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The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD.Prospective cohort study.Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study.Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications.Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients.Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression.Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia.Unmeasured confounding factors.Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.

Background The impact of research findings on clinical practice usually remains uncertain and unmeasured. To address this problem, we examined the long-term clinical and economic impact of the Initiating Dialysis Early and Late (IDEAL) trial using data from the Australia and New Zealand Dialysis and Transplant Registry. Methods We performed a registry-based study including all incident adult dialysis patients in Australia and New Zealand from July 2000 to June 2018. A piecewise linear regression model was used to examine differences in mean estimated glomerular filtration rate (eGFR) at dialysis commencement for the years prior to (2000–2010) and following (2010–2018) publication of the IDEAL trial results. The return on investment (ROI) was calculated using the total cost of performing the IDEAL trial and the cost or savings accruing in Australia and New Zealand from changes in dialysis initiation practice. Results From July 2000 to June 2010, mean eGFR at dialysis commencement increased at a rate of 0.21 mL/min/1.73 m2/year [95% confidence interval (CI) 0.19–0.23]. After the IDEAL trial results were published, mean eGFR at dialysis commencement did not show any temporal change [−0.01 mL/min/1.73 m2/year (95% CI −0.03–0.01)]. The ROI of the IDEAL trial was AU$35.70/AU$1 spent, an estimated savings to the Australian and New Zealand health systems of up to AU$84 million/year. Conclusions The previous trend to higher eGFR at dialysis commencement changed following publication of the IDEAL trial results to a steady eGFR that has continued for a decade, avoiding unnecessary dialysis treatments and accruing savings to the Australian and New Zealand health systems.

Introduction People with chronic kidney disease (CKD) experience reduced quality of life (QoL) because of the high symptom and treatment burden. Limited data exist on the factors associated with overall and domain-specific QoL across all CKD stages. Methods Using data from a prospective, multinational study (Australia, New Zealand, Canada, and Spain) in 1696 participants with CKD, we measured overall and domain-specific QoL (pain, self-care, activity, mobility, anxiety/depression) using the EuroQoL, 5 dimension, 3 level. Multivariable linear regression and logistic modeling were used to determine factors associated with overall and domain-specific QoL. Results QoL for patients with CKD stages 3 to 5 (n = 787; mean, 0.81; SD, 0.20) was higher than in patients on dialysis (n = 415; mean, 0.76; SD, 0.24) but lower than in kidney transplant recipients (n = 494; mean, 0.84; SD, 0.21). Factors associated with reduced overall QoL (β [95% confidence intervals]) included being on dialysis (compared with CKD stages 3–5: –0.06 [–0.08 to –0.03]), female sex (–0.03 [–0.05 to –0.006]), lower educational attainment (– 0.04 [–0.06 to –0.02), lacking a partner (–0.04 [–0.06 to –0.02]), having diabetes (–0.05 [–0.07 to –0.02]), history of stroke (–0.09 [–0.13 to –0.05]), cardiovascular disease (–0.06 [–0.08 to –0.03]), and cancer (–0.03 [–0.06 to –0.009]). Pain (43%) and anxiety/depression (30%) were the most commonly affected domains, with dialysis patients reporting decrements in all 5 domains. Predictors for domain-specific QoL included being on dialysis, presence of comorbidities, lower education, female sex, and lack of a partner. Conclusions Being on dialysis, women with CKD, those with multiple comorbidities, lack of a partner, and lower educational attainment were associated with lower QoL across all stages of CKD., Graphical abstract

