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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.

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.

Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches. The concept of mechanical power has emerged as a comprehensive metric encompassing key ventilator parameters associated with the genesis of ventilator-induced lung injury, including volume, pressure, flow, resistance, and respiratory rate. While numerous animal and human studies have linked mechanical power and ventilator-induced lung injury, its practical implementation at the bedside is hindered by calculation challenges, lack of equation consensus, and the absence of an optimal threshold. To overcome the constraints of measuring static respiratory parameters, dynamic mechanical power is proposed for all patients, regardless of their ventilation mode. However, establishing a causal relationship is crucial for its potential implementation, and requires further research. The objective of this review is to explore the role of mechanical power in ventilator-induced lung injury, its association with patient outcomes, and the challenges and potential benefits of implementing a ventilation strategy based on mechanical power.

Peritransplant TNF blockade with infliximab should not be used in recipients of deceased-donor kidney transplants due to lack of efficacy and an increased incidence of BK virus infection, according to results of a randomized controlled clinical trial. Our results underscore the need for properly controlled and powered trials to avoid falsely accepting unproven therapeutics and reporting incorrect low adverse event rates derived from small, uncontrolled experiments.

To report outcomes of keratolimbal allograft (KLAL) compatible for both human leukocyte (HLA) and/or blood type using oral prednisone, mycophenolate, and tacrolimus, with basiliximab if panel reactive antibodies (PRA) are present. Intravenous immunoglobulin (IVIG) was used post-operatively if donor-specific anti-HLA antibodies (DSA) were present.

Background: The kidney is the most common transplanted organ, accounting for almost all living donor transplantations and most deceased donor organ transplantations. The organ shortage has caused policymakers in many nations to debate the merits of adopting presumed consent legislation as a way to increase donor organ donation from deceased donors. Objective: To compare characteristics and kidney transplantation rates for countries with presumed consent for deceased organ donation with countries with explicit consent. Design: A longitudinal study of international kidney transplantation from 1997 to 2007. Setting: 44 nations performing kidney transplantation. Patients: Recipients of deceased and living kidney donor transplants. Measurements: Rates of transplantation of kidneys from deceased and living donors. Results: National characteristics, such as population size, proportion of the population self-identified as Catholic, per capita gross domestic product, health expenditures, and physician density, varied widely for the 22 nations with presumed consent and the 22 nations with explicit consent. Deceased donor kidney transplantation rates were higher in nations with presumed consent (median, 22.6 transplantations per million population [pmp]; interquartile range [IQR], 9.3 to 33.8) versus nations with explicit consent (median, 13.9 transplantations pmp; IQR, 3.6 to 23.1). Living donor kidney transplantation rates were lower in nations with presumed consent (median, 2.4 transplantations prop; IQR, 1.7 to 4.3) versus nations with explicit consent (median, 5.9 transplantations pmp; IQR, 2.3 to 12.2). The findings were consistent when nations were classified according to per capita gross domestic product, health expenditures, and physician density. Limitation: As with any observational study, associations may not be causal. Conclusion: Nations with presumed consent have higher rates of deceased donor kidney transplantation than nations with explicit consent. Any nation deciding to adopt presumed consent should carefully consider and reduce any negative effect on rates of living donation. Primary Funding Source: Canadian Institutes of Health Research and Lawson Health Research Institute.

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Healthcare is constantly evolving and thus requires lifelong learning. Evidence-based learning has been shown to lead to better patient outcomes, yet many healthcare professionals report gaps in their research abilities. We sought to evaluate the efficacy of a professional development program in addressing identified gaps.

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An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors.

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.

