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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.

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.

Worsening renal function in chronic kidney disease correlates with worsening right ventricular (RV) systolic function. We evaluated the association between kidney transplantation (KT) and RV structure and systolic function, and the relationships between RV and left ventricular (LV) changes, blood pressure, and specific cardiac biomarkers, in patients with end-stage kidney disease using cardiac magnetic resonance imaging (CMR). In this prospective, multi-centre, cohort study, 39 adult patients on dialysis receiving KT and 42 patients eligible for, but not yet receiving KT, were recruited. CMR was performed at baseline, and repeated at 12 months. Among 81 patients (mean age 51 years, 30% female), RV end-diastolic volume index (RVEDVi), end-systolic volume index (RVESVi), mass index (RVMi), and ejection fraction (RVEF) did not change significantly within either the dialysis or KT group over 12 months (all p ≥ 0.10). There were no significant differences in the 12-month changes of these parameters between the dialysis and KT groups (all p ≥ 0.10). RVMI demonstrated positive correlations with NT-proBNP and systolic blood pressure, but not GDF-15, at baseline and at 12 months. Changes in RVEDVi, RVESVi, and RVEF were positively correlated with changes in LVEDVi, LVESVi, and LVEF, respectively over 12 months (Spearman r = 0.72, 0.52, and 0.41; all p

BACKGROUND: Antibody-mediated rejection (AMR) accounts for >50% of kidney allograft loss. Donor-specific antibodies (DSA) against HLA and non-HLA antigens in the glomeruli and the tubulointerstitium cause AMR while inflammatory cytokines such as TNFα trigger graft injury. The mechanisms governing cell-specific injury in AMR remain unclear. METHODS: Unbiased proteomic analysis of laser-captured and microdissected glomeruli and tubulointerstitium was performed on 30 for-cause kidney biopsy specimens with early AMR, acute cellular rejection (ACR), or acute tubular necrosis (ATN). RESULTS: A total of 107 of 2026 glomerular and 112 of 2399 tubulointerstitial proteins was significantly differentially expressed in AMR versus ACR; 112 of 2026 glomerular and 181 of 2399 tubulointerstitial proteins were significantly dysregulated in AMR versus ATN (P

Supervised machine learning (ML) is a class of algorithms that "learn" from existing input-output pairs, which is gaining popularity in pattern recognition for classification and prediction problems. In this scoping review, we examined the use of supervised ML algorithms for the prediction of long-term allograft survival in kidney transplant recipients. Data sources included PubMed, the Cumulative Index to Nursing and Allied Health Literature, and the Institute for Electrical and Electronics Engineers (IEEE) Xplore libraries from inception to November 2019. We screened titles and abstracts and potentially eligible full-text reports to select studies and subsequently abstracted the data. Eleven studies were identified. Decision trees were the most commonly used method (n = 8), followed by artificial neural networks (ANN) (n = 4) and Bayesian belief networks (n = 2). The area under receiver operating curve (AUC) was the most common measure of discrimination (n = 7), followed by sensitivity (n = 5) and specificity (n = 4). Model calibration examining the reliability in risk prediction was performed using either the Pearson r or the Hosmer-Lemeshow test in four studies. One study showed that logistic regression had comparable performance to ANN, while another study demonstrated that ANN performed better in terms of sensitivity, specificity, and accuracy, as compared with a Cox proportional hazards model. We synthesized the evidence related to the comparison of ML techniques with traditional statistical approaches for prediction of long-term allograft survival in patients with a kidney transplant. The methodological and reporting quality of included studies was poor. Our study also demonstrated mixed results in terms of the predictive potential of the models.

Background Obesity is a significant public health concern; however, the incidence post solid-organ transplantation is not well reported. Methods This study determined the incidence and risk factors of obesity among pediatric solid-organ transplant recipients (heart, lung, liver, kidney, multiorgan) at The Hospital for Sick Children (2002-2011), excluding prevalent obesity. Follow-up occurred from transplantation until development of obesity, last follow-up, or end of study. Incidence of obesity was determined overall, by baseline body mass index, and organ group. Risk factors were assessed using Cox proportional-hazards regression. Results Among 410 (55% male) children, median transplant age was 8.9 (interquartile range [IQR]: 1.0-14.5) years. Median follow-up time was 3.6 (IQR: 1.5-6.4) years. Incidence of obesity was 65.2 (95% confidence interval [CI]: 52.7-80.4) per 1000 person-years. Overweight recipients had a higher incidence, 190.4 (95% CI: 114.8-315.8) per 1000 person-years, than nonoverweight recipients, 56.1 (95% CI: 44.3-71.1). Cumulative incidence of obesity 5-years posttransplant was 24.1%. Kidney relative to heart recipients had the highest risk (3.13 adjusted hazard ratio [aHR]; 95% CI: 1.53-6.40) for obesity. Lung and liver recipients had similar rates to heart recipients. Those with higher baseline body mass index (z-score; 1.72 aHR; 95% CI: 1.39-2.14), overweight status (2.63 HR; 95% CI: 1.71-4.04), and younger transplant age (y; 1.18 aHR; 95% CI: 1.12-1.25) were at highest risk of obesity. Higher cumulative steroid dosage (per 10 mg/kg) was associated with increased risk of obesity after adjustment. Conclusions Among all transplanted children at The Hospital for Sick Children, 25% developed obesity within 5-years posttransplant. Kidney recipients, younger children, those overweight at transplant, and those with higher cumulative steroid use (per 10 mg/kg) were at greatest risk. Early screening and intervention for obesity are important preventative strategies.

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.

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% CI 0.48-0.92). 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.

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.