Background Non-invasive biomarkers may predict adverse events such as acute rejection after kidney transplantation and may be preferable to existing methods because of superior accuracy and convenience. It is uncertain how these biomarkers, often derived from a single study, perform across different cohorts of recipients. Methods Using a cross-validation framework that evaluates the performance of biomarkers, the aim of this study was to devise an integrated gene signature set that predicts acute rejection in kidney transplant recipients. Inclusion criteria were publicly available datasets of gene signatures that reported acute rejection episodes after kidney transplantation. We tested the predictive probability for acute rejection using gene signatures within individual datasets and validated the set using other datasets. Eight eligible studies of 1454 participants, with a total of 512 acute rejections episodes were included. Results All sets of gene signatures had good positive and negative predictive values (79-96%) for acute rejection within their own cohorts, but the predictability reduced to less than 50% when tested in other independent datasets. By integrating signatures sets with high specificity scores across all studies, a set of 150 genes (included CXCL6, CXCL11, OLFM4 and PSG9) which are known to be associated with immune responses, had reasonable predictive values (varied between 69-90%). Conclusions A set of gene signatures for acute rejection derived from a specific cohort of kidney transplant recipients do not appear to provide adequate prediction in an independent cohort of transplant recipients. However, integration of gene signatures sets with high specificity scores may improve the prediction performance of these markers.

This registry-based study evaluated the contribution of center characteristics to kidney transplant outcomes in adult first kidney transplant recipients in Australia and New Zealand between 2004 and 2014. Primary outcomes were mortality and graft failure, and secondary outcomes were transplant complications. Overall, 6970 transplants from 17 centers were included. For deceased donor transplants, 5-year patient and graft survival rates varied considerably (81.0-93.9% and 72.2-88.3%, respectively). Variations in mortality and graft failure were partially reduced after adjustment for patient characteristics (1% and 20% reductions) and more markedly reduced after adjustment for center characteristics (41% and 55% reductions). For living donor transplants, 5-year patient and graft survival rates varied (89.7-100% and 79.2-96.9%, respectively). Centers with high average total ischemic times (>14 h) were associated with higher mortality for both deceased (adjusted hazard ratio [(AHR] 2.24, 95% CI 1.21-4.13) and living donor transplants (AHR 1.76, 95% CI 1.02-3.04). Small center size (

Dual left turn lanes are typically operated with protected left turn signals, which means extra delay during non-peak hours compared to permissive operation. To reduce this delay, the authors designed, installed, and tested a “dynamic left turn intersection” (DLTi), which is a new way to operate dual left turn lanes. With DLTi, the both lanes are operated with protected phasing during the peak hours when higher capacity is needed, and only the leftmost left turn lane remains open for protected-permissive operation during off-peak hours. The test showed substantial delay savings, the crash experience has been minimal, and the public comments received have been predominantly negative but not overwhelming. Around 85 percent of left-turning motorists complied when the rightmost left turn lane was closed. The team believes that the DLTi test has been a success, and that agencies should begin searching for other suitable locations for DLTi installation.

Background The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. Material and methods This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. Results The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99–1.26), death-censored graft failure (HR 1.09, 95% CI 0.92–1.28), death (HR 1.15, 95% CI 0.98–1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91–1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92–2.68). Conclusion Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

For patients with type 1 diabetes mellitus who progress to the point of requiring renal replacement therapy, the relative benefits of simultaneous pancreas and kidney transplantation (SPK) and deceased donor kidney transplantation across different age categories compared to dialysis are uncertain. Using Australian and New Zealand registry data from 2006 to 2016, a probabilistic Markov model (n = 10 000) was built comparing patient survival between SPK and deceased donor kidney transplantation with dialysis. Compared to dialysis, the average life years saved (LYS) and quality-adjusted life years (QALY) for SPK and deceased donor kidney transplantation were 5.48 [95% CI 5.47, 5.49] LYS and 6.48 [6.47, 6.49] QALY, and 3.38 [3.36, 3.40] LYS and 2.46 [2.45, 2.47] QALY, respectively. For recipients aged 50 years or younger, receiving a deceased donor kidney, the average incremental gains compared to dialysis were 4.13 [4.10, 4.16] LYS and 2.99 [2.97, 3.01] QALY, and for recipients older than 50 years, 3.05 [3.02, 3.08] LYS and 2.25 [2.23, 2.27] QALY. Compared to dialysis, SPK transplantation incurs the greatest benefits in LYS and QALY for patients with type 1 diabetes requiring renal replacement therapy. Patients older than 50 years still experience survival benefits from deceased donor kidney transplantation compared to dialysis.