Objectives: To examine the practice patterns and perceptions of primary care physicians in the management of chronic diseases in kidney recipients, assess care provided to recipients, and identify barriers to the optimal delivery of primary care to recipients.Methods: A self-administered questionnaire on the primary care of kidney recipients was developed and implemented. The survey investigated physician comfort and practice patterns in providing preventive and chronic care to recipients, patient self-management support, and physician perceptions on communication with transplant centers and barriers to ideal care.Results: A total of 210 physicians completed the survey (response rate of 22%). Among the respondents, 73% indicated they were currently providing care to kidney recipients. The majority of physicians specified that they rarely (57%) or never (20%) communicate with transplant centers. Most physicians felt comfortable providing care to recipients for non-transplant-related issues (92.5%), vaccinations (85%), and periodic health examinations (94%). The majority (75.3%) of physicians felt uncomfortable managing the immunosuppressive medications of recipients. Physicians’ most commonly stated barriers to delivering optimal care to recipients were insufficient guidelines provided by the transplant center (68.9%) and lack of knowledge in managing recipients (58.8%). Suggested resources by physicians to improve their comfort level in managing recipients included guidelines and continuing medical educational activities related to transplantation.Conclusions: Our results suggest that there are barriers to delivering optimal primary care to kidney recipients. The approach to providing resources needed to bridge the knowledge gap for physicians in the management of recipients requires further exploration.

IMPORTANCE: Keratinocyte carcinoma (KC), also known as nonmelanoma skin cancer, is the most common malignancy after solid organ transplant. Epidemiologic data on posttransplant KC in North America are limited by a lack of KC capture in cancer and transplant registries. OBJECTIVE: To estimate the incidence and identify risk factors for posttransplant KC. DESIGN, SETTING, AND PARTICIPANTS: This population-based inception cohort study in Ontario, Canada, used linked administrative databases and a health insurance claims–based algorithm. Participants were adult recipients of a first kidney, liver, heart, or lung transplant from January 1, 1994, to December 31, 2012. The cohort (n = 10 198) was followed up to December 31, 2013. Data were analyzed from May 31, 2016, to April 21, 2017. EXPOSURES: Solid organ transplant with functioning graft. MAIN OUTCOMES AND MEASURES: Age- and sex-adjusted standardized incidence ratio for KC in the transplant cohort was compared with that in the general population. Cumulative incidence of posttransplant KC was estimated using cumulative incidence functions, accounting for the competing risks of death or kidney graft loss. The association between KC and patient-, transplant-, and health services–related factors was evaluated with a multivariable cause-specific hazards model. RESULTS: A total of 10 198 transplant recipients were included in the study. The median (interquartile range [IQR]) age at transplant was 51 (41-59) years, with most recipients being male (6608 [64.8%]) and white (5964 [58.5%]). Posttransplant KC was diagnosed in 1690 patients (16.6%) after a median (IQR) of 3.96 (1.94-7.09) years, with an incidence rate of 2.63 per 100 patient-years (95% CI, 2.51-2.76). The rate of KC was significantly higher after transplant compared with the general population (standardized incidence ratio, 6.61; 95% CI, 6.31-6.93). The highest 10-year cumulative incidence was in the subsets of patients with a history of pretransplant skin cancer (66.5%), older than 50 years at transplant (27.5% for 51-65 years; 40.5% for >65 years), and of the white race (24.1%). The strongest independent risk factors for KC included older age at transplant (adjusted hazard ratio [aHR], 9.27; 95% CI, 7.08-12.14 for >65 years vs 18-35 years), white vs black race (aHR, 8.50; 95% CI, 4.03-17.91), pretransplant invasive skin cancer (aHR, 4.30; 95% CI, 3.72-4.98), and posttransplant precancerous skin lesions (aHR, 4.32; 95% CI, 3.77-4.95). CONCLUSIONS AND RELEVANCE: The incidence of KC appeared to be substantially increased after transplant, particularly in patients who were older at transplant, were white, and had a history of cancerous or precancerous skin tumors; intensified skin cancer screening, education, and early use of chemopreventive interventions may be warranted for these high-risk patient subsets.

Dialysis prior to kidney transplantation may have a detrimental effect on post-transplant outcomes. However, prior studies have not fully characterized the nature of this relationship and may have been subject to residual confounding. Here we investigated the association between pre-transplant dialysis duration and two post-transplant outcomes: all-cause death and death with functioning graft. This was a retrospective, population-based, cohort study in all deceased donor kidney transplants performed in Ontario, Canada, from April 1, 2002 to March 31, 2013. Patient blood type was chosen as an instrumental variable and a two-stage modeling procedure that included a threshold-adjusted Cox proportional hazards model was used to assess the association between dialysis time and the two post-transplant outcomes. Among 4,440 transplant recipients, the relative risk of all-cause death associated with each dialysis year prior to three years was 42% and fell to 5% per additional dialysis year thereafter. For death with functioning graft, each dialysis year before and after 2.8 years increased the relative risk by 31% and 4%, respectively. Peak panel reactive antibody of more than 50% was independently associated with an elevated risk of death with functioning graft but not with the risk of all-cause death. Thus, our findings highlight the urgency to develop strategies to ensure timely transplant listing and to shorten the total dialysis time before transplantation, with the goal of enhancing kidney transplant outcomes.