Background Patients with AKI may require interhospital transfer to receive RRT. Interhospital transfer may lead to delays in therapy, resulting in poor patient outcomes. There is minimal data comparing outcomes among patients undergoing transfer for RRT versus those who receive RRT at the hospital to which they first present. Methods We conducted a population-based cohort study of all adult patients (≥19 years) who received acute dialysis within 14 days of admission to an acute-care hospital between April 1, 2004 and March 31, 2015. The transferred group included all patients who presented to a hospital without a dialysis program and underwent interhospital transfer (with the start of dialysis ≤3 days of transfer and within 14 days of initial admission). All other patients were considered nontransferred. The primary outcome was time to 90-day all-cause mortality, adjusting for demographics, comorbidities, and measures of acute illness severity. We also assessed chronic dialysis dependence as a secondary outcome, using the Fine and Gray proportional hazards model to account for the competing risks of death. In a secondary post hoc analysis, we assessed these outcomes in a propensity score–matched cohort, matching on age, sex, and prior CKD status. Results We identified 27,270 individuals initiating acute RRT within 14 days of a hospital admission, of whom 2113 underwent interhospital transfer. Interhospital transfer was associated with lower rate of mortality (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.84 to 0.97). Chronic dialysis dependence was not significantly different between groups (aHR, 0.98; 95% CI, 0.91 to 1.06). In the propensity score–matched analysis, interhospital transfer remained associated with a lower risk of death (HR, 0.88; 95% CI, 0.80 to 0.96). Conclusions Interhospital transfer for receipt of RRT does not confer higher mortality or worse kidney outcomes.

Inferring causality from observational studies can be challenging because of the perennial threat of biases from selection, measurement, and confounding. The gold standard study design in clinical research is the randomized controlled trial, because random allocation to treatment ensures that, on average, comparison groups are balanced with respect to both known and unknown prognostic factors. However, most clinically relevant exposure-outcome relationships are not amendable (logistically or ethically) to randomization. Thus, there has been an emergence of analytical approaches over the last several years to improve the validity of inferences made from observational studies. This review presents such an approach, instrumental variable analysis, a technique that has been used by economists for many years but has only recently seen increasing use in the health care literature. This review provides a description of the method, the assumptions underlying it, and recent applications in nephrology outcomes research. A more detailed review of the underlying mathematics, properties of an instrumental variable, and suggested elements for reporting an instrumental variable analysis are provided in the Supplementary Appendix.

In Ontario, kidney transplants have risen by 4% annually in recent years. An understanding of how this will affect the future annual number of posttransplant follow-up visits informs how to organize and deliver care.We projected the required number of annual posttransplant follow-up nephrology visits to inform posttransplant care delivery.Population-based retrospective cohort study.Linked databases from Ontario, Canada (population 14 million).Incident kidney transplant recipients from years 2008 to 2013.Frequency, distance traveled, and current and projected visits for posttransplant follow-up.Assuming a graft survival of 13 years and using the mean number of posttransplant clinic visits in years 1, 2, and 3, we forecasted the number of clinic visits needed in the year 2027.Using data from 2443 recipients, the mean (SD) number of clinic visits per recipient was 14.0 (9.2) in the first year after transplant, and 3.9 (6.2) and 3.0 (5.3) in the second and third year, respectively. If transplant rates rise by 4% per year until 2027, the estimated annual visits number will increase from 30 622 to 43 948. The median (25th, 75th percentile) distance between transplant center and patient's home was 30 (13, 65) km. The median round-trip travel distance for these visits in the first year after transplantation was 603 km per recipient, and median driving cost was Can$344 (2017).Regarding patient expense, limitations include that distances traveled were calculated orthodromically, and we did not account for patient cost of follow-up beyond that of vehicular travel. Regarding follow-up projections, limitations include the assumption that graft life span will not change, follow-up patterns do not differ between donor kidney type, and we did not survey stakeholders as to their preferred method of follow-up.We quantified the increase in posttransplant visits when regional annual rates of transplantation rise. Strategies recognizing the burden of these visits may enhance patient-centered care, as it is unclear how some patients manage costs, nor how the current health care system will manage the demand.Au cours des dernières années, le nombre de transplantations rénales a augmenté de 4 % annuellement en Ontario. Comprendre l’impact qu’aura cette augmentation sur le nombre annuel de visites de suivi post-transplantation dans les années à venir permettra d’organiser et de prodiguer les soins aux patients.Prévoir le nombre de visites de suivi post-transplantation qui seront requises dans le futur, de façon à orienter la prestation des soins.Étude de cohorte rétrospective basée sur une population.Les bases de données couplées de l’Ontario, au Canada (population: 14 millions).Les receveurs d’une greffe rénale entre 2008 et 2013.La fréquence des visites post-transplantation, la distance à parcourir pour s’y rendre, de même que leur nombre actuel et projeté.Nous avons estimé le nombre de visites cliniques qui seront nécessaires en 2027 à partir d’une survie du greffon estimée à 13 ans et du nombre moyen de visites pour les années 1, 2 et 3 post-transplantation.À partir des données de 2 443 receveurs, nous avons établi le nombre moyen (ET) de visites cliniques par receveur à 14,0 (9,2) pour la première année post-transplantation, à 3,9 (6,2) pour l’an 2 et à 3,0 (5,3) pour l’an 3. Si le nombre de greffes poursuit sa croissance au rythme de 4 % par an jusqu’en 2027, on estime que le nombre annuel de visites passera de 30 622 à 43 948. La distance médiane (25Les distances parcourues par les patients n’ont été calculées que de manière orthodromique et seules les dépenses liées aux déplacements en voiture ont été employées pour calculer les coûts aux patients. Les prévisions pour 2027 sont établies en tenant compte d’une survie du greffon qui demeurera stable, d’un schéma de suivi qui ne différera pas selon le type de donneur et du fait que nous n’avons pas questionné les intervenants quant à leur méthode de suivi préférée.Nous avons quantifié la hausse du nombre de visites post-transplantation en fonction de l’augmentation des taux de greffes annuels régionaux. Des stratégies reconnaissant le fardeau imposé par ces visites ont le potentiel d’améliorer les soins axés sur les patients puisqu’on ignore comment certains patients gèrent les coûts associés et comment le système de santé gèrera la demande.

