Selective Elimination and Rationalization of Cell-based Assays in Deceased Donor Kidney Transplant Crossmatching.

Background: While there is increasing reliance on a negative virtual crossmatch to proceed with deceased donor kidney transplantation, a flow cytometry crossmatch (FCXM) is still usually performed after the transplant has already occurred. Our center has eliminated pretransplant physical crossmatches for most patients, and since 2018, we have eliminated the systematic performance of posttransplant FCXMs. Methods: We studied all deceased donor kidney transplants in our program between June 1, 2018, and March 31, 2021, to evaluate the impact of eliminating retrospective FCXMs on resource utilization and graft outcomes (ie, the occurrence of antibody-mediated rejection [AMR] in the first 3-mo posttransplant). Results: A total of 358 kidney transplants occurred during the study period, and approximately 70% of these transplants proceeded without the performance of any FCXM. Incidence rates of AMR were low (9.63 per 1000 person-months), which compared favorably with the incidence rate of AMR during the 3-y period preceding the policy (4.82 per 1000 person-months, P = 0.21). Conclusions: Our results suggest that moving away from retrospective FCXM and relying exclusively on the virtual crossmatch is safe and efficient for kidney allocation.

Cannabis use is associated with reduced access to kidney transplantation and an increased risk of acute rejection post-transplant.

BACKGROUND: The association between cannabis use and access to waitlisting, transplantation, and post-transplant outcomes remains uncertain. METHODS: Patients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post-transplant outcomes was evaluated using Cox proportional hazards models. RESULTS: Among 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR] .82 [95% confidence interval (CI): .72, .94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR .92, [95% CI: .79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy-proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death-censored graft failure was similarly elevated (aHR 1.60 [95% CI: .95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI: .90, 1.96]), death with graft function (aHR 1.06 [95% CI: .59, 1.89]), or hospital readmission in the first-year post-transplant (aHR 1.26 [95% CI: .95, 1.68]). CONCLUSIONS: Cannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users.

Renal Dysfunction After Heart Transplant.

BACKGROUND: Moderate or severe renal dysfunction (MSRD) is a frequent complication after heart transplantation. Strategies to delay progression and improve outcomes, such as renoprotective medications and timely referral to nephrology, remain important in providing care to heart transplant recipients with MSRD. RESEARCH QUESTION: What are chronic renal dysfunction's prevalence, risk factors, and optimal clinical management strategies in heart transplant recipients? DESIGN: This single-center, cross-sectional study examined patients who received a heart transplant from January 1, 2000, to June 30, 2011, and followed until December 31, 2011. Moderate or severe renal dysfunction was defined as a glomerular filtration rate of <60 mL/min/1.73 m2. RESULTS: The prevalence of MSRD among 195 heart transplant recipients was 60%. Variables associated with MSRD were female sex (odds ratio [OR]: 4.82; 95% CI, 1.72-13.54), greater age (OR: 1.10 per year; 95% CI, 1.06-1.14), time since transplant (OR: 1.0004 per year; 95% CI, 1.0001-1.0007), and mTOR inhibitor use (OR: 2.89; 95% CI, 1.24-6.71). Tacrolimus use (OR: 0.19; 95% CI, 0.05-0.71) and cyclosporine use (OR: 0.21; 95% CI, 0.05-0.80) were associated with patients without MSRD. Among patients with MSRD, 19.6% were referred to a nephrologist. Median eGFR remained stable at approximately 60 mL/min/1.73 m2 for 3 years after the study. CONCLUSIONS: Our results suggest that female sex, older age at transplant, and time since transplant are associated with MSRD in heart transplant recipients. Tacrolimus and cyclosporine use seemed renoprotective, but lower usage and increased mTOR inhibitor use may more likely indicate existing treatment patterns for patients with MSRD.

Renal cell carcinoma in kidney transplant recipients: incidence, trends, clinical management & outcomes.