This paper provides a method for characterizing space events using the framework of conceptual spaces. We focus specifically on estimating and ranking the likelihood of collisions between space objects. The objective is to design an approach for anticipatory decision support for space operators who can take preventive actions on the basis of assessments of relative risk. To make this possible our approach draws on the fusion of both hard and soft data within a single decision support framework. Contextual data is also taken into account, for example data about space weather effects, by drawing on the Space Domain Ontologies, a large system of ontologies designed to support all aspects of space situational awareness. The framework is coupled with a mathematical programming scheme that frames a mathematically optimal approach for decision support, providing a quantitative basis for ranking potential for collision across multiple satellite pairs. The goal is to provide the broadest possible information foundation for critical assessments of collision likelihood.

Kinking of the kidney transplant vessels late after the operation is a rare complication that can lead to significant morbidity and mortality. We present a case of positional ischemia of the renal allograft resulting from dynamic and positional kinking of the graft vasculature, which was diagnosed by ultrasonography with the patient standing. The graft was repositioned into the sub-rectus pocket and the ischaemic injury resolved.

Aim Careful assessment of the potential donor-recipient relationship is recommended by guidelines to prevent undue coercion, and to ensure realistic expectations and genuine motivations. However, relationships are complex, nuanced and value-laden, and can be challenging to evaluate in living kidney donation. We aimed to describe the attitudes and approaches of transplant clinicians towards assessing the relationship between potential living kidney donors and their recipients. Methods Semi-structured interviews were conducted with 54 transplant clinicians (nephrologists, surgeons, coordinators, social workers, psychiatrists and psychologists) from 32 transplant centres across nine countries including Australia, United States, Canada and New Zealand. Transcripts were analyzed thematically. Results Four themes were identified: protecting against vulnerability and premature decisions (ensuring genuine motivation, uncovering precarious dynamics and pre-empting conflict, shared accountability, relying on specialty psychosocial expertise, trusting intimate bonds, tempering emotional impulsivity); safeguarding against coercion (discerning power imbalance, justified inquiry, awareness of impression management); minimizing potential threat to relationships (preserving the bond, giving equitable attention to donors and recipients, ensuring realistic expectations); and ambiguities in making judgments (adjudicating appropriateness and authenticity of relationships, questioning professional intervening, uncertainties in subjective and emotional assessments). Conclusions Clinicians felt ethically compelled to minimize the risk of undue coercion and to protect donors and recipients when evaluating the donor-recipient relationship. However, disentangling voluntariness and altruism from potential undisclosed pressures to enact societal and family duty, making decisions within this complex, multi-stakeholder context, and avoiding the imposition of undue paternalism and donor autonomy, were challenging. Multidisciplinary expertise and practical strategies for managing uncertainties are required.

To determine the incremental gains in graft and patient survival under a risk-based, deceased donor kidney allocation compared with the current Australian algorithm.Risk-based matching algorithms were applied to first graft, kidney only recipients (n = 7513) transplanted in Australia between 1994 and 2013. Probabilistic models were used to compare the waiting time, life, and QALYs and graft years between the 8 risk-based allocation strategies against current practice.Compared with current practice, Kidney Donor Risk Index-Estimated Posttransplant Survival matching of the lowest 20% of scores reduced median waiting time by 0.64 years (95% confidence interval [CI], 0.52-0.73) for recipients aged 30 years or younger, but increased waiting time by 0.94 years (95% CI, 0.79-1.09) for recipients older than 60 years. Among all age groups, the greatest gains occurred if Kidney Donor Risk Index-Estimated Posttransplant Survival matching of the lowest 30% of scores was used, incurring a median overall gain of 0.63 (95% CI, 0.03-1.25) life years and 0.78 (95% CI, 0.30-1.26) graft years compared with the current practice. A median gain in survival of 1.91 years for younger recipients (aged 30-45 years) was offset by a median reduction in survival (by 0.95 life years) among the older recipients. Prioritization of lower-quality donor kidneys for older candidates reduced the waiting time for recipients older than 45 years, but no changes in graft and patient survivals were observed.Risk-based matching engendered a moderate, overall increase in graft and patient survivals, accrued through benefits for recipients 45 years or younger but disadvantage to recipients older than 60 years.

