BACKGROUND:As the demand for living donor kidney transplantation increases, transplant programs have increasingly accepted hypertensive kidney donors. However, the safety of this practice remains unclear. This systematic review and meta-analysis aims to evaluate cardiovascular and kidney outcomes in living kidney donors with and without preexisting hypertension. METHODS:We performed a systematic search across MEDLINE, EMBASE, Cochrane CENTRAL, and EBM databases up to 1 October 2024. The exposure group consisted of living kidney donors with hypertension, while the comparator group included those without hypertension. Primary outcomes included differences in survival, major adverse cardiovascular events (MACE), estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m² or less, and development of kidney failure, defined as requiring dialysis or a transplant. Risk differences (proportion of participants experiencing the outcome in the hypertensive group minus the proportion in the normotensive group, risk difference) for mortality, MACE, kidney failure, and eGFR ≤ 45 mL/min/1.73 m² were pooled for synthesis. RESULTS:Of the 983 studies screened, 17 were included, totaling 4,881 hypertensive and 40,565 normotensive kidney donors. The mean (SD) age at donation was 48.9 (18.1) years, with a median (IQR) follow-up of 5.0 (2.0-7.1) years. Hypertensive donors showed a significantly higher risk of death (RD 40.0 per 1,000 person years, 95% confidence interval (CI) 4.0, 70.0; P = 0.03), but no significant differences in kidney failure (RD 1.0 per 1,000 person years, 95% CI (0.3, 2.6); P = 0.13), eGFR ≤ 45 mL/min/1.73 m² (RD 20.0 per 1,000 person years, 95% CI, -90.0, 140.0; P = 0.69), or MACE (RD 3.0 per 1,000 person years, 95% CI, -90.0, 160.0; P = 0.58). CONCLUSIONS:This review suggests that hypertensive living kidney donors have a higher risk of death compared to normotensive donors, but no increased risk for kidney failure, low eGFR, or MACE. However, further long-term studies are needed, particularly for younger hypertensive donors.

INTRODUCTION:The cause of kidney failure in kidney transplant recipients remains unknown in 20-45% of cases. Outcomes for living kidney donors (LKDs) are generally excellent, with only 8% experiencing complications post-donation. Here, we hypothesize that genetic testing could identify a genetic etiology in at least 20% of recipients and inform risk stratification in LKDs. METHODS:Genetic testing was performed in 231 transplant recipients and 46 prospective LKDs by means of exome sequencing of 409 chronic kidney disease (CKD)-associated genes. We also assessed 122 retrospective LKDs who developed adverse kidney outcomes post-donation which were defined by at least two of the three criteria: hypertension, a glomerular filtration rate under 60 mL/min/1.73m2, or a urine albumin to creatinine ratio of 3 mg/mmol or more. RESULTS:Pathogenic or likely pathogenic (P/LP) variants were identified in 23% of recipients, most commonly involving genes associated with cystic kidney disease and glomerulopathies. Among the recipients with a genetic diagnosis, there was a 37% rate of reclassification to a different phenotype post genetic testing. Among prospective LKDs, 4% had P/LP variants. In the retrospective cohort of LKDs with adverse kidney outcomes post donation, 19% carried P/LP variants. CONCLUSIONS:Genetic testing yielded a high diagnostic rate and frequently reclassified CKD etiology in transplant recipients, underscoring its diagnostic utility. Universal genetic testing of asymptomatic LKDs had a yield of 4%, although our prospective LKD cohort had limited sample size. In contrast, high proportion of LKDs with adverse kidney outcome post-donation were found to carry P/LP variants in CKD-associated genes. Our findings suggest that targeted genetic testing of high-risk donors may be a preferred over universal testing strategy to optimize donor selection in LKDs. However, further evaluation is warranted to ensure this approach appropriately balances donor safety with equitable access.