OBJECTIVE: To describe the incidence, characteristics, clinical management, and outcomes of renal cell carcinoma (RCC) among a large, single-centre cohort of kidney transplant recipients (KTR). METHODS: We conducted an observational cohort study looking at KTR transplanted between January 2000-December 2017 (n = 2443) with ≥ 1 year of follow-up. Simultaneous kidney/pancreas transplants were excluded. The Kaplan-Meier product-limit method was used to determine the incidence of RCC. Characteristics and management of RCC were examined using descriptive statistics. Risk factors and clinical outcomes were analyzed using Cox regression models. RESULTS: The incidence of RCC among our cohort was 0.32 per 100 person-years, 2.1% of all KTRs. Almost half (47.1%) of cases occurred within 4 years post-transplant. The majority of cases were T1a (86.3%), clear-cell (45.1%), and in the native kidney (80.4%). KTR diagnosed with RCC had a twofold higher incidence of other malignancies versus KTR without RCC. Overall mortality, but not cancer-specific mortality, at 2- and 5-years post-transplant was threefold higher among KTR with RCC than those without. CONCLUSIONS: Incidence of RCC among our KTR was slightly higher than the general population; majority of cases occur in the native kidneys and are low stage, low grade. Indolent histologic variants were more common than the general population. KTR with RCC had a higher incidence of other malignancies. Overall, but not cancer-specific, mortality was higher among KTRs diagnosed with RCC.

The epidemiology of early deep vein thrombosis in kidney transplant recipients.

BACKGROUND: Because kidney transplant recipients may be at increased risk for deep vein thrombosis (DVT) following transplantation, we investigated the incidence, risk factors, treatments and outcomes of early DVT among kidney transplant recipients. METHODS: An observational, single-centre cohort study was conducted among adult kidney transplant recipients from Jan. 1, 2005, to Dec. 31, 2016 with 1-year followup. Time to DVT was assessed using the Kaplan-Meier method. Cox proportional hazards and linear regression models were used to analyze risk factors for and outcomes of DVT. RESULTS: The cumulative incidence of DVT was 4.25% at 3 months after transplant. In multivariable analysis, the use of depleting induction agents (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.05-4.35]), white recipient race (HR 1.84. 95% CI 1.08-3.12), the use of kidneys from expanded criteria donors (HR 2.13, 95% CI 1.05-4.32) and lower recipient body mass index (HR 0.95, 95% CI 0.91-1.00) increased the risk for early DVT. Peritransplant DVT prophylaxis was not associated with early DVT. Early DVT was not associated with reduced graft function, death, graft failure or first hospital readmission. CONCLUSION: Risk factors for early DVT in our cohort of kidney transplant recipients included white recipient race, use of depleting agents, lower recipient body mass index and use of expanded criteria donors. As practice patterns of donor and recipient selection in kidney transplantation evolve, the results of this study may aid in perioperative risk assessments and decision-making about the use of DVT prophylaxis.

Older Age is Associated With Lower Utilization of Living Donor Kidney Transplant.

Introduction: Older adults (65 years or older) constitute a substantial and increasing proportion of patients with kidney failure, potentially needing kidney replacement therapy. Living donor kidney transplant (LDKT) offers superior outcomes for suitable patients of all ages. However, exploring LDKT and finding a living donor could be challenging for older adults. Here, we assessed the association between age and utilization of LDKT and assessed effect modification of key variables such as ethnicity and language. Methods: This is a retrospective cohort study of patients with kidney failure referred for kidney transplant (KT) assessment in Toronto between January 2006 and December 2013. The association between age and having a potential living donor identified was assessed using logistic regression and the association between age and the receipt of LDKT was assessed using Cox proportional hazards models. Results: Of the 1617 participants, 50% were middle-aged (45-64 years old), and 17% were ≥65 years old. In our final multivariable adjusted models, compared to young adults, middle-aged and older adults had lower odds of having a potential living donor identified (odds ratio [OR], 0.47; confidence interval [CI], [0.35-0.63]; OR, 0.30; CI, [0.20-0.43]; P < 0.001, for middle-aged and older adults, respectively), and were less likely to receive LDKT (hazard ratio [HR], 0.79; CI, [0.63-0.99]; P = 0.04; HR, 0.47; CI, [0.30-0.72]; P = 0.001, for middle-aged and older adults, respectively.). Conclusion: Age is an independent predictor of receiving LDKT. Considering that nearly 90% of patients with kidney failure in Canada are >45 years of age, these results point to important and potentially modifiable age-related barriers to LDKT.