Cancer is the second most common cause of mortality and morbidity in kidney transplant recipients after cardiovascular disease. Kidney transplant recipients have at least a twofold higher risk of developing or dying from cancer than the general population. The increased risk of de novo and recurrent cancer in transplant recipients is multifactorial and attributed to oncogenic viruses, immunosuppression and altered T cell immunity. Transplant candidates and potential donors should be screened for cancer as part of the assessment process. For potential recipients with a prior history of cancer, waiting periods of 2-5 years after remission - largely depending on the cancer type and stage of initial cancer diagnosis - are recommended. Post-transplantation cancer screening needs to be tailored to the individual patient, considering the cancer risk of the individual, comorbidities, overall prognosis and the screening preferences of the patient. In kidney transplant recipients diagnosed with cancer, treatment includes conventional approaches, such as radiotherapy and chemotherapy, together with consideration of altering immunosuppression. As the benefits of transplantation compared with dialysis in potential transplant candidates with a history of cancer have not been assessed, current clinical practice relies on evidence from observational studies and registry analyses.

Background Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain. Methods We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available. Results Thirty-six studies involving 10 535 transplant recipients were eligible. There was moderate quality evidence that transplant recipients who developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR) [relative risk (RR) 9.66; 95% confidence interval (CI) 6.79-13.73, 16 studies, n = 4174]. For all other outcomes, the evidence was low to very low due to moderate-high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95% CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and transplant glomerulopathy RR 6.78; 95% CI 4.31-10.66, 3 studies, n = 1617, very low-quality evidence; and graft loss RR 4.95; 95% CI 3.81-6.43, 19 studies, n = 5473, low-quality evidence). Meta-regression indicated that deceased kidney donation (R2 = 1.00, P

Supplemental Digital Content is available in the text., Background. World Health Assembly Resolution 63.22 mandated World Health Organization to facilitate Member State access to appropriate information on medical products of human origin (MPHO), including collecting data on serious adverse events and reactions. To meet this challenge, the Italian National Transplant Center, with a mandate from World Health Organization, has built and maintained an open-access searchable database of instructive records on disease transmission and other MPHO adverse occurrences. Methods. One record in the Notify Library describes a specific type of adverse occurrence in 1 type of MPHO and might be linked with 1 or multiple different references. The record inclusion criteria are that it has been reliably documented in a published article or official vigilance reporting system and that it has instructive value for the fields of transfusion, transplantation, or assisted reproduction. The selection and review of references for publication is performed by international experts who collaborate in 5 topic-specific editorial groups: infection transmission, malignancy transmission, living-donor reactions, process-related incidents, and clinical complications. New relevant references are identified through systematic searches and proactive communication by the experts. Results. The Library contains 1733 records, quoting 2632 references. Of the records, 41.8% are related to organs, 20.8% to blood and blood components, 16.5% to hematopoietic progenitor cells, 15.2% to tissues, 4.2% to reproductive tissues and cells, and 1.5% to other MPHO. Conclusions. Notify Library is the first open-access, searchable database of systematically identified reports of disease transmission and other adverse occurrences arising from the donation and clinical application of MPHO.

Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation. We evaluated i-IFTA in 429 indication- and 2052 protocol-driven biopsy samples from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time course, and relationships with T cell-mediated rejection (TCMR), immunosuppression, and outcome. Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation and followed by IF/TA. The prevalence and intensity of i-IFTA increased with developing chronic fibrosis and correlated with inflammation, tubulitis, and immunosuppression era (P

Background: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision-making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. Methods: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During Round 2 and 3, participants re-rated the outcomes after reviewing their own score, the distribution of the respondents’ scores, and comments. We calculated the median, mean, and proportion rating 7-9 (critically important), and analyzed comments thematically. Results: 1018 participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed Round 1, and 779 (77%) completed Round 3. The top eight outcomes that met the consensus criteria in Round 3 (mean ≥7.5, median ≥8 and proportion >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin) and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to six outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified five themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. Conclusions: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation.