The effect of living donor kidney allograft size on recipient outcomes is not well understood. In this study, we sought to investigate the relationship between preoperatively measured donor kidney volume and recipient estimated glomerular filtration rate (eGFR) in living donor kidney transplantation (LDKT). We studied computed tomography (CT) donor kidney volumes and recipient outcomes for 438 LDKTs at the Toronto General Hospital between 2007 and 2016. Estimated glomerular filtration rate (eGFR) was calculated at 1, 3, and 6 months and a multivariable linear regression model was fitted to study the effect of donor kidney volume on recipient eGFR. The mean volume and weight of the donated kidneys were 157.3 (± 32.3) cc and 186.7 (± 48.7) g, respectively. Kidney volume was significantly associated with eGFR on multivariable analysis (P

Background Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment. Methods We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007–2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence. Results We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014. Conclusion Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population.

Objective The association between pre-transplant mental health concerns and non-adherence and post-transplant outcomes after kidney transplantation is not fully established. We examined the relationship between a pre-transplant history of mental health concerns and non-adherence and post-transplant outcomes among kidney transplant recipients. Methods In this retrospective single center cohort study of adult kidney transplant recipients (n = 955) the associations between the history of mental health concerns or non-adherence and the time from kidney transplant to biopsy proven acute rejection; death-censored graft failure and total graft failure were examined using Cox proportional hazards models. Results Mean (SD) age was 51 (13) years, 61% were male and 27% had a history of diabetes. Twenty-two and 11% of patients had mental health concerns and non-adherence, respectively. Fifteen percent of the patients had acute rejection, 5.6% had death-censored graft failure and 13.0% had total graft failure. The history of mental health concerns was not associated with acute rejection, death-censored graft failure or total graft failure. Patients with versus without a history of non-adherence tended to have higher cumulative incidence of acute rejection (23.3% [95% CI: 16.1, 33.2] vs. 13.6% [95% CI: 11.4, 16.2]) and death-censored graft failure (15.0% [95% CI: 6.9, 30.8] vs. 6.4% [95% CI: 4.7, 8.7]) (log rank p = 0.052 and p = 0.086, respectively). These trends were not significant after multivariable adjustment. Conclusion In summary, a history of pre-transplant mental health concerns or non-adherence is not associated with adverse outcomes in patients who completed transplant workup and received a kidney transplant.

Background Active malignancies are a contraindication to transplantation, as immunosuppression can lead to worse cancer outcomes; therefore, ensuring transplant candidates are free of malignancy before transplantation is essential. This systematic review assesses the availability, quality, and consistency of recommended cancer evaluation prior to transplantation in Clinical Practice Guidelines (CPGs) for the selection of solid organ transplant candidates. Methods We systematically searched for CPGs for the assessment of transplant candidates. The characteristics of included CPGs, strength of recommendations and supporting evidence were extracted. A quality assessment of the CPGs was conducted using the AGREE II tool. Results We identified 52 CPG for the selection of solid organ transplant candidates. Only 13 (25%) included recommendations for cancer evaluation as part of the assessment of transplant candidates. Most recommended age and sex appropriate cancer screening as per the general population guidelines. Recommendations to evaluate for other malignancies and for high-risk candidates were variable. Most recommendations were based on expert opinion and only two CPGs provided an explicit link between the recommendations and supporting evidence. Conclusion There is a lack of clear and consistent recommendations for pretransplant cancer evaluation in existing CPGs. Although there is some consensus regarding the indication to screen for cancer as per the recommendations for the general population, these recommendations are not an appropriate risk reduction strategy for transplant candidates. Standardized protocols to ensure transplant candidates are cancer free prior to transplantation are needed.

Although initial therapy for cytomegalovirus (CMV) is usually successful, a significant subset of patients may have recurrent viremia. However, the epidemiology and risk factors for recurrence have not been fully defined, as well as the utility of prolonged antivirals after initial clearance.Solid organ transplant patients with first episode of CMV disease or asymptomatic viremia (≥1000 IU/mL) requiring treatment were identified by chart review. Clinical and virologic data were collected. The primary outcome was recurrence of CMV viremia or disease within 6 months of treatment discontinuation.The first episode of CMV viremia requiring antiviral therapy was assessed in 282 patients (147 CMV disease and 135 asymptomatic viremia). Cytomegalovirus occurred at 5.6 (0.63-27.7) months posttransplant. Recurrent CMV occurred in 30.5% patients at a median of 51 (0-160) days after discontinuation of therapy. Factors predictive of recurrence were treatment phase viral kinetics (P = 0.005), lung transplant (P = 0.002), CMV donor (D)+/recipient (R)- serostatus(P = 0.04) and recent acute rejection(P = 0.02). Prolonged antiviral therapy was given to 226 (80.1%) of 282 patients. Recurrence occurred in 73 (32.3%) of 226 patients that received prolonged antivirals versus 13 (23.2%) of 56 in those with no prolonged antivirals (P = 0.19).Recurrent CMV occurs in a significant percentage of patients after treatment of the first episode of CMV viremia/disease. CMV D+/R- serostatus, lung transplant, and treatment phase viral kinetics were significant predictors of recurrence. Continuation of prolonged antivirals beyond initial clearance was not associated with a reduced risk of recurrence.

Background: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described. Methods: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant. Results: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE. Conclusions: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss.

Nearly 80% of chronic renal failure patients have secondary hyperparathyroidism. Cinacalcet is used to lower parathyroid hormone; however, it is expensive and has side effects. When secondary hyperparathyroidism is resistant to medication or medications are inaccessible, parathyroidectomy is performed. Race and socioeconomic status influence access to care and surgical outcomes. We sought to evaluate the effect of race and socioeconomic status on parathyroidectomy rate as well as surgical outcomes of patients with secondary hyperparathyroidism. We undertook cross-sectional analysis of adults diagnosed with secondary hyperparathyroidism in the USA between 2012 and 2014, using the National Inpatient Sample. Univariate and multivariate analyses were used to determine associations between social disparities, likelihood to undergo parathyroidectomy, and surgical outcomes. Between 2012 and 2014, a national estimate of 724,170 hospitalizations were identified where patients had a diagnosis of secondary hyperparathyroidism. Operative rate was 0.67%. By socioeconomic status, differences in rates of surgery in the poorest compared to the richest were not significant (0.74% vs. 0.55%, OR 1.08, p = 0.5). African-American patients had higher rates of parathyroidectomy compared to Caucasians (1 vs. 0.74%, OR 1.49, p

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.