Risk Factors for First and Recurrent Fractures among Kidney Transplant Recipients.

Introduction: Kidney transplantation is associated with increased risk of bone fracture. Current literature reports widely variable fracture burden and contains limited data on risk factors for recurrent fractures. Methods: The incidence of all and major osteoporotic fractures (hip, forearm, thoracolumbar, and proximal humerus) were assessed. The risk factors for first and recurrent fractures among 1285 Canadian kidney transplant recipients transplanted between January 1, 2004, and December 31, 2013 were also identified. Results: The 10-year cumulative incidence of all fractures and major osteoporotic fractures in this population was 27.1% (95% CI: 22.5, 32.4) and 17.8% (95% CI: 13.4, 23.5), respectively. On multivariable analysis, female sex (HR = 1.64 [95% CI: 1.20, 2.26]), history of fracture (HR = 1.54 [95% CI: 1.12, 2.11]), and pretransplant diabetes (HR = 1.85 [95% CI: 1.29, 2.65]) were recipient factors found to increase the risk for any first fracture posttransplant. These risk factors persist in analysis with the time origin 3-months posttransplant, where transplant age (HR = 1.01 [95% CI: 1.00, 1.03]) and increased time on pretransplant dialysis (HR = 1.06 [95% CI: 1.00, 1.12]) also emerge as risk factors for first fracture. On multivariable shared frailty model analysis, increased risk of recurrent fractures was associated with recipient female sex (HR = 1.74 [95% CI: 1.21, 2.51]) and history of diabetes (HR = 1.76 [95% CI: 1.17, 2.66]). Discussion: The results suggested that some risk factors for first fracture may not inform risk of recurrent fractures. As such, fracture risk should be assessed accordingly to optimize long-term care and implement preventive measures.

Tacrolimus Formulation, Exposure Variability, and Outcomes in Kidney Transplant Recipients.

INTRODUCTION: Few studies have compared within-patient variability measures of tacrolimus trough levels by formulation and assessed within-patient variability on outcomes of kidney transplant recipients. RESEARCH QUESTIONS: (1) To compare within-patient variability of trough levels when converting from twice-daily to once-daily tacrolimus using standard deviation, coefficient of variation, and intrapatient variability percent. (2) To use the 3 measures of variability to examine the relationship between tacrolimus once-daily within-patient variability and total graft failure (i.e., return to chronic dialysis, pre-emptive retransplant, death with graft function). DESIGN: In this observational cohort study, within-patient variability of trough levels pre- and post-conversion from twice-daily to once-daily tacrolimus were compared using Wilcoxon matched-pairs signed-rank test. Graft outcomes were analyzed using Kaplan-Meier curves and multivariable Cox proportional hazards models. RESULTS: In 463 patients, within-patient variability differences pre- and post-conversion of median standard deviation, coefficient of variation, and intrapatient variability percent were -0.16 (P = 0.09), -0.01 (P = 0.52), and -1.41 (P = 0.32), respectively. Post-conversion, every 1 unit increase in within-patient variability standard deviation and intrapatient variability percent and every 0.1 unit increase in the coefficient of variation was associated with an increased hazard ratio [1.19 (P = 0.004), 1.02 (P = 0.030), 1.13 (P = 0.001), respectively] of total graft failure. Post-conversion, within-patient variability above cohort medians using standard deviation and coefficient of variation had a significantly higher risk of total graft failure. DISCUSSION: Under a program-wide conversion, no significant difference was observed in within-patient variability post-conversion from twice-daily to once-daily tacrolimus using the three measures of variability. High within-patient variability was associated with adverse transplant outcomes post-conversion.

Outcomes of early hospital readmission after kidney transplantation: Perspectives from a Canadian transplant centre.

