Risk Of Death-censored Graft Loss Research Articles

Consequences of Nephrotic Proteinuria and Nephrotic Syndrome after Kidney Transplant.

Proteinuria is the main predictor of kidney graft loss. However, there is little information regarding the consequences of nephrotic proteinuria (NP) and nephrotic syndrome (NS) after a kidney transplant. We aimed to describe the clinical and histopathological characteristics of kidney recipients with nephrotic-range proteinuria and compare the graft surveillance between those who developed NS and those who did not. A total of 204 patients (18.6% of kidney transplants in the study period) developed NP, and 68.1% of them had NS. Of the 110 patients who underwent a graft biopsy, 47.3% exhibited ABMR, 21.8% the recurrence of glomerulonephritis, 9.1% IFTA, and 7.3% de novo glomerulonephritis. After a median follow-up of 97.5 months, 64.1% experienced graft loss. The graft survival after the onset of NP declined from 75.8% at 12 months to 38% at 5 years, without significant differences between those with and those without NS. Patients who developed NS fewer than 3 months after the onset of NP exhibited a significantly higher risk of death-censored graft loss (HR: 1.711, 95% CI: 1.147-2.553) than those without NS or those with late NS. In conclusion, NP and NS are frequent conditions after a kidney transplant, and they imply extremely poor graft outcomes. The time from the onset of NP to the development of NS is related to graft survival.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. During a median follow-up of 119months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.

Association of Postoperative Delirium With Incident Dementia and Graft Outcomes Among Kidney Transplant Recipients.

Kidney transplant (KT) recipients have numerous risk factors for delirium, including those shared with the general surgical population (eg, age and major surgery) and transplant-specific factors (eg, neurotoxic immunosuppression medications). Evidence has linked delirium to long-term dementia risk in older adults undergoing major surgery. We sought to characterize dementia risk associated with post-KT delirium. Using the United States Renal Data System datasets, we identified 35 800 adult first-time KT recipients ≥55 y. We evaluated risk factors for delirium using logistic regression. We evaluated the association between delirium and incident dementia (overall and by subtype: Alzheimer's, vascular, and other/mixed-type), graft loss, and death using Fine and Gray's subhazards models and Cox regression. During the KT hospitalization, 0.9% of recipients were diagnosed with delirium. Delirium risk factors included age (OR = 1.40, 95% CI, 1.28-1.52) and diabetes (OR = 1.38, 95% CI, 1.10-1.73). Delirium was associated with higher risk of death-censored graft loss (aHR = 1.52, 95% CI, 1.12-2.05) and all-cause mortality (aHR = 1.53, 95% CI, 1.25-1.89) at 5 y post-KT. Delirium was also associated with higher risk of dementia (adjusted subhazard ratio [aSHR] = 4.59, 95% CI, 3.48-6.06), particularly vascular dementia (aSHR = 2.51, 95% CI, 1.01-6.25) and other/mixed-type dementia (aSHR = 5.58, 95% CI, 4.24-7.62) subtypes. The risk of all-type dementia associated with delirium was higher for younger recipients aged between 55 and 64 y ( Pinteraction = 0.01). Delirium is a strong risk factor for subsequent diagnosis of dementia among KT recipients, particularly those aged between 55 and 64 y at the time of transplant. Patients experiencing posttransplant delirium might benefit from early interventions to enhance cognitive health and surveillance for cognitive impairment to enable early referral for dementia care.

CYP3A5 Expressor Genotype of the Transplanted Kidney Increases the Risk of Preterm Graft Loss and Acute Rejection