International audience; BACKGROUND: Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. METHODS: We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. RESULTS: Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders-inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. CONCLUSIONS: Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.

Aim This study aims to describe patients' perspectives on the transition to home haemodialysis. Methods Up to three sequential semi-structured interviews were conducted with 20 patients during the transition to home haemodialysis at an Australian renal unit. Transcripts were analysed thematically. Participants completed a satisfaction questionnaire after commencing home haemodialysis. Results We identified six themes: persevering despite trepidations (diminishing intimidation of machinery, acquiescing to fatal risks, reconciling fears of cannulation, dispelling concerns of neglect and tolerating necessary concessions); optimizing the learning pathway (practising problem solving, learning from mistakes, grasping technical complexity, minimizing cognitive overload and progressing at own pace); developing confidence (believing in own abilities, adapting to independence, depending on caregiver partnership and faith in crisis support); interrupted transition momentum (lacking individual attention, language barriers, installation delays, interfering illness and complications and acclimatizing to new conditions); noticing immediate gains (reclaiming lifestyle normality, satisfying self-sufficiency, personalizing treatment regime and thriving in a positive environment); and depleting resources and energy (exhaustion with gruelling routine, confronting medicalization of the home, draining financial reserves and imposing family burden). Fewer than 30% of respondents indicated low satisfaction with staff availability domains, staff interpersonal domains or technical domains. Conclusion Home haemodialysis training fosters confidence in patients; however, many patients experience stress because of medical isolation, treatment responsibilities, family impositions and financial difficulties. Addressing patient's on-going psychosocial concerns may alleviate burdens on patients and their families during the transition to home haemodialysis.

Prolonged ischemia is a known risk factor for delayed graft function (DGF) and its interaction with donor characteristics, the pathways of donor death, and graft outcomes may have important implications for allocation policies.Using data from the Australian and New Zealand Dialysis and Transplant registry (1994-2013), we examined the relationship between total ischemic time with graft outcomes among recipients who received their first deceased donor kidney transplants. Total ischemic time (in hours) was defined as the time of the donor renal artery interruption or aortic clamp, until the time of release of the clamp on the renal artery in the recipient.A total of 7542 recipients were followed up over a median follow-up time of 5.3 years (interquartile range of 8.2 years). Of these, 1823 (24.6%) experienced DGF and 2553 (33.9%) experienced allograft loss. Recipients with total ischemic time of 14 hours or longer experienced an increased odd of DGF compared with those with total ischemic time less than 14 hours. This effect was most marked among those with older donors (P value for interaction = 0.01). There was a significant interaction between total ischemic time, donor age, and graft loss (P value for interaction = 0.03). There was on average, a 9% increase in the overall risk of graft loss per hour increase in the total ischemic time (adjusted hazard ratio, 1.09; 95% confidence interval, 1.01-1.18; P = 0.02) in recipients with older donation after circulatory death grafts.There is a clinically important interaction between donor age, the pathway of donor death, and total ischemic time on graft outcomes, such that the duration of ischemic time has the greatest impact on graft survival in recipients with older donation after circulatory death kidneys.

Background Slow recruitment and poor retention jeopardize the reliability and statistical power of clinical trials, delaying access to effective interventions and increasing costs, as commonly observed in nephrology trials. Involving patients in trial design, recruitment and retention is infrequent but potentially transformational. Methods We conducted three workshops involving 105 patients/caregivers and 43 health professionals discussing patient recruitment and retention in clinical trials in chronic kidney disease. Results We identified four themes. ‘Navigating the unknown’—patients described being unaware of the research question, confused by technical terms, sceptical about findings and feared the risk of harm. ‘Wary of added burden’—patients voiced reluctance to attend additional appointments, were unsure of the commitment required or at times felt too unwell and without capacity to participate. ‘Disillusioned and disconnected’—some patients felt they were taken for granted, particularly if they did not receive trial results. Participants believed there was no culture of trial participation in kidney disease and an overall lack of awareness about opportunities to participate. To improve recruitment and retention, participants addressed ‘Building motivation and interest’. Conclusions Investigators should establish research consciousness from the time of diagnosis, consider optimal timing for approaching patients, provide comprehensive information in an accessible manner, emphasize current and future relevance to them and their illness, involve trusted clinicians in recruitment and minimize the burden of trial participation. Participation in clinical trials was seen as an opportunity for people to give back to the health system and for future people in their predicament.