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.

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 m(2) to planned initiation of dialysis with an estimated GFR between 10 and 14 mL/min/1.73 m(2) (early start) or an estimated GFR between 5 and 7 mL/min/1.73 m(2) (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 m(2)), 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

Background Due to the increasing public acceptance of substance use, it is important to understand the association between substance use and access to kidney transplant and its outcomes. Here, we assess the sociodemographic predictors of substance use and the association between substance use and KT access. Methods Predictors of substance use were examined using a multivariable-adjusted multinomial logistic regression. The association between current substance use (tobacco and drug) and time from referral to listing or receipt of a KT was examined using Cox proportional hazards models. Results Of 2346 patients, the prevalence of current substance use was 17%. Predictors of current tobacco use were younger age, male sex, Caucasian ethnicity, being unemployed, and unmarried. Predictors of current drug use were younger age, male sex, Caucasian ethnicity, a history of non-adherence, and a history of mental health disorder. Patients with tobacco use had a decreased likelihood of being cleared for KT (hazard ratio [HR]:0.83[0.70, 0.99]) and receiving a KT (HR:0.80 [0.66, 0.96]). No association was seen in this sample for patients with drug use (HR:0.88 [0.69, 1.11] for being cleared for KT and 0.88 [0.69, 1.14] for KT, respectively). Conclusions Tobacco use was associated with a decreased likelihood of access to KT whereas there was no statistically significant difference in access to KT between patients with or without drug use.

IntroductionSubclinical inflammation is an important predictor of death-censored graft loss, and its treatment has been shown to improve graft outcomes. Urine CXCL10 outperforms standard post-transplant surveillance in observational studies, by detecting subclinical rejection and early clinical rejection before graft functional decline in kidney transplant recipients.Methods and analysisThis is a phase ii/iii multicentre, international randomised controlled parallel group trial to determine if the early treatment of rejection, as detected by urine CXCL10, will improve kidney allograft outcomes. Incident adult kidney transplant patients (n~420) will be enrolled to undergo routine urine CXCL10 monitoring postkidney transplant. Patients at high risk of rejection, defined as confirmed elevated urine CXCL10 level, will be randomised 1:1 stratified by centre (n=250). The intervention arm (n=125) will undergo a study biopsy to check for subclinical rejection and biopsy-proven rejection will be treated per protocol. The control arm (n=125) will undergo routine post-transplant monitoring. The primary outcome at 12 months is a composite of death-censored graft loss, clinical biopsy-proven acute rejection, de novo donor-specific antibody, inflammation in areas of interstitial fibrosis and tubular atrophy (Banff i-IFTA, chronic active T-cell mediated rejection) and subclinical tubulitis on 12-month surveillance biopsy. The secondary outcomes include decline of graft function, microvascular inflammation at 12 months, development of IFTA at 12 months, days from transplantation to clinical biopsy-proven rejection, albuminuria, EuroQol five-dimension five-level instrument, cost-effectiveness analysis of the urine CXCL10 monitoring strategy and the urine CXCL10 kinetics in response to rejection therapy.Ethics and disseminationThe study has been approved by the University of Manitoba Health Research Ethics Board (HS20861, B2017:076) and the local research ethics boards of participating centres. Recruitment commenced in March 2018 and results are expected to be published in 2023. De-identified data may be shared with other researchers according to international guidelines (International Committee of Medical Journal Editors [ICJME]).Trial registration numberNCT03206801; Pre-results.

Supplemental Digital Content is available in the text., Background. 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.

Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy-proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4-3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.

While renal transplantation is increasingly performed for end-stage renal disease, there is a paucity of data on cardiac screening and prognostication post-transplant. We determined the prognostic value of SPECT-MPI in a cohort who underwent renal transplantation. Among 4933 renal transplant recipients identified from the Canadian Organ Replacement Register, we examined outcomes of patients who underwent SPECT-MPI in Ontario, Canada. We determined morbidity and mortality using hospitalization and vital statistics registries, according to SPECT-MPI findings. We studied 282 renal transplant recipients (median age 46 years [25th, 75th percentile 37, 58]) with detailed SPECT-MPI results available, followed for a median of 5.7 (3.3, 7.7) years. Among those undergoing SPECT-MPI (66% pharmacologic stress), 41% had an abnormal summed stress score (SSS > 0) and 31% demonstrated abnormal summed difference score (SDS > 0). Rates of cardiovascular death were 0.4 per 100 person-years among those with normal stress perfusion (SSS = 0) and 0.4 per 100 person-years with SDS = 0. After adjusting for age, sex, prior myocardial infarction (MI), and cardiac risk factors, an SSS ≥ 4 conferred increased risk of cardiovascular death or cardiovascular hospitalization with adjusted hazard ratios of 2.52 (95% CI 1.41, 4.52, P = .002) for SSS 4-6 and 2.61 (95% CI 1.52, 4.49, P

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P

Delayed graft function (DGF), or post-operative acute kidney injury leading to the need for dialysis within the first week after kidney transplantation, most commonly occurs in the setting of donor kidney recovery and the ischemia–reperfusion injury associated with the transplantation process. Despite advances in immunosuppressive regimens and medical management of kidney transplant recipients, the short- and long-term sequelae of DGF continue to be important determinants of kidney allograft prognosis. In this review, we will highlight the following areas as it relates to DGF: definition, pathophysiology, epidemiology, graft and patient outcomes, prediction, and some points on management.

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.

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.