Introduction: Tacrolimus is metabolized mainly in the liver by the CYP3A enzyme family, with a particularly well-documented role of CYP3A5. CYP3A5 is also expressed in the renal tissue and is present in the transplanted kidney. To date, the association between donor CYP3A5 polymorphisms and transplant outcome remains poorly understood. The aim of this study was to assess the effect of donor CYP3A5 expression on early and long-term transplant outcomes. Methods: A retrospective cohort study including 207 patients who received kidney grafts from 110 deceased donors was conducted at a single Central European Center. Tissue samples from all donors were studied for CYP3A5 single-nucleotide polymorphism (rs776746). Death-censored graft loss within 5-year follow-up, acute rejection occurrence, and kidney function, measured using serum creatinine and MDRD eGFR, were compared between groups of patients with allografts from rs776746 carriers (CYP3A5 expressors) and noncarriers (CYP3A5 nonexpressors). Results: Recipients who received kidneys from CYP3A5 expressors (n = 24) were at significantly higher risk of death-censored graft loss within 5-year follow-up (adjusted HR, 95% CI: 6.82, 2.01–23.12; p = 0.002) and acute rejection within the 1st posttransplant year (adjusted OR, 95% CI: 4.62, 1.67–12.77; p = 0.003) than those who did not (n = 183). The median time to loss of function was 1.93 [IQR; 0.77–3.19] years. Conclusions: Donor CYP3A5 expressor status is associated with worse renal graft survival and a higher risk of acute rejection. Determination of donor CYP3A5 genotype is a potentially useful tool that may improve kidney transplant outcomes.

Lower Time in Therapeutic Range Relates to a Worse Kidney Graft Outcome

Tacrolimus has a narrow therapeutic margin. Maintaining tacrolimus blood levels in the appropriate range is difficult because of its intrapatient variability. In fact, greater blood level variability has been related to worse kidney graft outcome, but only measuring variability does not consider the therapeutic range goal. Determining the time in therapeutic range (TTR) using the Rosendaal method allows dose optimization by considering the adverse events associated with both supratherapeutic and subtherapeutic doses. Some previous studies in kidney and lung transplantation have shown that the measurement of TTR has been related to the subsequent graft outcome. We performed a single-center, observational study including 215 consecutive kidney transplants performed in our center. The percentage of time that the patient remained with levels above 6 ng/mL between months 3 and 12 (%TTR3-12) was calculated using the Rosendaal method. A lower %TTR3-12 was associated with a higher risk of acute rejection (area under the receiver operating characteristic curve, 0.614; 95% confidence interval [CI], 0.513-0.714; P=.018) and with a higher risk of having a 1-year glomerular filtration rate < 30 mL/min/1.73 m2 (area under the receiver operating characteristic curve, 0.676; 95% CI, 0.542-0.811; P=.014). The lowest tertile of %TTR3-12 was independently associated with a higher risk of death-censored graft loss (hazard ratio, 10.773; 95% CI, 1.315-88.264; P=.027) after adjusting by 1-year glomerular filtration rate, expanded criteria donation, and acute rejection throughout the first year. To conclude, measuring TTR after kidney transplant is an easy way to estimate the time of exposure to adequate levels of tacrolimus and relates to kidney graft outcome.

Hyperparathyroidism at 1 year after kidney transplantation is associated with graft loss

BackgroundHyperparathyroidism persists in many patients after kidney transplantation. The purpose of this study was to evaluate the association between post-transplant hyperparathyroidism and kidney transplantation outcomes. MethodsWe identified 824 participants from a prospective longitudinal cohort of adult patients who underwent kidney transplantation at a single institution between December 2008 and February 2020. Parathyroid hormone levels before and after kidney transplantation were abstracted from medical records. Post-transplant hyperparathyroidism was defined as parathyroid hormone level ≥70 pg/mL 1 year after kidney transplantation. Cox proportional hazards models were used to estimate the adjusted hazard ratios of mortality and death-censored graft loss by post-transplant hyperparathyroidism. Models were adjusted for age, sex, race/ethnicity, college education, parathyroid hormone level before kidney transplantation, cause of kidney failure, and years on dialysis before kidney transplantation. A Wald test for interactions was used to evaluate the risk of death-censored graft loss by age, sex, and race. ResultsOf 824 recipients, 60.9% had post-transplant hyperparathyroidism. Compared with non-hyperparathyroidism patients, those with post-transplant hyperparathyroidism were more likely to be Black (47.2% vs 32.6%), undergo dialysis before kidney transplantation (86.9% vs 76.6%), and have a parathyroid hormone level ≥300 pg/mL before kidney transplantation (26.8% vs 9.5%) (all P < .001). Patients with post-transplant hyperparathyroidism had a 1.6-fold higher risk of death-censored graft loss (adjusted hazard ratio = 1.60, 95% confidence interval: 1.02–2.49) compared with those without post-transplant hyperparathyroidism. This risk more than doubled in those with parathyroid hormone ≥300 pg/mL 1 year after kidney transplantation (adjusted hazard ratio = 4.19, 95% confidence interval: 1.95–9.03). The risk of death-censored graft loss did not differ by age, sex, or race (all Pinteraction > .05). There was no association between post-transplant hyperparathyroidism and mortality. ConclusionThe risk of graft loss was significantly higher among patients with post-transplant hyperparathyroidism when compared with patients without post-transplant hyperparathyroidism.