The impact of the COVID-19 pandemic is very wide and occupies almost every aspect of life across the world with the wave of direct health impacts cutting across each nation at different paces. The impact on the economies of all countries has been dramatic and has yet to become fully apparent. The effect of the pandemic on the health of transplant patients has been extensive with data published across a number of journals from both single centers and regional and national databases. It is becoming clear that transplant patients are more likely to catch SARS-CoV-2 and when infected have a much increased mortality risk. Impact on clinical services, through reduction in intensive care unit bed availability and decreased deceased organ donors, as well as diversion of clinical staff and other resources from transplantation, has led to dramatic decreases in clinical transplant activity. We have documented these impacts through the pages of Transplantation and through the COVID-19 Transplantation map established with the cooperation of The Transplantation Society.1,2 What has not yet been documented to any degree so far is the impact on clinical and basic laboratory research in Transplantation. This round up of experiences from around the world shows substantial closure and diversion of effort from Transplantation research both in the clinic and in the laboratory with a future that is uncertain. Some countries and some centers have been more impacted than others. We hope by illuminating this feature of the pandemic we can assist in resuscitating research in our field as soon as compatible with the phases of the pandemic in each country.

The bidirectional relationship between cancer and chronic kidney disease (CKD) is complex. Patients with cancer, particularly those with hematological malignancies such as multiple myeloma and lymphoma, are at increased risk of developing acute kidney injury and CKD. On the other hand, emerging evidence from large observational registry analyses have consistently shown that cancer risk is increased by at least 2- to 3-fold in kidney transplant recipients, and the observed increased risk occurs not only in those who have received kidney transplants but also in those on dialysis and with mild- to moderate-stage CKD. The interactions between cancer and CKD have raised major therapeutic and clinical challenges in the management of these patients. Given the magnitude of the problem and uncertainties, and current controversies within the existing evidence, Kidney Disease: Improving Global Outcomes (KDIGO) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology to identify key management issues in nephrology relevant to patients with malignancy. This report covers the discussed controversies in kidney disease in hematological malignancies, as well as cancer after kidney transplantation. An overview of future research priorities is also discussed.

© 2020 Kidney Disease:Improving Global Outcomes (KDIGO)The association between kidney disease and cancer is multifaceted and complex. Persons with chronic kidney disease (CKD) have an increased incidence of cancer, and both cancer and cancer treatments can cause impaired kidney function. Renal issues in the setting of malignancy can worsen patient outcomes and diminish the adequacy of anticancer treatments. In addition, the oncology treatment landscape is changing rapidly, and data on tolerability of novel therapies in patients with CKD are often lacking. Caring for oncology patients has become more specialized and interdisciplinary, currently requiring collaboration among specialists in nephrology, medical oncology, critical care, clinical pharmacology/pharmacy, and palliative care, in addition to surgeons and urologists. To identify key management issues in nephrology relevant to patients with malignancy, KDIGO (Kidney Disease: Improving Global Outcomes) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology in December 2018. This report covers issues related to kidney impairment and solid organ malignancies as well as management and treatment of kidney cancer. Knowledge gaps, areas of controversy, and research priorities are described.