Cardiovascular mortality is the leading cause of death in ESRD. Whereas innate and adaptive immunity have established roles in cardiovascular disease, the role of humoral immunity is unknown. We conducted a retrospective cohort study in first-time adult kidney transplant candidates (N=161,308) using data from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services to evaluate whether anti-human leukocyte antigen antibodies, measured as panel reactive antibodies (PRAs), are related to mortality in ESRD. Relationships between time-varying PRAs and all-cause or cardiovascular mortality were assessed using Cox proportional hazards models. The analysis was repeated in subcohorts of candidates at lower risk for significant comorbidities, activated on the waiting list after 2007, or unsensitized at activation. Competing risks analyses were also conducted. Fully adjusted models showed increased hazard ratios (HRs [95% confidence intervals]) for all-cause mortality (HR, 1.02 [95% CI, 0.99 to 1.06]; HR, 1.11 [95% CI,1.07 to 1.16]; and HR,1.21 [95% CI,1.15 to 1.27]) and cardiovascular mortality (HR, 1.05 [95% CI,1.00 to 1.10]; HR,1.11 [95% CI,1.05 to 1.18]; and HR,1.21 [95% CI,1.12 to 1.31]) in PRA 1%-19%, PRA 20%-79%, and PRA 80%-100% categories compared with PRA 0%, respectively. Associations between PRA and the study outcomes were accentuated in competing risks models and in lower-risk patients and persisted in other subcohorts. Our findings suggest that PRA is an independent predictor of mortality in wait-listed kidney transplant candidates. The mechanisms by which PRA confers an incremental mortality risk in sensitized patients, and the role of transplantation in modifying this risk, warrant further study.

Transplantation is the preferred treatment for patients with kidney failure, but the need exceeds the supply of transplantable kidneys, and patients routinely wait >5 years on dialysis for a transplant. Coronary artery disease (CAD) is common in kidney failure and can exclude patients from transplantation or result in death before or after transplantation. Screening asymptomatic patients for CAD using noninvasive tests prior to wait-listing and at regular intervals (ie, annually) after wait-listing until transplantation is the established standard of care and is justified by the need to avoid adverse patient outcomes and loss of organs. Patients with abnormal screening tests undergo coronary angiography, and those with critical stenoses are revascularized. Screening is potentially harmful because patients may be excluded or delayed from transplantation, and complications after revascularization are more frequent in this population. CARSK will test the hypothesis that eliminating screening tests for occult CAD after wait-listing is not inferior to regular screening for the prevention of major adverse cardiac events defined as the composite of cardiovascular death, nonfatal myocardial infarction, urgent revascularization, and hospitalization for unstable angina. Secondary outcomes include the transplant rate, safety measures, and the cost-effectiveness of screening. Enrolment of 3,306 patients over 3 years is required, with patients followed for up to 5 years during wait-listing and for 1 year after transplantation. By validating or refuting the use of screening tests during wait-listing, CARSK will ensure judicious use of health resources and optimal patient outcomes.

Background Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function. Methods We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12 months after KT. Results Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p = 0.007) and global radial strain (GRS) (p = 0.003), but a decline in global longitudinal strain (GLS) over 12 months (p = 0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4 ± 6.4% at baseline, 60.6% ± 6.9% at 12 months; p = 0.001). For entire cohort, over 12 months, change in LVEF was significantly correlated with change in GCS (Spearman’s r = − 0.42, p 0.10). Conclusions Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12 months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings. Electronic supplementary material The online version of this article (10.1186/s12968-018-0504-5) contains supplementary material, which is available to authorized users.

Several different indices summarize patient comorbidity using health care data. An accurate index can be used to describe the risk profile of patients, and as an adjustment factor in analyses. How well these indices perform in persons with chronic kidney disease (CKD) is not well known.Assess the performance of 5 comorbidity indices at predicting mortality in 3 different patient groups with CKD: incident kidney transplant recipients, maintenance dialysis patients, and individuals with low estimated glomerular filtration rate (eGFR).Population-based retrospective cohort study.Ontario, Canada, between 2004 and 2014.Individuals at the time they first received a kidney transplant, received maintenance dialysis, or were confirmed to have an eGFR less than 45 mL/min per 1.73mFive comorbidity indices: Charlson comorbidity index, end-stage renal disease-modified Charlson comorbidity index, Johns Hopkins' Aggregated Diagnosis Groups score, Elixhauser score, and Wright-Khan index. Our primary outcome was 1-year all-cause mortality.Comorbidity indices were estimated using information in the prior 2 years. Each group was randomly divided 100 times into derivation and validation samples. Model discrimination was assessed using median c-statistics from logistic regression models, and calibration was evaluated graphically.We identified 4111 kidney transplant recipients, 23 897 individuals receiving maintenance dialysis, and 181 425 individuals with a low eGFR. Within 1 year, 108 (2.6%), 4179 (17.5%), and 17 898 (9.9%) in each group had died, respectively. In the validation sample, model discrimination was inadequate with median c-statistics less than 0.7 for all 5 comorbidity indices for all 3 groups. Calibration was also poor for all models.The study used administrative health care data so there is the potential for misclassification. Indices were modeled as continuous scores as opposed to indicators for individual conditions to limit overfitting.Existing comorbidity indices do not accurately predict 1-year mortality in patients with CKD. Current indices could be modified with additional risk factors to improve their performance in CKD, or a new index could be developed for this population.Il existe plusieurs indices cliniques qui résument les comorbidités des patients à partir des données du système de santé. Un indice fiable pourrait être utilisé pour décrire le profil de risque du patient et agir à titre de facteur correctif dans les analyses. Nous en savons encore peu sur la manière dont performent ces indices chez les personnes souffrant d’insuffisance rénale chronique (IRC).L’étude visait à évaluer la performance de cinq indices de comorbidité à prédire la mortalité dans trois différents groupes de patients : (1) des patients nouvellement greffés du rein; (2) les patients traités par dialyse d’entretien, et; (3) des individus présentant un faible débit de filtration glomérulaire estimé (DFGe).Il s’agit d’une étude de cohorte rétrospective représentative de la population étudiée.L’étude s’est tenue en Ontario, au Canada, entre 2004 et 2014.Les sujets ont été inclus au moment d’une première greffe rénale, alors qu’ils amorçaient un traitement de dialyse périodique ou au moment du diagnostic d’un DFGe inférieur à 45 ml/min/1,73 mCinq indices de comorbidité ont été évalués : l’indice de comorbidité de Charlson, une version de ce même indice ajustée pour l’insuffisance rénale terminale, leLes indices de comorbidité ont été estimés à partir des informations recueillies pour les deux ans précédant l’inclusion des sujets. Chaque groupe a été divisé 100 fois de façon aléatoire pour constituer des échantillons de dérivation et de validation. Le pouvoir discriminant du modèle a été évalué en utilisant la médiane de la statistique C des modèles de régression logistique, et la calibration a été estimée graphiquement.Nous avons répertorié un total de 4 111 receveurs d’une greffe rénale, de 23 897 individus suivant un traitement de dialyse périodique et de 181 425 individus dont le DFGe se situait sous le seuil des 45 ml/min/1,73 mNous avons employé les données administratives en santé et dès lors, certaines données ont pu être mal classées. Les indices évalués ont été modélisés sous forme de scores en continu plutôt que comme des indicateurs de l’état de santé individuel afin de limiter la surcorrection.Les indices de comorbidité existants n’ont pu prédire avec exactitude la mortalité sur une période d’un an dans une population de patients atteints d’insuffisance rénale chronique. Le pouvoir prédictif des indices actuels pourrait être amélioré dans les cas d’IRC par l’ajout de facteurs de risques supplémentaires. Sinon, l’élaboration d’un nouvel indice spécifique à cette population pourrait représenter une autre avenue.