IMPORTANCE: Published in 2010, the Initiating Dialysis Early and Late (IDEAL) randomized clinical trial, which randomized patients with an estimated glomerular filtration rate (GFR) between 10 and 15 mL/min/1.73 m2 to planned initiation of dialysis with an estimated GFR between 10 and 14 mL/min/1.73 m2 (early start) or an estimated GFR between 5 and 7 mL/min/1.73 m2 (late start), concluded that early initiation was not associated with improved survival or clinical outcomes. OBJECTIVE: To assess the association between the IDEAL trial results and the proportion of early dialysis starts over time. DESIGN, SETTING, AND PARTICIPANTS: This interrupted time series analysis used data from the Canadian Organ Replacement Register to study adult (≥18 years of age) patients with incident chronic dialysis between January 1, 2006, and December 31, 2015, in Canada, which has a universal health care system. Patients from the province of Quebec were excluded because its privacy laws preclude submission of deidentified data without first-person consent. The patients included in the study (n = 28 468) had at least 90 days of nephrologist care before starting dialysis and a recorded estimated GFR at dialysis initiation. Data analyses were performed from November 2016 to January 2019. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of early dialysis starts (estimated GFR >10.5 mL/min/1.73 m2), and the secondary outcomes included the proportions of acute inpatient dialysis starts, patients who started dialysis using a home modality, and patients receiving hemodialysis who started with an arteriovenous access. Measures included the trend prior to the IDEAL trial publication, the change in this trend after publication, and the immediate consequence of publication. RESULTS: The final cohort comprised 28 468 patients, of whom 17 342 (60.9%) were male and the mean (SD) age was 64.8 (14.6) years. Before the IDEAL trial, a statistically significant increasing trend was observed in the monthly proportion of early dialysis starts (adjusted rate ratio, 1.002; 95% CI, 1.001-1.004; P = .004). After the IDEAL trial, an immediate decrease was observed in the proportion of early dialysis starts (rate ratio, 0.874; 95% CI, 0.818-0.933; P < .001), along with a statistically significant change in trend between the pretrial and posttrial periods (rate ratio, 0.994; 95% CI, 0.992-0.996; P < .001). No statistically significant differences were found in acute inpatient dialysis initiations, the proportion of patients receiving home dialysis as the initial modality, or the proportion of arteriovenous access creation at hemodialysis initiation after the IDEAL trial publication. CONCLUSIONS AND RELEVANCE: The publication of the IDEAL trial appeared to be associated with an immediate and meaningful change in the timing of dialysis initiation in Canada.

IMPORTANCE: Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. OBJECTIVE: To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. DESIGN, SETTING, AND PARTICIPANTS: We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. MAIN OUTCOMES AND MEASURES: Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. RESULTS: The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. CONCLUSIONS AND RELEVANCE: In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Background: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients.Design: This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes.Results: Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein–Barr virus (EBV) mismatched (D+/R−) transplants and 12 from EBV-positive recipients (R+). Recipients with D+/R− matches were at a significantly higher risk of developing PTLD than R+ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78).Discussion: Epstein–Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.

The mortality rate is high among dialysis patients, but how this compares with other diseases such as cancer is poorly understood. We compared the survival of maintenance dialysis patients with that for patients with common cancers to enhance the understanding of the burden of end-stage kidney disease.

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To determine whether low socioeconomic status (SES), with or without universal drug coverage, predicts end-stage renal disease (ESRD) and survival after dialysis in patients with diabetes.

Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems.