BACKGROUND Interstitial inflammation (i-INT) is the driver of T-cell-mediated rejection. Its causes, pathophysiology, kinetics, and outcomes are poorly documented. METHODS The role of i-INT was evaluated in 2055 biopsies from 775 renal transplant recipients. RESULTS i-INT was present in 374 (18.2% prevalence) from acute and subclinical rejection (67.4%); interstitial fibrosis and tubular atrophy (14.4%); BK virus nephropathy (BKVAN) 9.9%; and acute tubular necrosis (ATN with i-INT) in 5.9% of cases. i-INT was predicted by prior T-cell-mediated rejection and BKVAN, human leukocyte antigen mismatch, cyclosporine therapy, and indication biopsy for dysfunction. It correlated with tubulitis, arteritis, and antibody markers within concurrent histology (P < 0.001). After treatment, renal functional recovery was best with histological ATN, milder i-INT, and early posttransplant biopsy times. The initial histological improvement of inflammation depended on baseline i-INT severity. Complete resolution to Banff i0 was predicted by early biopsy time, antilymphocyte therapy, recipient age, and medication compliance (all P < 0.001). Clearance i-INT was followed by delayed resolution of tubulitis (P < 0.001). i-INT was associated with histological ATN, renal dysfunction, and increased incident fibrosis on sequential pathology. Progressive fibrosis following related-rejection i-INT was dependent on tubulitis using multivariable analysis. In contrast, fibrogenesis after BKVAN or ATN was unrelated to inflammation. i-INT cases were followed by recurrent rejection in 35.3%, increased graft loss, and greater patient mortality. Multiple complementary outcome analyses determined the optimal lower diagnostic threshold for inflammation was Banff i1 score. CONCLUSIONS i-INT is a heterogeneous pathological phenotype that results in adverse functional and structural outcomes, for which active and robust therapy should be considered.

Background In patients with CKD, the risk of developing colorectal cancer is high and outcomes are poor. Screening using fecal immunochemical testing (FIT) is effective in reducing mortality from colorectal cancer, but performance characteristics of FIT in CKD are unknown. Methods To determine the detection rates and performance characteristics of FIT for advanced colorectal neoplasia (ACN) in patients with CKD, we used FIT to prospectively screen patients aged 35–74 years with CKD (stages 3–5 CKD, dialysis, and renal transplant) from 11 sites in Australia, New Zealand, Canada, and Spain. All participants received clinical follow-up at 2 years. We used a two-step reference standard approach to estimate disease status. Results Overall, 369 out of 1706 patients who completed FIT (21.6%) tested positive; 323 (87.5%) underwent colonoscopies. A total of 1553 (91.0%) completed follow-up; 82 (4.8%) had died and 71 (4.2%) were lost. The detection rate of ACN using FIT was 6.0% (5.6%, 7.4%, and 5.6% for stages 3–5 CKD, dialysis, and transplant). Sensitivity, specificity, and positive and negative predictive values of FIT for ACN were 0.90, 0.83, 0.30, and 0.99, respectively. Of participants who underwent colonoscopy, five (1.5%) experienced major colonoscopy-related complications, including bowel perforation and major bleeding. Conclusions FIT appears to be an accurate screening test for patients with CKD, such that a negative test may rule out the diagnosis of colorectal cancer within 2 years. However, the risk of major complications from work-up colonoscopy are at least ten-fold higher than in the general population.

International audience; Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. Databases were searched to October 2016. We synthesized the findings descriptively. The 28 studies (n~=~2071 participants) addressed kidney [9 (32%)], heart [7 (25%)], liver [3 (11%)], lung [1 (4%)], pancreas [1 (4%)], and nonspecified organ transplantation [7 (25%)] using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique. Nine (32%) reported patient involvement. The 336 research priorities addressed the following: organ donation [43 priorities (14 studies)]; waitlisting and allocation [43 (10 studies)]; histocompatibility and immunology [31 (8 studies)]; immunosuppression [21 (10 studies)]; graft-related complications [38 (13 studies)]; recipient (non-graft-related) complications [86 (14 studies)]; reproduction [14 (1 study)], psychosocial and lifestyle [49 (7 studies)]; and disparities in access and outcomes [10 (4 studies)]. The priorities identified were broad but only one-third of initiatives engaged patients/caregivers, and details of the process were lacking. Setting research priorities in an explicit manner with patient involvement can guide investment toward the shared priorities of patients and health professionals.