Background Conflicting evidence exists regarding the relationship between socioeconomic status (SES) and outcomes after kidney transplantation. Methods We conducted a population-based cohort study in a publicly funded healthcare system using linked administrative healthcare databases from Ontario, Canada to assess the relationship between SES and total graft failure (ie, return to chronic dialysis, preemptive retransplantation, or death) in individuals who received their first kidney transplant between 2004 and 2014. Secondary outcomes included death-censored graft failure, death with a functioning graft, all-cause mortality, and all-cause hospitalization (post hoc outcome). Results Four thousand four hundred-fourteen kidney transplant recipients were included (median age, 53 years; 36.5% female), and the median (25th, 75th percentile) follow-up was 4.3 (2.1-7.1) years. In an unadjusted Cox proportional hazards model, each CAD $10000 increase in neighborhood median income was associated with an 8% decline in the rate of total graft failure (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.97). After adjusting for recipient, donor, and transplant characteristics, SES was not significantly associated with total or death-censored graft failure. However, each CAD $10000 increase in neighborhood median income remained associated with a decline in the rate of death with a functioning graft (adjusted (a)HR, 0.91; 95% CI, 0.83-0.98), all-cause mortality (aHR, 0.92; 95% CI, 0.86-0.99), and all-cause hospitalization (aHR, 0.95; 95% CI, 0.92-0.98). Conclusions In conclusion, in a universal healthcare system, SES may not adversely influence graft health, but SES gradients may negatively impact other kidney transplant outcomes and could be used to identify patients at increased risk of death or hospitalization.

Background Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients. Methods We conducted a population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto, from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death. Results A total of 951 recipients (kidney, n = 400; liver, n = 283; heart, n = 218; lung, n = 36; multiorgan/small bowel, n = 14) were compared with 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio, 32.9; 95% confidence interval [CI], 26.6-40.8). Risk was highest in the first year posttransplant (adjusted hazard ratio [aHR],176; 95% CI, 117-264), but remained elevated beyond 10 years (aHR, 10.8; 95% CI, 6.3-18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR, 93.1; 95% CI, 59.6-145.2). Conclusions Childhood transplant recipients have a 30 times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population.

Rationale & Objective 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. Study Design Population-based cohort study. Setting & Participants 33,500 incident maintenance dialysis patients in Ontario, Canada, and 532,452 incident patients with cancer (women: breast, colorectal, lung, or pancreas; men: prostate, colorectal, lung, or pancreas) from 1997 to 2015 using administrative health care databases. Exposure Incident kidney failure treated with maintenance dialysis versus incident diagnoses of cancer. Outcome All-cause mortality. Analytical Approach Kaplan-Meier product limit estimator was used to describe the survival of subgroups of study participants. Extended Cox regression with a Heaviside function was used to compare survival between patients with incident kidney failure treated with maintenance dialysis and individual diagnoses of various incident cancers. Results In men, dialysis had worse unadjusted 5-year survival (50.8%; 95% CI, 50.1%-51.6%) compared with prostate (83.3%; 95% CI, 83.1%-83.5%) and colorectal (56.1%; 95% CI, 55.7%-56.5%) cancer, but better survival than lung (14.0%; 95% CI, 13.7%-14.3%) and pancreas (9.1%; 95% CI, 8.5%-9.7%) cancer. In women, dialysis had worse unadjusted 5-year survival (49.8%; 95% CI, 48.9%-50.7%) compared with breast (82.1%; 95% CI, 81.9%-82.4%) and colorectal (56.8%; 95% CI, 56.3%-57.2%) cancer, but better survival than lung (19.7%; 95% CI, 19.4%-20.1%) and pancreas (9.4%; 95% CI, 8.9%-10.0%) cancer. After adjusting for clinical characteristics, similar results were found except when examining men and women with lung and pancreas cancer, for which dialysis patients had a higher rate of death 4 or more years after diagnosis. Women and men 70 years and older with incident kidney failure treated with maintenance dialysis had unadjusted 10-year survival probabilities that were comparable to pancreas and lung cancer. Limitations Cancer stage could be obtained for only a subpopulation. Conclusions Survival in incident dialysis patients was lower than in patients with several different solid-organ cancers. These results highlight the need to develop interventions to improve survival on dialysis therapy and can be used to aid advance care planning for elderly patients beginning treatment with maintenance dialysis.