BACKGROUND: Early hospital readmissions (EHRs) after kidney transplantation range in incidence from 18%-47% and are important and substantial healthcare quality indicators. EHR can adversely impact clinical outcomes such as graft function and patient mortality as well as healthcare costs. EHRs have been extensively studied in American healthcare systems, but these associations have not been explored within a Canadian setting. Due to significant differences in the delivery of healthcare and patient outcomes, results from American studies cannot be readily applicable to Canadian populations. A better understanding of EHR can facilitate improved discharge planning and long-term outpatient management post kidney transplant. AIM: To explore the burden of EHR on kidney transplant recipients (KTRs) and the Canadian healthcare system in a large transplant centre. METHODS: This single centre cohort study included 1564 KTRs recruited from January 1, 2009 to December 31, 2017, with a 1-year follow-up. We defined EHR as hospitalizations within 30 d or 90 d of transplant discharge, excluding elective procedures. Multivariable Cox and linear regression models were used to examine EHR, late hospital readmissions (defined as hospitalizations within 31-365 d for 30-d EHR and within 91-365 d for 90-d EHR), and outcomes including graft function and patient mortality. RESULTS: In this study, 307 (22.4%) and 394 (29.6%) KTRs had 30-d and 90-d EHRs, respectively. Factors such as having previous cases of rejection, being transplanted in more recent years, having a longer duration of dialysis pretransplant, and having an expanded criteria donor were associated with EHR post-transplant. The cumulative probability of death censored graft failure, as well as total graft failure, was higher among the 90-d EHR group as compared to patients with no EHR. While multivariable models found no significant association between EHR and patient mortality, patients with EHR were at an increased risk of late hospital readmissions, poorer kidney function throughout the 1st year post-transplant, and higher hospital-based care costs within the 1st year of follow-up. CONCLUSION: EHRs are associated with suboptimal outcomes after kidney transplant and increased financial burden on the healthcare system. The results warrant the need for effective strategies to reduce post-transplant EHR.

Incidence, risk factors, outcomes, and clinical management of BK viremia in the modern era of kidney transplantation.

BK viremia is endemic among kidney transplant recipients (KTRs). Incidence, risk factors, outcomes, and clinical management of detectable versus high BK viremia have not been considered previously in KTR in the modern era. This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥103 copies/ml constituted high viremia. Among 1193 KTRs, the cumulative probability of developing detectable and high BK viremia within 2 years posttransplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), nondepleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 ml/min/1.72 m2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, antiproliferative dose reductions were the most common initial management. BK viremia remains a common early complication in a modern cohort of KTRs. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation.

Surgical site complications in kidney transplant recipients: incidence, risk factors and outcomes in the modern era.

BACKGROUND: Surgical site complications (SSCs) are an important source of morbidity after kidney transplantation. We assessed the incidence, risk factors, outcomes and economic impact of SSCs in a large, diverse population of kidney transplant recipients. METHODS: We conducted a single-centre, observational cohort study of adult (age ≥ 18 yr) patients who underwent kidney transplantation between Jan. 1, 2005, and Dec. 31, 2015, with a minimum of 1 year of follow-up. Cases of SSC, including infections and wound dehiscence, were determined from patient records. Inpatient and outpatient hospital costs were determined 6 and 12 months after transplantation. We used the Kaplan-Meier product-limit method to determine the cumulative probability of SSCs and other outcomes. We evaluated risk factors and clinical outcomes using Cox proportional hazard ratios. Linear regression models were used to study the effect of SSCs on graft function. RESULTS: The incidence rate of SSCs within 30 days after transplantation was 4.19 per 100 person-months. The cumulative probability of developing an SSC within 30 days after transplantation was 4.13% (95% confidence interval [CI] 3.23%-5.28%). Increased recipient body mass index (BMI) (hazard ratio [HR] 1.07, 95% CI 1.02-1.11), longer cold ischemic time (HR 1.05, 95% CI 1.01-1.09) and transplantation in 2010-2012 versus 2005-2009 (HR 2.20, 95% CI 1.19-4.04) were risk factors for SSC development. In multivariable stepwise Cox proportional hazard models, SSC was a significant risk factor for death-censored graft failure (HR 3.08, 95% CI 1.60-5.90) and total graft failure (HR 2.09, 95% CI 1.32-3.32). Cumulative median hospital costs were $2238.46 greater for patients with an SSC than for those without. CONCLUSION: Increased BMI, longer cold ischemic time and the 2010-2012 transplantation period predisposed to SSCs. The development of SSCs was associated with a higher risk of graft failure. Strategies to minimize SSCs may improve outcomes after kidney transplantation and reduce costs.

Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients.

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

Lymphoceles: impact on kidney transplant recipients, graft, and healthcare system.

INTRODUCTION: Following kidney transplantation, lymphoceles can impact patient and graft outcomes, while resulting in significant hospital resource utilization. We aimed to characterize the incidence, risk factors, outcomes, and clinical management of lymphoceles among kidney transplant recipients and review impact on health system utilization at a high-volume center. MATERIALS AND METHODS: We conducted a single-center, observational cohort study on adults transplanted between January 1, 2005 and December 31, 2017. Incidence, risk factors, and clinical outcomes were assessed using the Kaplan-Meier product-limit method, multivariable logistic regression model, and Cox proportional hazards model, respectively. RESULTS: Lymphoceles developed in 72 of 1881 patients (3.8%). Multivariate analysis demonstrated that a longer time on dialysis before transplant [HR 1.09 (95% CI: 1.02, 1.17)], laparoscopic donor nephrectomy [HR 2.31 (95% CI: 1.04, 5.12)], and depleting induction therapy [HR 0.39 (95% CI: 0.18, 0.87)] were significant risk factors for lymphocele development. Lymphoceles independently increased the likelihood of hospital readmission [HR 3.96 (95% CI: 2.99, 5.25)] but had no significant effect on the likelihood of graft failure or death with graft function. Of 72 cases, 44 received a radiological or surgical intervention. Fifteen of 44 lymphoceles required further intervention due to re-accumulation or complications. CONCLUSION: Patients with longer dialysis times, kidneys from laparoscopic donor nephrectomy, and depleting induction therapy were associated with an increased risk for developing symptomatic lymphoceles. Our center's treatment for symptomatic lymphoceles did not result in significant graft dysfunction, but significantly higher healthcare resource utilization was noted.

Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection.

Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR. METHODS: We analyzed non-HLA antibodies in sera from 80 kidney transplant patients with AMR, mixed rejection, acute cellular rejection (ACR), or acute tubular necrosis. IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pretransplant or at the time of diagnosis. RESULTS: Fifteen non-HLA antibodies were significantly increased (P < 0.05) in AMR and mixed rejection compared with ACR or acute tubular necrosis pretransplant, and 7 at diagnosis. AMR and mixed cases showed significantly increased pretransplant levels of IgG anti-Ro/Sjögren syndrome-antigen A (SS-A) and anti-major centromere autoantigen (CENP)-B, compared with ACR. Together with IgM anti-CENP-B and anti-La/SS-B, these antibodies were significantly increased in AMR/mixed rejection at diagnosis. Increased IgG anti-Ro/SS-A, IgG anti-CENP-B, and IgM anti-La/SS-B were associated with the presence of microvascular lesions and class-II donor-specific antibodies (P < 0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared with ACR were reproduced in an external cohort of 60 kidney transplant patients. CONCLUSIONS: This is the first study implicating autoantibodies anti-Ro/SS-A and anti-CENP-B in AMR. These antibodies may participate in the crosstalk between autoimmunity and alloimmunity in kidney AMR.

Cumulative Deficits Frailty Index Predicts Outcomes for Solid Organ Transplant Candidates.

Despite comprehensive multidisciplinary candidacy assessments to determine appropriateness for solid organ transplantation, limitations persist in identifying candidates at risk of adverse outcomes. Frailty measures may help inform candidacy evaluation. Our main objective was to create a solid organ transplant frailty index (FI), using the cumulative deficits model, from data routinely collected during candidacy assessments. Secondary objectives included creating a social vulnerability index (SVI) from assessment data and evaluating associations between the FI and assessment, waitlist, and posttransplant outcomes. METHODS: In this retrospective cohort study of solid organ transplant candidates from Toronto General Hospital, cumulative deficits FI and SVI were created from data collected during candidacy evaluations for consecutive kidney, heart, liver, and lung transplant candidates. Regression modeling measured associations between the FI and transplant listing, death or removal from the transplant waitlist, and survival after waitlist placement. RESULTS: For 794 patients, 40 variable FI and 10 variable SVI were created (258 lung, 222 kidney, 201 liver, and 113 heart transplant candidates). The FI correlated with assessment outcomes; patients with medical contraindications (mean FI 0.35 ± 0.10) had higher FI scores than those listed (0.29 ± 0.09), P < 0.001. For listed patients, adjusted for age, sex, transplant type, and SVI, higher FI was associated with an increased risk of death (pretransplant or posttransplant) or delisting (hazard ratio 1.03 per 0.01 FI score, 95% confidence interval, 1.01-1.05, P = 0.01). CONCLUSIONS: A cumulative deficits FI can be derived from routine organ transplant candidacy evaluations and may identify candidates at higher risk of adverse outcomes.