Background:Females develop hypertension later and are less likely to receive chronic kidney disease (CKD) prevention treatments. The long-term impact of these differences remains unclear. We aimed to investigate sex-based differences in the in CKD outcomes among older adults with hypertension. Methods:We conducted a population-based retrospective cohort study of adults aged ≥66 years with new hypertension using linked health data from Ontario, Canada (1 January 2010, to 31 December 2021). The primary composite outcome was a 40% decline in estimated glomerular filtration rate (eGFR) or kidney failure. We used Cox proportional hazards models to calculate hazard ratios (HRs) and Fine-Gray models accounting for death as a competing risk (subdistribution HRs, sHRs). Results:Incident hypertension developed in 121 490 individuals (57.7% female; mean age 73.1 years; mean eGFR 83.2 mL/min/1.73 m²; median follow-up 6.8 years), 17 343 (14.3%) experienced the composite kidney outcome. The crude incidence rate per 1000 person-years was higher for females compared with males (22.0 in females vs 21.1 in males; P < .001). Females had a higher adjusted risk of the primary outcome, after accounting for death {sHR 1.10 [95% confidence interval (CI) 1.07-1.14]}. Females had a higher crude incidence of eGFR <60 mL/min/1.73 m² than males (66.6 vs 59.4; P < .001), and a higher adjusted risk [sHR 1.15 (95% CI 1.13-1.18)]. For eGFR <45 mL/min/1.73 m², females had a higher crude incidence (19.2 vs 17.5; P < .001) and a higher adjusted risk [sHR 1.13 (95% CI 1.10-1.17)] compared with males. Conclusion:Older females with new onset hypertension were more likely to develop a 40% decline in eGFR or kidney failure compared with older males. This study will inform hypertension management practices in aging populations.

ABSTRACT:Although physicians with disabilities are underrepresented in medicine, their lived experiences of disability can increase empathy for patients, enrich the learning environment, and improve working conditions. However, they face barriers related to procedures, policies, clinical accommodations, disability and wellness support services, and physical environments as well as cultural barriers that affect their meaningful inclusion and ability to work at their full capacity. Despite national Canadian physician organizations recommending accommodations and inclusive policies and practices, an environmental scan of the top 10 ranked Canadian hospital institutions in April-May 2020 did not identify any existing accommodations policies.The Medical Advisory Committee and senior management team at The Ottawa Hospital (TOH) formally endorsed the first position statement in Canada supporting physicians with disabilities in 2021, which led to the establishment of a process to develop and implement an accessibility and accommodations policy for the Department of Medicine (DOM) at TOH. After careful review and an iterative development process, the DOM approved a formal Accessibility and Accommodations Policy in June 2022. The policy ensures physicians are accommodated during the recruitment, interview, and appointment phases. It outlines a process for the development of an accommodation plan, addresses funding for accommodations, protects physicians returning to work following absences due to a disability, and requires exploration of opportunities for physicians to make a meaningful contribution if they cannot practice clinically due to their disability.In this article, the authors discuss the process of developing and implementing the DOM Accessibility and Accommodations Policy, outline the key elements of the policy, and discuss broader implementation of the policy and how they are monitoring its impact. They also discuss the importance and benefits of collecting data on physicians who self-identify as having a disability and, through confidential surveys, focus groups, and interviews, monitoring the impact of accessibility and accommodations policies.

Introduction Predictive scoring systems support clinicians in decision-making by estimating the prognosis of patients in intensive care units (ICUs). However, there is limited evidence on the accuracy of these systems in predicting mortality and organ dysfunction in special populations. The aim of this review is to assess the performance of predictive scoring systems in forecasting mortality in adult ICU patients in relation to baseline kidney function. It is anticipated that the assessment of predictive scoring systems’ performance and patient outcomes in this review may reveal information that will contribute to improve the quality of care and outcomes for special or under-represented ICU patient populations. It might also inform future research and contribute to the development of novel risk prediction models to address identified gaps or unanswered questions.Methods and analysis This review will include only observational studies, as these allow us to assess the real-world performance of predictive scoring systems in ICU settings by examining the original validation studies. By excluding randomised trials, paediatric studies, case reports and machine learning-derived models, this review focuses on the direct practical use of the scoring systems in adult ICU patients. A comprehensive search of MEDLINE, Embase and Scopus was conducted from database inception to 10 October 2024. The data will be extracted on study characteristics, patient outcomes and performance metrics.Ethics and dissemination This review will analyse data from previously published studies; no ethical approval is required. All data that will be included in the analysis will be publicly available and will be included in the final manuscript. Results will be disseminated through publication in a peer-reviewed journal and will also be presented at seminars and conferences.PROSPERO registration number CRD42024611547.