Many patients with end-stage kidney disease (ESKD) do not appreciate how their survival may differ if treated with a kidney transplant compared with dialysis. A risk calculator (iChoose Kidney) developed and validated in the United States provides individualized mortality estimates for different treatment options (dialysis vs living or deceased donor kidney transplantation). The calculator can be used with patients and families to help patients make more educated treatment decisions.To validate the iChoose Kidney risk calculator in Ontario, Canada.External validation study.We used several linked administrative health care databases from Ontario, Canada.We included 22 520 maintenance dialysis patients and 4505 kidney transplant recipients. Patients entered the cohort between 2004 and 2014.Three-year all-cause mortality.We assessed model discrimination using the C-statistic. We assessed model calibration by comparing the observed versus predicted mortality risk and by using smoothed calibration plots. We used multivariable logistic regression modeling to recalibrate model intercepts using a correction factor, when appropriate.In our final version of the iChoose Kidney model, we included the following variables: age (18-80 years), sex (male, female), race (white, black, other), time on dialysis (6 months, 6-12 months,12 months), and patient comorbidities (hypertension, diabetes, and/or cardiovascular disease). Over the 3-year follow-up period, 33.3% of dialysis patients and 6.2% of kidney transplant recipients died. The discriminatory ability was moderate (C-statistic for dialysis: 0.70, 95% confidence interval [CI]: 0.69-0.70, and C-statistic for transplant: 0.72, 95% CI: 0.69-0.75). The 3-year observed and predicted mortality estimates were comparable and even more so after we recalibrated the intercepts in 2 of our models (dialysis and deceased donor kidney transplantation). As done in the United States, we developed a Canadian Web site and an iOS application called Dialysis vs. Kidney Transplant- Estimated Survival in Ontario.Missing data in our databases precluded the inclusion of all variables that were in the original iChoose Kidney (ie, patient ethnicity and low albumin). We were unable to perform all preplanned analyses due to the limited sample size.The original iChoose Kidney risk calculator was able to adequately predict mortality in this Canadian (Ontario) cohort of ESKD patients. After minor modifications, the predictive accuracy improved. The Dialysis vs. Kidney Transplant- Estimated Survival in Ontario risk calculator may be a valuable resource to help ESKD patients make an informed decision on pursuing kidney transplantation.Plusieurs patients atteints d’insuffisance rénale terminale (IRT) ignorent à quel point leurs chances de survie varient selon qu’ils sont traités par dialyse ou par une greffe rénale. Un modèle de prévision des risques (l’outil de calculValider l’outil de calculUne étude de validité externe.Plusieurs bases de données couplées du système de santé ontarien (Canada).Un total de 22 520 patients dialysés et de 4 505 receveurs d’une greffe de rein ont été inclus entre 2004 et 2014.La mortalité toutes causes sur une période de trois (3) ans.Nous avons évalué le pouvoir discriminant du modèle à l’aide de la statistique C. L’étalonnage du modèle a été établi en comparant les risques de mortalité observé et prédit, et à l’aide de courbes d’étalonnage lissées. Des modèles de régression logistique multivariés ont été employés pour réétalonner les valeurs à l’origine en utilisant au besoin un facteur de correction.Notre version définitive du modèle de prévision inclut les variables suivantes : l’âge du patient (18 à 80 ans), son genre, sa race (blanc, noir, autre), son expérience en dialyse (moins de 6 mois, entre 6 et 12 mois, plus de 12 mois) et ses comorbidités (hypertension, diabète et maladies cardiovasculaires). Au cours des trois ans de suivi, 33,3 % des patients dialysés et 6,2 % des receveurs d’une greffe sont décédés. Le pouvoir discriminant s’est avéré modéré avec une valeur de statistique C de 0,70 (IC 95 % : 0,69-0,70) pour la dialyse et de 0,72 (IC 95 % : 0,69-0,75) pour les greffes. Les taux de mortalité observé et estimé au cours des trois ans étaient comparables, et davantage après le réétalonnage des valeurs à l’origine dans deux de nos modèles (dialyse et receveur d’un rein d’un donneur décédé). Comme aux États-Unis, nous avons développé un site Web et une application iOS canadiens nommésDes informations manquantes dans les bases de données consultées nous ont empêchés de tenir compte de toutes les variables incluses dans le modèleLa version originale du modèle de prévision des risques

Background Kidney transplant recipients (KTR) may be at increased risk for Clostridium difficile infections (CDI) but risk factors and outcomes in this population have not been well studied. Methods An observational cohort study was conducted to determine the incidence, risk factors, and outcomes of CDI in KTR. A total of 1816 KTR transplanted between 2000 and 2013 at the Toronto General Hospital were included. Sixty-eight patients developed CDI. Controls were selected at a 4:1 ratio using risk-set sampling, and risk factors were explored using conditional logistic regression models. The impact of CDI on graft outcomes was evaluated using Cox proportional hazards models. Results The incidence rate of CDI was 0.64 cases/100 person-years. Independent predictors of CDI included antibiotic use (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.35-6.15), increased duration of hospitalization posttransplant (OR, 1.04; 95% CI, 1.02-1.06]), receiving a deceased donor kidney (OR, 2.98; 95% CI, 1.47-6.05), and a history of biopsy-proven acute rejection (OR, 5.82; 95% CI, 2.22-15.26). In the Cox proportional hazards model, CDI was found to be an independent risk factor for the subsequent development of biopsy-proven acute rejection (hazard ratio, 2.18; 95% CI, 1.34-3.55). Conclusions Our results confirm that transplant-specific factors place KTR at a higher risk for CDI. Clostridium difficile infections may increase the risk of adverse outcomes, such as biopsy-proven acute rejection. These findings emphasize the importance of preventive strategies to reduce the morbidity associated with CDI in KTR.

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.

BACKGROUND Early hospital readmission (EHR) is associated with morbidity, mortality, and significant healthcare costs. However, trends over time in EHR events in kidney transplant recipients have not been examined. We conducted a population-based cohort study using linked healthcare databases from Ontario, Canada, to determine whether the EHR incidence has changed from 2002 to 2014 in kidney transplant recipients. METHODS We defined EHR as an unplanned admission for any reason to an acute care hospital within 30 days of being discharged from the hospital for transplantation; admissions for elective procedures were excluded. RESULTS We included 5437 kidney transplant recipients. More recently transplanted recipients (2011 to 2014 vs 2002 to 2004) were older and more likely to have coronary artery disease. A total of 1128 (20.7%) kidney transplant recipients experienced an EHR. There was no trend in EHR across eras with a 30-day cumulative incidence of 23.0%, 21.4%, 18.4%, and 21.0% (P for trend =0.197) for the years 2002 to 2004, 2005 to 2007, 2008 to 2010, and 2011 to 2014, respectively. In the multivariable Cox proportional hazards model, we found no association between era of transplant and EHR. When examining variation in EHR across the 6 adult transplant centers, we found the 30-day cumulative incidence varied significantly from 15.5% to 27.1% (P < 0.001). CONCLUSIONS One in 5 kidney transplant recipients will experience an EHR; however, an increase in EHR over time has not been observed despite increasing recipient age and comorbidities.