Solid organ transplant recipients have a high risk of keratinocyte carcinoma (non‐melanoma skin cancer). Consensus‐based transplant guidelines recommend annual dermatological examination but the impact on skin cancer–related outcomes is unclear. We conducted a population‐based, retrospective, inception cohort study using administrative health databases in Ontario, Canada to evaluate the association between adherence to annual dermatology assessments (time‐varying exposure) and keratinocyte carcinoma‐related morbidity and mortality after transplantation. The primary outcome was the time to first advanced (highly morbid or fatal) keratinocyte carcinoma. Among 10 183 adults receiving their first transplant from 1994 to 2012 and followed for a median of 5.44 years, 4.9% developed an advanced keratinocyte carcinoma after transplant. Adherence to annual dermatology assessments for at least 75% of the observation time after transplant was associated with a 34% reduction in keratinocyte carcinoma‐related morbidity or death compared with adherence levels below 75% (adjusted hazard ratio 0.66, 95% CI0.48‐0.92). Adherence levels were universally low (median proportion of time spent in adherence 0%, inter‐quartile range 0‐27%). Only 45% of transplant recipients had ever seen a dermatologist and 2.1% were fully adherent during the entire observation period. Strategies are needed to improve adherence rates in order to help decrease long‐term morbidity after transplant. In this population‐based, inception cohort study of transplant recipients, a higher level of adherence to annual dermatology assessment is associated with a significant 34% reduction in the rate of highly morbid or fatal keratinocyte carcinoma.

Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain.

The authors show that the incidence rate of clostridium difficile infection (CDI) in kidney transplant recipients is 0.64 cases/100 person-years. Risks include duration of antibiotics, deceased donor, and acute rejection for which CDI is an independent risk factor. Supplemental digital content is available in the text.

Using a propensity score matched cohort study design, the authors report on a worse survival of organ transplant recipients with pretransplant malignancy than without. However, the increased risk, both cancer specific or not, is mainly conveyed by high risk malignancies.

Context: Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood.Objective: To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation.Methods: In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models.Results: A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio [HR] 2.34 [95% confidence interval [CI], 1.37-4.00]) and high baseline body mass index (HR 1.05 [95% CI, 1.02-1.09]) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 [95% CI, 0.78-0.97]) was significantly associated with a decreased risk of leukopenia.Conclusions: These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.

In Ontario, Canada, the authors show that early hospital readmisssion (within 30 days postdischarge) in kidney transplant recipients has not changed over time between 2002 to 2014, despite a population of recipients becoming older with more prevalent coronary disease. Supplemental digital content is available in the text.

Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality.

This single-center retrospective cohort analysis suggests that patients with a history of mental health disorders or nonadherence have lower chance to completing the workup and/or undergoing kidney transplantation, opening opportunities for investigations of targeted psychosocial support interventions. Supplemental digital content is available in the text.

Recurrent CMV occurs in 30% of patients after treatment of the first episode of CMV viremia or disease, and CMV D+/R- serostatus, lung transplant, and slow resolution of viremia predict recurrence; whereas prolonged antiviral secondary prophylaxis does not associate with a reduced risk of recurrence.

IMPORTANCE: Observational studies have associated patent ductus arteriosus (PDA) ligation among preterm infants with adverse neonatal outcomes and neurodevelopmental impairment in early childhood, with a resultant secular trend away from surgical treatment. However, to our knowledge, studies have inadequately addressed sources of residual bias, including survival bias and major neonatal morbidities arising before exposure to ligation. OBJECTIVE: Evaluate the association between PDA ligation vs medical management and neonatal and neurodevelopmental outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of preterm infants younger than 28 weeks gestational age born between January 1, 2006, and December 31, 2012, with clinical and echocardiography diagnoses of hemodynamically significant PDA was conducted at 3 tertiary neonatal intensive care units and affiliated follow-up programs. EXPOSURE: Surgical ligation vs medical management. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18 to 24 months corrected age. Secondary outcomes included death before discharge, NDI, moderate-severe chronic lung disease, and severe retinopathy of prematurity. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. RESULTS: Of 754 infants with hemodynamically significant PDA (mean [standard deviation] gestational age 25.7 [1.2] weeks and birth weight 813 [183] grams), 184 (24%) underwent ligation. Infants who underwent ligation had a higher frequency of morbidities before PDA closure, including sepsis, necrotizing enterocolitis, and a dependence on mechanical ventilation. After adjusting for perinatal characteristics and preligation morbidities, there was no difference in the odds of death or NDI (adjusted odds ratio (aOR), 0.83; 95% CI, 0.52-1.32), NDI (aOR, 1.27; 95% CI, 0.78-2.06), chronic lung disease (aOR, 1.36; 95% CI, 0.78-2.39) or severe retinopathy of prematurity (aOR, 1.61; 95% CI, 0.85-3.06). Ligation was associated with lower odds of mortality (aOR, 0.09; 95% CI, 0.04-0.21). CONCLUSIONS AND RELEVANCE: Patent ductus arteriosus ligation among preterm neonates younger than 28 weeks gestational age was not associated with the composite outcome of death or NDI, and there were no differences in chronic lung disease, retinopathy of prematurity, or NDI among survivors. Mortality was lower among infants who underwent ligation, though residual survival bias could not be excluded. Previously reported associations of ligation with increased morbidity may be because of bias from confounding by indication.