Background:Some men who donate a kidney have reported testicular pain after donation; however, attribution to donation is not clear as no prior studies included a comparison group of nondonors. Objective:To examine the proportion of male donors who reported testicular pain in the years after nephrectomy compared to male nondonors with similar baseline health characteristics. Design Participants and Setting:We enrolled 1042 living kidney donors (351 male) before nephrectomy from 17 transplant centers (12 in Canada and 5 in Australia) from 2004 to 2014. A concurrent sample of 396 nondonors (126 male) was enrolled. Follow-up occurred until November 2021. Measurements:Donors and nondonors completed the same schedule of measurements at baseline (before nephrectomy) and follow-up. During follow-up, participants completed a questionnaire asking whether they had experienced new pain in their eyes, hands, or testicles; those who experienced pain were asked to indicate on which side of the body the pain occurred (left or right). The pain questionnaire was completed by 290 of 351 male donors (83%) and 97 of 126 male nondonors (77%) a median of 3 years after baseline (interquartile range = 2-6). Methods:Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. After weighting, the nondonor sample increased to a pseudo sample of 295, and most baseline characteristics were similar between donors and nondonors. Results:At baseline, donors (n = 290) were a mean age of 49 years; 83% were employed, and 80% were married; 246 (84.8%) underwent laparoscopic surgery and 44 (15.2%) open surgery; 253 (87.2%) had a left-sided nephrectomy and 37 (12.8%) a right-sided nephrectomy. In the weighted analysis, the risk of testicular pain was significantly greater among donors than nondonors: 51/290 (17.6%) vs 7/295 (2.3%); weighted risk ratio, 7.8 (95% confidence interval [CI] = 2.7 to 22.8). Donors and nondonors did not differ statistically in terms of self-reported eye pain or hand pain. Among donors, the occurrence of testicular pain was most often unilateral (92.2%) and on the same side as the nephrectomy (90.2%). Testicular pain occurred more often in donors who had laparoscopic vs open surgery: 48/246 (19.5%) vs 3/44 (6.8%) but was similar in those who had a left-sided vs right-sided nephrectomy: 44/253 (17.4%) vs 7/37 (18.9%). Limitations:Participants recalled their symptoms several years after baseline, and we did not assess the timing, severity, or duration of pain or any treatments received for the pain. Conclusion:Unilateral testicular pain on the same side of a nephrectomy is a potential complication of living kidney donation that warrants further investigation.

The renin-angiotensin system (RAS) is involved in kidney fibrosis. We previously identified six RAS-regulated proteins (RHOB, BST1, LYPA1, GLNA, TSP1, and LAMB2) that were increased in the urine of patients with kidney allograft fibrosis, compared to patients without fibrosis. We hypothesized that these urinary RAS-regulated proteins predicted primary outcomes in kidney transplant recipients enrolled in the largest RAS inhibitor randomized controlled trial. Urine excretion of 10 peptides corresponding to the six RAS-regulated proteins was quantified using parallel reaction monitoring mass spectrometry assays (normalized by urine creatinine) in a subset of patients in the trial. Machine learning models predicting outcomes based on urine peptide excretion rates were developed and evaluated. Urine samples (n = 111) from 56 patients were collected at 0, 6, 12, and 24 months. Twenty-four primary outcomes (doubling of serum creatinine, graft loss, or death) occurred in 17 patients. Logistic regression utilizing eight peptides of TSP1, BST1, LAMB2, LYPA1, and RHOB, from the last urine sample prior to outcomes, predicted a graft loss with an AUC of 0.78 (p = 0.00001). A random forest classifier utilizing BST1 and LYPA1 peptides predicted death with an AUC of 0.80 (p = 0.0016). Urine measurements of RAS-regulated proteins may predict outcomes in kidney transplant recipients, although further prospective studies are required.