On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes.

Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor–recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA−). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA− and LR_dnDSA+/HR_dnDSA− (logRank < 0.001), and higher risk of death-censored graft loss (logRank = 0.001). Both LR_dnDSA+ (HR: 3.51, 95% CI = 1.25–9.85) and LR_dnDSA+/HR_dnDSA+ (HR: 4.09, 95% CI = 1.45–11.54), but not LR_dnDSA+/HR_dnDSA− independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes.

The Role of Donor Sex in Females Undergoing Repeat Kidney Transplant: Does Prior Donor Sex Matter?

We performed a cohort study of adult female recipients undergoing a second kidney transplant (2000-2017), identified using the Scientific Registry of Transplant Recipients. Using multivariable Cox models, we analyzed the risk of death-censored graft loss (DCGL) if the second transplant was from a male versus female kidney donor, conditional on donor sex at the time of the first transplant. In a secondary analysis, we stratified results by recipient age (>50 or ≤50 y) at the time of retransplant. Of 5594 repeat kidney transplants, 1397 (25.0%) developed DCGL. Overall, there was no association between first and second donor sex pairing and DCGL. A prior and current female donor (FD1FD2) posed a higher risk for DCGL in recipients aged >50 y at second transplant (hazard ratio,≤0.67, confidence interval 0.46-0.98, for all other donor combinations), but posed a lower risk if aged ≤50 y at retransplant (hazard ratio, ≥1.37, confidence interval 1.04-1.80, for all other donor combinations). Overall, past-current donor sex pairing was not associated with DCGL in female recipients undergoing second kidney transplant; however, the risk with a past and current female donor was increased in older, and decreased in younger, female recipients at retransplant.

Can uric acid blood levels in renal transplant recipients predict allograft outcome?

Background Hyperuricemia is common after renal transplantation, especially in those receiving calcineurin inhibitors. Little, however, is known about the relationship between uric acid (UA) levels and allograft outcome. Methods We conducted a retrospective single-center analysis (N = 368) in order to assess UA blood levels post-transplant association with allograft outcome. For this study, a median serum UA level of all measured UA levels from 1 month to 1 year post renal transplantation was calculated. Results Patients were divided into 2 groups based on the median UA level measured between 1 and 12 months post-transplant. Those with median UA level ≥ 7 and ≥ 6 mg/dL (N = 164) versus median UA level < 7 and < 6 mg/dL for men and women respectively (N = 204) had lower GFR values at 1, 3 and 5 years posttransplant (mean GFR ± SD of 43.4 ± 20.6 and 58 ± 19.9 at 3 years post-transplant, p < 0.001). In multivariate models, UA levels were no longer significantly associated with renal allograft function. In a multivariate cox proportional hazard model, UA level was found to be independently associated with increased risk for death-censored graft loss (HR of 1.3, 95% CI 1.0–1.7, p < 0.05 for every increase of 1 mg/dL in UA level). Conclusion Hyperuricemia was found to be associated with increased death- censored graft loss but not with allograft function. Increased UA levels were not found to be an independent predictor of long-term allograft function despite the known association of hyperuricemia with the progression of cardiovascular and renal disease.