Access to kidney transplantation (KT) is significantly reduced for all ethnic groups assessed compared to Caucasian Canadians, and this is primarily driven by differences in access to living donor KT. Further research is needed to identify the causes of inequities. Supplemental digital content is available in the text.

This systematic review demonstrates that a history of a pretransplant malignancy is associated with increased risk of all-cause mortality, cancer-specific mortality and of developing de novo cancer after transplantation, and that such a history should be considered carefully in the pretransplant evaluation process and posttransplant immunosuppression choices. Supplemental digital content is available in the text.

A Canadian retrospective registry study suggests that mortality or major cardiovascular event has remained stable over time despite the increase in age and number of comorbidities of kidney transplant recipients. Nevertheless, the reasons behind this observation are unclear. Supplemental digital content is available in the text.

The Canadian Society of Transplantation and Canadian Blood Services conducted a consensus forum on combined renal/nonrenal transplants, as they are not part of Canadian organ-specific allocation models at present. The purpose of this initiative was to make recommendations, develop eligibility criteria, and a decision-making model on listing and allocation. Forty-two participants with expertise in combined transplantation participated in the consensus forum. The United States and Canadian data were reviewed. The consensus forum made recommendations regarding the following: (1) investigation of etiology, severity, duration, and level of renal dysfunction; (2) documentation of degree of nonreversible kidney injury; (3) eligibility for combined (either simultaneous or staged) transplantation; (4) research. Key recommendations were: (1) patients with end-stage nonrenal disease with estimated glomerular filtration rate less than 30 mL/min per 1.73 m2for longer than 1 month or on dialysis less than 3 months, who fulfill criteria for nonreversibility of renal dysfunction (by level and duration of renal dysfunction, imaging, and pathology findings), would be eligible for combined renal/nonrenal transplantation; (2) patients on dialysis longer than 3 months would be eligible for combined renal/nonrenal transplantation; (3) staged renal after nonrenal transplantation with subsequent prioritized allocation of renal transplant was endorsed in selected cases. The validation and impact of these recommendations on allocation will require further studies.The authors report on the conclusions of a Canadian Consensus Forum devoted to renal/nonrenal transplantations with regard to eligibility, listing, and allocation. They produce useful recommendations about investigations of renal dysfunction, criteria of nonreversibiity of renal dysfunction, eligilibity for combined transplantation, and research.

Li and colleagues review the literature on hospital readmissions after organ transplantation. While many critical associations are documented, it remains to be defined which can be modified to improve outcomes.