Underutilization of deceased donor organs has worsened the gap in the number of kidneys available for transplantation. The purpose of this clinical practice guideline is to provide recommendations on the utilization of donor kidneys at risk of discard. Six conditional recommendations were made all with very low certainty of evidence: 1) We suggest utilizing extended criteria donor (ECD) kidneys for transplantation rather than remaining on the wait list and continuing with dialysis; 2) We suggest utilizing kidneys from ECD versus non-ECD in selected transplant candidates; 3) We suggest that organs from older kidney donors can be used in selected transplant candidates who may derive benefit from them; 4) We suggest that kidneys from deceased donors with acute kidney injury can be used for transplantation based on clinician assessment and donor factors; 5) We suggest that donor kidneys with acute kidney injury from either ECD or non-ECD be used for kidney transplantation; 6) We suggest using kidneys from donors after death determination by circulatory criteria for transplantation. This clinical practice guideline provides evidence for the use of deceased donor kidneys that are at risk of discard and may improve the shared decision-making between transplant physicians and wait-listed patients.

Cancer is a major cause of morbidity and mortality in kidney transplant recipients. Health professionals have a critical role in promoting cancer screening participation. From March 2023 to February 2024, an online survey was distributed to kidney transplant health professionals globally to assess their screening practices. We compared their reported screening practices to recommended guidelines and analyzed factors associated with these practices. We received 97 responses, and most were nephrologists (70%), and around 80% recommended breast, colorectal, and cervical cancer screening for kidney transplant candidates and recipients. About 85% recommended lung cancer screening for higher-risk individuals. Skin cancer screening recommendations varied from 69% for transplant candidates and 84% for recipients. Self-reported cervical cancer screening practices were most concordant with recommended guidelines, followed by breast and skin cancers. Barriers reported included a lack of cancer screening awareness (28%), perceived financial constraints (35%), and deficient structured cancer screening systems (51%). Professionals from high-income countries were more likely to advise screening than those from lower-middle-income countries, with odds ratios ranging from 2.9 to 12.3. Most health professionals reported recommending cancer screening for kidney transplant candidates and recipients. However, recommendations were influenced by costs and service delivery gaps within health systems.

Importance:Recent guidelines call for better evidence on health outcomes after living kidney donation. Objective:To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared. Design, Setting, and Participants:Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. Exposure:Living kidney donation. Main Outcomes and Measures:Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]). Results:Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19). Conclusions and Relevance:In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up. Trial Registration:ClinicalTrials.gov Identifier: NCT00936078.

Introduction Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk.Methods and analysis We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation.Ethics and dissemination We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309).Trial registration number NCT05148715.

BACKGROUND:Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS:We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m 2 (milliliter per minute per 1.73 m 2 , as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS:Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m 2 ). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology Collaboration Cr/CysC equation. CONCLUSIONS:Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.

Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.

BACKGROUND:High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES:To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uraemic Pruritus in Dialysis patients (UP-Dial) 14-item scale, by comparing haemodialysis and peritoneal dialysis modality. METHODS:This validation study used data from the Thai Renal Outcomes Research-Uraemic Pruritus, a prospective, multicentre, longitudinal study. Data for this study were collected from 1 February 2019 to 31 May 2022. The adult sample of 226 haemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across haemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8) and Patient Health Questionnaire-9 (PHQ-9). RESULTS:From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73-0.74) with global itching, a positively moderate correlation (0.33-0.58) with DLQI, PSQI, global fatigue, SSS-8 and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation 0.84-0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS:The findings reaffirm good measurement properties of the UP-Dial 14-item scale in haemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