PRE-TRANSPLANT HLA ANTIBODIES AND DELAYED GRAFT FUNCTION IN THE CURRENT ERA OF KIDNEY TRANSPLANTATION

Collaborative Transplant Study. Introduction: We reported previously that early adverse events in deceased donor kidney transplantation, such as delayed graft function (DGF) and rejection episodes, are associated with pre-transplant presence of HLA antibodies and that patients with adverse events show significantly impaired graft survival rates. In the meantime, the introduction of sensitive antibody detection techniques is expected to have diminished the involvement of overlooked HLA antibodies in DGF. On the other hand, DGF risk might have increased due to growing use of kidneys from elderly donors. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of HLA antibodies in the new era of transplantation. Methods: 1,724 patients who received a deceased donor kidney transplant during 2008–2017 and on whom a pre-transplant serum sample and the information on immediate function within the first 24 hours after transplantation, dialysis during the first week, and biopsy-proven rejection during the first 3 months were available. Graft survival after day 7 during the first 3 years post-transplant was analyzed by multivariable Cox regression. Predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections during days 8–90 were determined by multivariable logistic regression. DGF was defined as either no graft function during the first 24 hours and/or dialysis during the first week. In 44% of cases, we were informed by the centers on the presence or absence of pre-transplant donor-specific antibodies (DSA) as determined by single antigen technique. Results and Discussion: Donor age ≥50 years, simultaneous presence of HLA class I and II antibodies pre-transplant, diabetes mellitus as original disease, cold ischemia time ≥18 hours, and time on dialysis >5 years were associated with an increased risk of DGF. DGF alone doubled the risk for all cause graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (HR=4.75, P<0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P<0.001) were present prior to transplantation. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1 post-transplant, whereas patients with both DGF and rejection showed the lowest rate of good kidney function. Our data indicate that, in the current era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Conclusion: Patients with DGF require special attention, especially in the presence of HLA antibodies.

Pre-transplant HLA Antibodies and Delayed Graft Function in the Current Era of Kidney Transplantation.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008–2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.

P1724RISK FACTORS FOR BK VIRUS INFECTION AFTER KIDNEY TRANSPLANTATION IN THE CONTEMPORARY ERA: A SINGLE-CENTRE OBSERVATIONAL STUDY

Abstract Background and Aims BK infection remains a risk factor for kidney transplant dysfunction and allograft loss. While many risk factors are reported in the literature, many are from historical cohorts and have never been validated in the contemporary era. The aim of this study was to explore risk factors for BK virus infection in the contemporary era of kidney transplantation and immunosuppression using a well-phenotyped clinical cohort. Method In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between January 1st 2007 and June 30th 2018. BK virus was checked in the context of any transplant dysfunction (indication-based) aligned with UK guidance. Positive BK virus results were defined as &amp;gt;200 copies/ml. Clinical outcomes extracted from electronic hospital records were linked with national datasets. Univariate analysis was undertaken to investigate the association between donor-, recipient- and transplant-related variables and risk for BK virus reactivation. Any variable with a p-value &amp;lt;0.15 in univariate Results Data was analysed for 1,770 kidney transplant recipients with median follow up 5.3 years (IQR 2.7 to 8.7 years). BK virus was associated with (versus without); male sex (8.3% versus 5.3% respectively, p=0.010), ABO-incompatible transplantation (12.7% versus 5.9% respectively, p=0.021) and delayed graft function (9.0% versus 6.3% respectively, p=0.032). In a multivariate analysis, including all variables in univariate analysis with p-value &amp;lt;0.15, the only independent variables associated with BK infection were recipient male sex (OR 2.051 [95% CI 1.196-3.519], p=0.009 and ABO-incompatible transplantation (OR 4.087 {95% CI 1.847-9.042], p=0.001). From an outcome perspective, recipients with BK viraemia had worse graft function at 1-, 3- and 5-year post kidney transplantation but no increased risk for death-censored graft loss. Conclusion In the contemporary era, only recipient male sex and ABO-incompatible kidney transplantation are independently associated with risk for BK infection. Study limitations include lack of data regarding novel risk factors (e.g. BK virus serostatus). Association does not imply causality and we suggest further work is warranted to validate contemporary risk factors for BK infection in different kidney transplant population cohorts.

Retroactive Application of a New Risk Index for Living Donor Kidney Transplantation to Renal Transplants in Veracruz, Mexico