Vitamin D Levels and the Risk of Posttransplant Diabetes Mellitus After Kidney Transplantation.

INTRODUCTION: Given the burden of posttransplant diabetes mellitus and the high prevalence of low vitamin D levels in kidney transplant recipients, it is reasonable to consider vitamin D as a novel and potentially modifiable risk factor in this patient population. RESEARCH QUESTION: To determine the association between 25- hydroxyvitamin D (25(OH)D) level and posttransplant diabetes among kidney transplant recipients. Design: In a multi-center cohort study of 442 patients who received a kidney transplant between January 1, 2005 and December 31, 2010, serum samples within one-year before transplant were analyzed for 25(OH)D levels. The association between 25(OH)D and posttransplant diabetes were examined in Cox proportional hazard models. RESULTS: The median 25(OH)D level was 66 nmol/L. The cumulative probability of diabetes at 12-months by quartiles of 25(OH)D (< 42, 42 to 64.9, 65 to 94.9, and > 95 nmol/L) were 23.4%, 26.9%, 21.4%, and 15.6%, respectively. Compared to the highest 25(OH)D quartile, hazard ratios (95% CI) for the risk were 1.85 (1.03, 3.32), 2.01 (1.12, 3.60), 1.77 (0.96, 3.25) across the first to third quartiles, respectively. The associations were accentuated in a model restricted to patients on tacrolimus. When modeled as a continuous variable, 25(OH)D levels were significantly associated with a higher risk of diabetes (hazard ratio 1.06, 95% CI: 1.01, 1.13 per 10 nmol/L decrease). DISCUSSION: Serum 25(OH)D was an independent predictor of posttransplant diabetes in kidney transplant recipients. These results may inform the design of trials using vitamin D to reduce the risk in kidney transplant recipients.

Ureteral strictures post-kidney transplantation: Trends, impact on patient outcomes, and clinical management.

INTRODUCTION: Ureteral strictures post-kidney transplantation (KT) can be a significant morbidity to the patient, often requiring surgical intervention and impacting graft function. We sought to investigate the incidence, clinical management, and outcomes of ureteral strictures among kidney transplant recipients (KTRs) at a large, multiorgan transplant center. METHODS: We conducted a single-center cohort study looking at KTRs who had transplant surgery from January 1, 2005 to March 31, 2017 with at least one-year followup (n=1742). Any KTRs done outside of our center or simultaneous multiorgan transplants were excluded. The Kaplan-Meier product-limit method was used to determine the incidence of ureteral strictures. Risk factors for ureteric strictures and clinical outcomes among patients with vs. without ureteric strictures were analyzed using Cox proportional hazards models. RESULTS: The incidence of ureteral strictures was 1.31 (95% confidence interval [CI] 0.85, 2.01) per 100 person-years or a cumulative incidence of 1.2%. We did not find any donor or recipient demographic variables that were independently associated with an increased risk of ureteral stricture development. A large proportion was managed successfully with radiological intervention alone (47.6%). Ureteral strictures were associated with death-censored graft failure (hazard ratio [HR] 7.17, 95% CI 2.81, 18.30), total graft failure (HR 3.04, 95% CI 1.41, 6.59), and hospital re-admission (HR 2.52, 95% CI 1.58, 4.00). CONCLUSIONS: Although uncommon, ureteral strictures can significantly impact patient outcomes after KT. A better understanding of risk factors and clinical management will be important to ensure optimal graft outcomes.

Early postoperative acute myocardial infarction in kidney transplant recipients: A nested case-control study.

