibodies, transplant year, donor age, calcineurin inhibitor treatment, and donor type were found to have a significant and independent influence on the risk of graft failure, censored for death. Variables representing the total number of HLA-A, -B, and -DR mismatches had a significant and comparable influence in all analyses. The influence of HLA mismatches on death-censored graft survival holds true for both deceased- and living-donor kidney transplantation. However, the relative risk of death-censored graft failure of a 2-2-2 mismatched living-donor kidney is comparable with that of a 0-0-0 mismatched deceased-donor kidney.

Outcomes of Kidney Transplantation From Older Living Donors

The disparity between donor kidney availability and demand has increased utilization of kidneys from older living donors (OLD). We compared graft and patient outcomes of patients on maintenance dialysis after transplantation with OLD kidneys to those receiving younger live donor (YLD) kidneys and deceased donor (DD) kidneys. Using Australia and New Zealand Dialysis and Transplant Registry, primary live and deceased donor renal transplant recipients aged 18 years or older between 1997 and 2009 were stratified into six groups: standard criteria deceased donor kidneys with total ischemic time of less than 12 hours (SCD, <12), SCD of 12 or greater, expanded criteria donor (ECD) less than 12, ECD of 12 or greater, YLD (LD, <60 years), and OLD kidneys (LD, ≥60 years). Preemptive and multiple-organ transplants were excluded. Of the 6,317 renal transplant recipients, 346 (5.5%) received OLD kidneys. Compared with kidneys from SCD of less than 12 hours, OLD kidneys were associated with a greater risk of death-censored graft failure (DCGF; adjusted HR 2.00; 95% confidence interval, 1.32-3.03) and inferior 5-year graft function (estimated glomerular filtration rate of 45 mL/min vs. 56 mL/min), although no increase in 5-year mortality (HR, 1.18; 95% confidence interval, 0.80-1.76). Outcomes for OLD kidneys were also inferior to YLD recipients, although modestly superior to ECD kidneys. Chronic allograft nephropathy was more commonly reported as the cause of DCGF among recipients of OLD kidneys than other donor types. Patient survival was equal, but graft outcomes for recipients of OLD kidneys were inferior to those obtained with YLD and SCD kidneys. This study suggests that OLD kidneys should be utilized cautiously, cognizant of the fact that younger recipients may have a life expectancy in excess of the life of the transplanted kidney.

Older and Hypertensive Live Donors Associated with a Greater Risk of Death-Censored Graft Failure Compared to Standard Criteria Deceased Donor in Kidney Transplantation

Aims: There has been a significant increase in the utilization of both older live donor (OLD) and expanded criteria (ECD) deceased donor (DD) kidneys for transplantation. Although it is well established that DD-ECD transplants are associated with inferior graft outcomes, transplant outcomes of OLD kidneys remain unclear. Methods: Using the Australia and New Zealand Dialysis and Transplant Registry, primary LD and DD renal transplant recipients in Australia and New Zealand between 1997 and 2009 were analysed. Donor type was categorized into 6 groups - DD-standard criteria with ischaemic time < 12 hours (DD-SCD < 12h), DD-SCD312h, DD-ECD < 12h, DD-ECD 312h, LD-SCD and OLD. DD-ECD were defined as donor age >60 years or age >50 years with 2 of 3 criteria of hypertension, cerebrovascular disease-associated death and terminal creatinine of >133mmol/L, whereas OLD were defined as the presence of donor hypertension or donor age >60 years. Multiple organ grafts and pre-emptive transplants were excluded. Confounders including donor (age, gender), recipient (age, gender, body mass index, co-morbidities, cause of end-stage kidney disease, race) and transplant (HLA-mismatches, panel reactive antibodies, transplant era and state/country) associated variables were included. Outcomes assessed included overall graft failure, death-censored graft failure (DCGF) and recipient survival. Results: Of the 6317 recipients included, the number (%) of recipients in each group was 877 (13.8%) in DD-SCD < 12h, 2105 (33.0%) in DD-SCD 312h, 277 (4.3%) in DD-ECD < 12h, 857 (13.4%) in DD-ECD 312h, 1832 (28.7%) in LD-SCD and 369 (5.8%) in OLD groups. Compared to DD-SCD < 12h, DD-ECD < 12h, DD-ECD 312h and OLD grafts were associated with a significantly higher risk of overall graft failure in the unadjusted and adjusted models (adjusted hazard ratio [AHR] 1.43, 95%CI 1.07, 1.91; AHR 1.77, 95%CI 1.45, 2.16; and AHR 1.35, 95%CI 1.01, 1.82 respectively) and DCGF (HR 1.90, 95%CI 1.22, 2.95; HR 2.46, 95%CI 1.79, 3.37; and HR 1.71, 95%CI 1.11, 2.65 respectively). Compared to DD-SCD < 12h, LD-SCD was associated with a significantly lower risk of overall graft failure (HR 0.77, 95%CI 0.64, 0.94) and recipient death (HR 0.60, 95%CI 0.46, 0.77) in the unadjusted model but not significant in the adjusted model (HR 0.90, 95%CI 0.73, 1.10 and HR 0.85, 95%CI 0.64, 2.22 respectively). Conclusion: With the continuing shortage of organ donors and increasing acceptance of marginal kidneys, the finding of inferior graft outcome of both DD-ECD and OLD grafts compared to DD-SCD and LD-SCD grafts should be carefully considered in the decision-making process for any potential transplant recipient.