BackgroundThe Living Kidney Donor Profile Index (LKDPI) was recently created. This model predicts recipient risk of graft loss after living donor transplant. Herein, we applied the LDKPI to our population to analyze its performance. MethodsA retrospective analysis of all living donor kidney transplants from 2003 to 2018 from 2 transplant centers in Veracruz, Mexico, was used. LKDPI was calculated in a webpage (www.transplantmodels.com). Donor and recipient demographics and transplant data included in the model were registered. Pearson correlation between the LKDPI percentage and death-censored graft survival was performed. Kaplan-Meier survival (log-rank) and Cox regression analysis were compared between the LKPDI quartiles. P < .05 was considered statistically significant. ResultsIn total, 821 transplants were included (mean age 31.7 ± 10.5 years, 62.5% male, n = 513). Mean follow-up was 64.7 ± 46.2 months. Mean estimated survival (Kaplan-Meier) was 128.9 ± 3 months (95% confidence interval [CI], 123-134). Ten-year death-censored graft survival was 61.4%. Median LKPDI was –2%, and mean LKDPI was –2.6% ± 14.6% (range, –50% to 42%). Pearson coefficient correlation between the LKDPI and death-censored graft survival was 0.024 (P = .4). Area under the curve (receiver operating characteristic [ROC]) for the LKDPI and death-censored graft loss was 0.54 (95% CI, 0.505-0.591) (P = .04). Recipients with the lowest LKDPI had lower risk of death-censored graft loss than other quartiles (P = .014 log-rank). Cox regression analysis was significant for the lower LKDPI quartile (<20%) (Exp B = 0.35; 95% CI, 0.14-0.9; P = .03). ConclusionThe LKDPI applies with moderate discrimination predictive power in our population. The best LKDPI patient has better death-censored graft survival. Further studies might continue to validate the LKDPI in other cohorts.

The prognosis of kidney transplant recipients with aorto-iliac calcification: a systematic review and meta-analysis.

SummaryThe prognosis of kidney transplant recipients (KTR) with vascular calcification (VC) in the aorto‐iliac arteries is unclear. We performed a systematic review and meta‐analysis to investigate their survival outcomes. Studies from January 1st, 2000 until March 5th, 2019 were included. Outcomes for meta‐analysis were patient survival, (death‐censored) graft survival and delayed graft function (DGF). Twenty‐one studies were identified, eight provided data for meta‐analysis. KTR with VC had a significantly increased mortality risk [1‐year: risk ratio (RR) 2.19 (1.39–3.44), 5‐year: RR 2.28 (1.86–2.79)]. The risk of 1‐year graft loss was three times higher in recipients with VC [RR 3.15 (1.30–7.64)]. The risk of graft loss censored for death [1‐year: RR 2.26 (0.58–2.73), 3‐year: RR 2.19 (0.49–9.82)] and the risk of DGF (RR 1.24, 95% CI 0.98–1.58) were not statistically different. The quality of the evidence was rated as very low. To conclude, the presence of VC was associated with an increased mortality risk and risk of graft loss. In this small sample size, no statistical significant association between VC and DGF or risk of death‐censored graft loss could be demonstrated. For interpretation of the outcomes, the quality and sample size of the evidence should be taken into consideration.

Clinic Nonattendance Is a Risk Factor for Poor Kidney Transplant Outcomes.

BackgroundThe aim of this study was to analyze the impact of clinic nonattendance within the first year after kidney transplantation on graft-related outcomes.MethodsOur retrospective analysis included all patients receiving their transplant (2007-2017) and receiving their long-term follow up at our center. Clinic nonattendance was extracted from electronic patient records and informatics systems, with highest clinic nonattenders stratified at the 75th percentile.ResultsData were analyzed for 916 kidney allograft recipients, with median follow up 1168 days (interquartile range, 455-2073 days). Median number of missed transplant clinic visits in the first year was 5 (interquartile range, 3-7) and nonattenders were defined above the 75th percentile. Nonattenders versus attenders were more likely to be black, ABO-incompatible, repeat kidney transplant recipients but less likely to have pretransplantation diabetes. Nonattenders versus attenders had longer hospital stays after their transplant surgery in days (14.4 vs 12.2 respectively, P = 0.007), higher rate of delayed graft function (21.3% vs 12.8% respectively, P = 0.005), higher risk for 1-year rejection (12.5% vs 7.8% respectively, P = 0.044), worse 1-year estimated glomerular filtration rate in mL/min (47.0 vs 54.1, respectively, P = 0.002) and increased risk for death-censored graft loss by median follow (17.5% vs 12.0%, respectively, P = 0.013). In a Cox regression model, kidney transplant recipients defined as clinic nonattenders within the first postoperative year demonstrated a significantly increased rate of death-censored graft loss (hazard ratio, 1.983; 95% confidence interval, 1.061-3.707; P = 0.032).ConclusionsKidney transplant recipients in the top quartile for nonattendance require additional support and supervision to help attenuate long-term risks to their graft function and survival.