IMPORTANCE: Solid-organ transplant recipients (SOTRs) are at greater risk of developing some cancers than the general population; however, because they are also at increased risk of mortality from noncancer causes, the effect of transplantation on cancer mortality is unclear. OBJECTIVE: To describe cancer mortality in SOTRs and to assess whether SOTRs are at increased risk of cancer mortality compared with the general population. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study of patients who underwent solid-organ transplantation in Ontario, Canada, between 1991 and 2010 with 85 557 person-years of follow-up through December 31, 2011. Solid-organ transplantation was identified using the national transplant register and linked to the provincial cancer registry and administrative databases. The analysis was conducted between November 2013 and February 2015. EXPOSURE: Solid-organ transplantation. MAIN OUTCOMES AND MEASURES: Cancer mortality for SOTRs was compared with that of the general population using standardized mortality ratios (SMRs). Mortality and cause of death were ascertained by record linkage between the Canadian Organ Replacement Register, the Ontario Cancer Registry, and the Office of the Registrar General of Ontario death database. RESULTS: A total of 11 061 SOTRs were identified, including 6516 kidney, 2606 liver, 929 heart, and 705 lung transplantations. Recipients had a median (interquartile range) age of 49 (37-58) years, and 4004 (36.2%) were women. Of 3068 deaths, 603 (20%) were cancer related. Cancer mortality in SOTRs was significantly elevated compared with the Ontario population (SMR, 2.84 [95% CI, 2.61-3.07]). The risk remained elevated when patients with pretransplant malignant neoplasms (n = 1124) were excluded (SMR, 1.93 [95% CI, 1.75-2.13]). The increased risk was observed irrespective of transplanted organ. The SMR for cancer death after solid-organ transplantation was higher in children (SMR, 84.61 [95% CI, 52.00-128.40]) and lower in patients older than 60 years (SMR, 1.88 [95% CI, 1.62-2.18]) but remained elevated compared with the general population at all ages. CONCLUSIONS AND RELEVANCE: Cancer death rate in SOTRs was increased compared with that expected in the general population; cancer was the second leading cause of death in these patients. Advances in prevention, clinical surveillance, and cancer treatment modalities for SOTRs are needed to reduce the burden of cancer mortality in this population.

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000–2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99–1.15), 1.13 (1.06–1.22), 1.17 (1.09–1.26), 1.20 (1.12–1.30), and 1.23 (1.15–1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.

Context: An increasing demand for kidney transplantation has enticed some patients with end-stage renal disease (ESRD) to venture outside their country of residence, but their posttransplant outcomes may be suboptimal.Objective: We compared the risks and clinical outcomes among tourists, or patients who pursue a kidney transplant abroad, versus patients who received a transplant at the Toronto General Hospital (TGH).Methods: A single-center, 1:3 matched (based on age at transplant, time on dialysis, and year of transplant) cohort study was conducted. Forty-five tourists were matched with 135 domestic transplant recipients between January 1, 2000, and December 31, 2011. Multivariable Cox proportional hazards models were fitted to assess graft and patient outcomes.Results: Among the 45 tourists, the majority (38 of 45) traveled to the Middle East or Far East Asia, and most received living donor kidney transplants (35 of 45). Multivariable Cox proportional hazards models showed that tourists had a higher risk for the composite outcome of acute rejection, death-censored graft failure, or death with graft function (DWGF; hazard ratio [HR] 2.08, 95% confidence interval [CI]: 1.06-4.07). Tourists also showed a higher risk for the individual end points of acute rejection, DWGF, and posttransplant hospitalizations.Conclusion: Patients going abroad for kidney transplantation may have inferior outcomes compared to domestic patients receiving kidney transplants. Patients who are contemplating an overseas transplant need to be aware of the increased risk of adverse posttransplant outcomes and should be appropriately counseled by transplant professionals during the pretransplant evaluation process.

Created by the US National Organ Transplant Act in 1984, the Scientific Registry of Transplant Recipients (SRTR) is obligated to publicly report data on transplant program and organ procurement organization performance in the United States. These reports include risk-adjusted assessments of graft and patient survival, and programs performing worse or better than expected are identified. The SRTR currently maintains 43 risk adjustment models for assessing posttransplant patient and graft survival and, in collaboration with the SRTR Technical Advisory Committee, has developed and implemented a new systematic process for model evaluation and revision. Patient cohorts for the risk adjustment models are identified, and single-organ and multiorgan transplants are defined, then each risk adjustment model is developed following a prespecified set of steps. Model performance is assessed, the model is refit to a more recent cohort before each evaluation cycle, and then it is applied to the evaluation cohort. The field of solid organ transplantation is unique in the breadth of the standardized data that are collected. These data allow for quality assessment across all transplant providers in the United States. A standardized process of risk model development using data from national registries may enhance the field.

Supplemental digital content is available in the text.

An analysis of 4821 kidney transplant recipients with median age of 50 years in the Ontario, Canada healthcare databases of kidney transplant patients transplanted between 1994–2009 shows that cumulative non-vertebral fracture rates are lower than previously reported. Supplemental digital content is available in the text.

In the general population, high serum uric acid concentration is a risk factor for gout. It is unknown whether donating a kidney increases a living donor’s risk of gout as serum uric acid concentration increases in donors after nephrectomy.