INTRODUCTION: The epidemiology of early acute myocardial infarctions after kidney transplantation has not been well characterized. This study sought to examine the incidence, risk factors, and clinical outcomes of early acute myocardial infarctions or EAMI in kidney transplant recipients. METHODS: A total of 1976 patients who underwent kidney transplantation at our center from Jan 1, 2000, to Sept 30, 2016, were included. A nested case-control design was used to study EAMI risk factors using a conditional logistic regression model. A Cox proportional hazards model was used to assess the association of EAMI with death-censored graft failure, death with graft function, and total graft failure. RESULTS: Seventy four patients had an EAMI within 3 months post-transplant. Based on univariable analyses, risk factors for EAMI included age and recipient history of diabetes mellitus or coronary artery disease. After adjustment, recipient history of coronary artery disease was the only independent predictor for EAMI (OR 3.76, p < .001). Patients who experienced EAMI were more likely to experience death-censored graft failure, death with graft function, and total graft failure. CONCLUSION: While the incidence of EAMI in kidney transplant recipients is relatively low, these data show that EAMI has profound long-term effects on morbidity and mortality.

What Are the Burden, Causes, and Costs of Early Hospital Readmissions After Kidney Transplantation?

INTRODUCTION: Kidney transplant recipients are at risk for complications resulting in early hospital readmission. This study sought to determine the incidences, risk factors, causes, and financial costs of early readmissions. DESIGN: This single-centre cohort study included 1461 kidney recipients from 1 Jul 2004 to 31 Dec 2012, with at least 1-year follow-up. Early readmission was defined as hospitalization within 30 or 90-days postdischarge from transplant admission. Associations between various parameters and 30 and 90-days posttransplant were determined using multivariable Cox proportional hazards models. The hospital-associated costs of were assessed. RESULTS: The rates of early readmission were 19.4% at 30 days and 26.8% at 90 days posttransplant. Mean cost per 30-day readmission was 11 606 CAD. Infectious complications were the most common reasons and resulted in the greatest cost burden. Factors associated with 30 and 90-days in multivariable models were recipient history of chronic lung disease (hazard ratio or HR 1.78 [95%CI: 1.14, 2.76] and HR 1.68 [1.14, 2.48], respectively), median time on dialysis (HR 1.07 [95% CI: 1.01, 1.13]and HR 1.06 [95% CI: 1.01, 1.11], respectively), being transplanted preemptively (HR 1.75 [95% CI: 1.07, 2.88] and HR 1.66 [95% CI: 1.07, 2.57], respectively), and having a transplant hospitalization lasting of and more than 11 days (HR 1.52 [95% CI: 1.01, 2.27] and HR 1.65 [95% CI: 1.16, 2.34], respectively). DISCUSSION: Early hospital readmission after transplantation was common and costly. Strategies to reduce the burden of early hospital readmissions are needed for all patients.

Engaging high school students about organ donation and transplantation: an evaluation of the High School Outreach Initiative (HSOI) program.

Adolescents can be influential in changing societal perceptions of organ donation and transplantation (ODT) but current studies on youth are limited. We sought to (1) assess the baseline knowledge in ODT among students in Toronto, Canada, and (2) evaluate the effectiveness of the High School Outreach Initiative (HSOI) program presentations in changing awareness and interest about ODT. Pre- and post-presentation surveys were administered to high school students about their knowledge of ODT, awareness of donor registration, importance of donation, intent to register, and willingness to talk to their families about donation. Descriptive statistics were used to characterize the students' baseline knowledge and interest. Wilcoxon and McNemar tests were used to analyze changes in perceptions before and after the presentation. A total of 449 HSOI presentations were delivered to 33,090 students at 102 high schools in the Greater Toronto Area between 2012 and 2019. Data from 3327 surveys completed by students before a presentation showed 46.5% were not knowledgeable about ODT. For the 2-year period between 2017 and 2019, 1224 matched pre- and post-presentation surveys were collected. The 49.8% of students who stated they were not knowledgeable about ODT prior to the presentation decreased to 3.8% after (p < 0.001). Those who were not willing to register decreased by half after the presentation (p < 0.001). The HSOI is an effective educational program in improving youth's attitudes and perceptions toward ODT. Further directions of the program include the expansion to other cities and the collection of demographic information of students.