Ethnicity matching and outcomes after kidney transplantation in the United Kingdom.

BackgroundKidneys from non-white donors have inferior outcomes, but it is unclear if ethnicity matching between donors and recipients achieves better post kidney transplant outcomes.MethodsWe undertook a retrospective, population cohort study utilising UK Transplant Registry data. The cohort comprised adult, kidney-alone, transplant recipients receiving their first kidney transplant between 2003–2015, with data censored at 1st October 2016. We included 27,970 recipients stratified into white (n = 23,215), black (n = 1,679) and south Asian (n = 3,076) ethnicity, with median post-transplant follow-up of 1,676 days (IQR 716–2,869 days). Unadjusted and adjusted Cox regression survival analyses were performed to investigate ethnicity effect on risk for graft loss and mortality.ResultsIn unadjusted analyses, matched ethnicity between donors-recipients resulted in better outcomes for delayed graft function, one-year creatinine, graft and patient survival but these differed by ethnicity matches. Compared to white-to-white transplants, risk for death-censored graft loss was higher in black-to-black and similar among Asian-to-Asian transplants, but mortality risk was lower for both black-to-black and Asian-to-Asian transplants. In Cox regression models, compared to white donors, we observed higher risk for graft loss with both south Asian (HR 1.38, 95%CI 1.12–1.70, p = 0.003) and black (HR 1.66, 95%CI 1.30–2.11, p<0.001) donated kidneys independent of recipient ethnicity. We observed no mortality difference with south Asian donated kidneys but increased mortality with black donated kidneys (HR 1.68, 95%CI 1.21–2.35, p = 0.002). Matching ethnicities made no significant difference in any Cox regression model. Similar results were observed after stratifying our analysis by living and deceased-donor kidney transplantation.ConclusionsOur data confirm inferior outcomes associated with non-white kidney donors for kidney transplant recipients of any ethnicity in a risk-adjusted model for the United Kingdom population. However, contrary to non-renal transplant literature, we did not identify any survival benefits associated with donor-recipient ethnicity matching.

Landscape of ABO-Incompatible Live Donor Kidney Transplantation in the US

Widespread implementation of ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) has been proposed as a means to partially ameliorate the national shortage of deceased donor kidneys. Acceptance of this practice has been encouraged by reports from experienced centers demonstrating acute rejection (AR) rates similar to those obtained with ABO-compatible (ABOc) LDKT. Acute rejection rate and graft survival after ABOi LDKT on a national level have yet to be fully determined. We studied adult (>18 years) LDKT recipients, from 2000 to 2015, reported to the Scientific Registry of Transplant Recipients. Acute rejection rates in the first post-transplant year (modified Poisson regression) and graft survival (Cox proportional hazards) were assessed by ABO compatibility status (ABOi: 930; ABOc: 89,713). Patients undergoing ABOi LDKT had an AR rate of 19.4% compared with 10.5% for ABOc recipients (p < 0.0001). After adjusting for recipient- and donor-related risk factors, patients undergoing ABOi LDKT were found to have a 1.76-fold greater risk for AR within 1 year of transplantation compared with ABOc LDKT recipients (adjusted relative risk [aRR] 1.76; 95% CI 1.54 to 2.01). Moreover, there was a 2.34-fold greater risk of death-censored graft loss at 1-year post-transplant among ABOi vs ABOc LDKT recipients (adjusted hazard ratio [aHR] 2.34; 95% CI 1.85 to 2.96). Based on these findings, the low rates of AR and excellent short-term graft survival presented in single center series may not be sustainable on a national level. These findings highlight the potential utility for identification of centers of excellence and regionalization of ABOi LDKT.

Pre-existing diabetes is a risk factor for increased rates of cellular rejection after kidney transplantation: an observational cohort study.