Background: Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center ­European study involving 91 kidney transplant recipients (KTRs). Methods: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. Results: The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05–5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06–3.77). Conclusions: Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.

The "weekend effect" has been widely studied in various health care settings, but it has received less attention in the field of transplantation. The study by Mohan et al. reveals that this phenomenon exists in discard rates for deceased donor kidneys in the United States. These findings emphasize the importance of reducing unexplained variations in kidney discard rates, especially in light of the ongoing shortage of transplantable organs.

Supplemental digital content is available in the text., Background Prolonged warm ischemia time (WIT) is associated with graft failure and mortality, however less is known about factors associated with prolonged WIT. Methods In a cohort of United States deceased donor kidney transplant recipients identified using the Scientific Registry of Transplant Recipients (Jan 2005-Dec 2013), we identified factors associated with prolonged WIT (defined as ≥ 30 minutes versus 10-30 minutes) using hierarchical multilevel models adjusting for center effect, and WIT as a continuous variable using multiple linear regression of log-transformed data. Results Among 55 829 patients, potentially modifiable risk factors associated with prolonged WIT included increased recipient body mass index (BMI) (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.44-1.72 for BMI > 35), right donor kidney (OR, 1.14; 95% CI, 1.08-1.19), and a prolonged cold ischemic time (OR, 1.23; 95% CI, 1.13-1.33 for cold ischemia time > 24 hours). Transplanting a right kidney into an obese recipient further prolonged WIT (OR, 1.75; 95% CI, 1.55-1.98; for BMI > 35), increasing overall WIT by 11.0%. There was no correlation between median WIT for a given center and annual center transplant rate (pairwise correlation coefficient, 0.0898). Conclusions In conclusion, several modifiable factors are associated with prolonged WIT and may represent strategies to improve WIT and subsequent posttransplant outcomes.

Background There is a worldwide shortage of organs available for transplant, leading to preventable mortality associated with end-stage organ disease. While most citizens in many countries with an intent-to-donate “opt-in” system support organ donation, registration rates remain low. In Canada, most Canadians support organ donation but less than 25% in most provinces have registered their desire to donate their organs when they die. The family physician office is a promising yet underused setting in which to promote organ donor registration and address known barriers and enablers to registering for deceased organ and tissue donation. We developed a protocol to evaluate an intervention to promote registration for organ and tissue donation in family physician waiting rooms. Methods/design This protocol describes a planned, stepped-wedge, cluster randomized registry trial in six family physician offices in Ontario, Canada to evaluate the effectiveness of reception staff providing patients with a pamphlet that addresses barriers and enablers to registration including a description of how to register for organ donation. An Internet-enabled tablet will also be provided in waiting rooms so that interested patients can register while waiting for their appointments. Family physicians and reception staff will be provided with training and/or materials to support any conversations about organ donation with their patients. Following a 2-week control period, the six offices will cross sequentially into the intervention arm in randomized sequence at 2-week intervals until all offices deliver the intervention. The primary outcome will be the proportion of patients visiting the office who are registered organ donors 7 days following their office visit. We will evaluate this outcome using routinely collected registry data from provincial administrative databases. A post-trial qualitative evaluation process will assess the experiences of reception staff and family physicians with the intervention and the stepped-wedge trial design. Discussion Promoting registration for organ donation in family physician offices is a potentially useful strategy for increasing registration for organ donation. Increased registration may ultimately help to increase the number of organs available for transplant. The results of this trial will provide important preliminary data on the effectiveness of using family physician offices to promote registration for organ donation. Trial registration ClinicalTrials.gov, ID: NCT03213171. Registered on 11 July 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2333-5) contains supplementary material, which is available to authorized users.

The objective of this study was to evaluate systemic immunosuppression regimens used for patients undergoing ocular surface stem cell transplantation, including their benefits and adverse effects in the adjunctive management of limbal stem cell deficiency (LSCD). A systematic literature review was conducted using the MEDLINE and EMBASE databases (1980-2015). Data were collected on surgical intervention(s), type of immunosuppressive agent(s), duration of immunosuppression, percentage with stable ocular surface at last follow-up, mean follow-up time, and demographics. Data were also collected on adverse ocular and systemic outcomes. Sixteen reports met the inclusion criteria. There were no randomized controlled studies. Three studies were noncomparative prospective case series, whereas the majority were retrospective case series. Bilateral severe LSCD was the most common disease (50%), and keratolimbal allograft was the most common intervention (80%). Immunosuppressive regimens showed a progression from early studies using oral cyclosporine to later studies using combinations of mycophenolate mofetil and tacrolimus. Most studies included a course of high-dose systemic corticosteroids. For patients adherent to long-term systemic immunosuppression, stable ocular surface rates of 70%-80% at last follow-up were reported. Adverse effects included hypertension, diabetes mellitus, and biochemical abnormalities managed with pharmacotherapy or discontinuation of offending agents. There were no cases of mortality related to immunosuppression. However, the current literature does not elucidate which immunosuppressive regimen is most efficacious for different categories of LSCD or graft types. Evidence-based guidelines for systemic immunosuppression in limbal allograft therapy would benefit from randomized controlled and/or additional prospective studies. Long-term immunosuppression would benefit from close collaboration between ophthalmologists and transplant specialists to individualize treatments.

A retrospective cohort study of neonates born extremely preterm with persistent patent ductus arteriosus after unsuccessful pharmacologic closure compared outcomes between 166 surgically ligated and 142 nonligated neonates. After adjustment for confounders, ligation was not associated with the composite outcome of death or neurodevelopmental impairment, neurodevelopmental impairment alone, chronic lung disease, or retinopathy of prematurity among survivors.