To investigate whether people with diabetes have an elevated risk of kidney allograft rejection in a well characterized clinical cohort in the setting of contemporary immunosuppression. We conducted a retrospective cohort study including all kidney allograft recipients at a single centre between 2007 and 2015, linking clinical, biochemical and histopathological data from electronic patient records. Data were analysed for 1140 kidney transplant recipients. The median follow-up was 4.4 years post-transplantation, and 117 of the kidney transplant recipients (10.2%) had diabetes at time of transplantation. Kidney allograft recipients with vs without diabetes were older (53 vs 45 years; P<0.001) and more likely to be non-white (41.0% vs 26.4%; P=0.001). Kidney allograft recipients with vs without diabetes had a higher risk of cellular rejection (19.7% vs 12.4%; P=0.024), but not of antibody-mediated rejection (3.4% vs 3.7%; P=0.564). Graft function and risk of death-censored graft loss were similar in the two groups, but kidney allograft recipients with diabetes had a higher risk of death and overall graft loss than those without diabetes. In a Cox regression model of non-modifiable risk factors at time of transplantation, diabetes was found to be an independent risk factor for cellular rejection (hazard ratio 1.445, 95% CI 1.023-1.945; P=0.042). Kidney allograft recipients with diabetes at transplantation should be counselled regarding their increased risk of cellular rejection but reassured regarding the lack of any adverse impact on short-to-medium term allograft function or survival.

Donor-Recipient Weight and Sex Mismatch and the Risk of Graft Loss in Renal Transplantation.

Relatively smaller kidney donor to recipient size is proposed to result in higher graft loss due to nephron underdosing and hyperfiltration injury, but the potentially additive effect of sex and weight mismatch has not been explored in detail. The purpose of this study was to determine if concurrent donor and recipient absolute weight and sex mismatch was associated with graft loss in a cohort of deceased donor kidney transplant recipients. The association of kidney donor and recipient absolute weight and sex difference with death-censored graft loss was explored using a cohort of United States deceased donor recipients between 2000 and 2014 through the Scientific Registry of Transplants Recipients. Donor-recipient sex pairings (male donor-male recipient; female donor-female recipient; male donor-female recipient; female donor-male recipient) were further stratified by donor and recipient absolute weight difference (>30 or 10-30 kg [donor<recipient; donor>recipient] or <10 kg [donor=recipient]) resulting in 20 weight and sex pairings. Time to death-censored graft loss for each pairing was evaluated using multivariable Cox proportional hazards models adjusting for donor, immunologic, surgical, and recipient predictors of graft loss compared with the reference group of male donor-male recipients with no weight mismatch (<10 kg difference). Of 115,124 kidney transplant recipients, 21,261 developed death-censored graft failure (median graft survival time was 3.8 years; quartile 1 to 3, 0.0 to 14.8 years). After multivariable adjustment, the highest relative hazards for graft failure were observed for female recipients of male donor kidneys and male recipients of female donor kidneys in situations where the recipient was >30 kg larger than donor (hazard ratio, 1.50; 95% confidence interval, 1.32 to 1.70; hazard ratio, 1.35; 95% confidence interval, 1.25 to 1.45, respectively). A concurrent mismatch in donor-recipient weight (donor<recipient) and donor-recipient sex is associated with a higher risk of death-censored graft loss in kidney transplantation.

Dementia and Alzheimer's Disease among Older Kidney Transplant Recipients.

Older patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked to Medicare claims through the US Renal Data System. We estimated dementia and AD risk (cumulative incidence) and studied factors associated with these sequelae using competing risks models. We estimated the risk of death-censored graft loss and mortality after developing dementia or the AD subtype of dementia, separately, using adjusted Cox proportional hazards models. Older recipients had a 10-year dementia risk ranging from 5.1% for recipients aged 55-60 years to 17.0% for recipients aged ≥75 years; 10-year AD risk ranged from 1.0% to 6.7%, respectively. The strongest predictors for dementia and AD were older recipient age and pretransplant diabetes. The 10-year graft loss risk was 28.8% for those who did not develop dementia and 43.1% for those who did, and the corresponding mortality risks were 55.7% and 89.9%, respectively. Older recipients with dementia had a 1.52-fold (95% confidence interval, 1.39 to 1.68) increased risk of graft loss and a 2.38-fold (95% confidence interval, 2.26 to 2.49) increased risk of mortality. We observed similar results for AD. We conclude that older KT recipients have a high risk of post-KT dementia and AD, and these sequelae associate with a profound effect on patient and graft survival.