IntroductionLiving donor kidney transplantation (LDKT) is the best treatment option for patients with kidney failure. Efforts to increase LDKT have focused on microlevel interventions and the need for systems thinking has been highlighted. We aimed to identify and compare health system–level attributes and processes that are facilitators and barriers to LDKT.MethodsWe conducted a qualitative comparative case study analysis of 3 Canadian provincial health care systems with variable LDKT performance (Quebec: low, Ontario: moderate-high, British Columbia: high). Data collection entailed semistructured interviews (n = 91), document review (n = 97) and focus groups (n = 5 with 40 participants), analyzed using inductive thematic analysis.ResultsOur findings showed a strong relationship between the degree of centralized coordination between governing organizations and the capacity to deliver LDKT as follows. (i) macro-level coordination between governing organizations in British Columbia and Ontario increased capacities, whereas Québec was seen as decentralized with little formal coordination; (ii) a higher degree of centralized coordination facilitated more effective resource deployment in the form of human resources and initiatives in British Columbia and Ontario, whereas in Québec resource deployment relied on hospital budgets leading to competition for resources and reduced capacity of initiatives; (iii) informal resource sharing through strong communities of practice and local champions facilitated LDKT in Ontario and British Columbia and was limited in Québec.ConclusionOur findings suggest that interventions that account for full-system function, particularly macro-level coordination between governing organizations can improve LDKT delivery. Findings may be used to guide structured organizational change toward increasing LDKT and mitigating the global burden of kidney failure.

Infection is inconsistently measured and reported across kidney transplant trials. There is no standardized definition, in part because it is unclear which infection outcome measures are important to patients and clinicians. In a systematic review of randomized trials in kidney transplant recipients published between 2010 and 2019, infections were reported in only 38% of 397 trials, with 113 different outcome measures reported.1 The need to standardize reporting of critically important outcomes has been advocated to improve interpretation of trial-based evidence to inform care.2-4 The international Standardized Outcomes in Nephrology (SONG) initiative aims to establish a set of core outcome measures across the kidney disease spectrum based on shared priorities of patients, caregivers, clinicians, researchers, policy makers, and industry.5 Infection was identified as a core outcome domain in kidney transplantation based on consensus among 1200 patients, caregivers, and health professionals from >70 countries.6-8 CONTEXT AND SCOPE The international SONG kidney transplant infection consensus workshop was convened virtually in November 2021. Stakeholders discussed the implementation of an infection core outcome measure to be reported in all kidney transplant trials. The proposed core outcome for discussion was infection-related hospitalization.9,10 PARTICIPANTS AND CONTRIBUTORS Patients, caregivers, and health professionals with current or previous kidney transplantation experience were invited to the workshop. Invitations were also extended to representatives of professional societies, regulatory agencies, nephrology journals, registries, funding organizations, industry, and guideline organizations. In total, 59 participants (12 patients, 3 caregivers, and 44 health professionals) from 12 countries attended, and 16 contributors provided feedback on the workshop materials (Table S1, SDC, https://links.lww.com/TP/C905). WORKSHOP PROGRAM AND MATERIALS The workshop program, background material, and interim survey results were sent to participants 2 wk in advance of the workshop. Participants were allocated to 1 of 6 breakout discussion groups. Each group had 8 to 12 members, including 2 to 4 patients/caregivers. Participants discussed interim survey results, including potential core outcome measures.10 Group facilitators (E.M., A.V., S.C., Y.C., G.W., and S.Ca.) received training and a question guide (Table S2, SDC, https://links.lww.com/TP/C905). All breakout and plenary discussions were audiotaped and transcribed; transcripts were entered into HyperRESEARCH (ResearchWare Inc; version 3.0.) to facilitate coding and data analysis. SUMMARY OF THE WORKSHOP DISCUSSION We identified 3 themes from the discussion (Table 1). The breakout groups that contributed to these themes are shown in Table S3 (SDC, https://links.lww.com/TP/C905). TABLE 1. - Selected quotations from the workshop discussions on the identification and implementation of a core infection outcome measure in kidney transplantation Hospitalization capturing the burden of infection An indicator for severe infection "Admission to hospital reflects something about the severity of infection."—H4"The advantage of sticking with the hospitalisation is that it captures the severity of problem."—H4"Admission to hospital is a very clean and helpful endpoint as it is indicating severity."—H5"Burden on the patient is captured in hospitalisation."—H6"The advantage of sticking with the hospitalization is that it captures the severity of problem or real complications rather than more preventative monitoring."—H6"We know there is a lot of infection around and admission to hospital would be an important outcome measure for trials."—P1"Going into hospital is a marker of severity."—P4"I see hospitalisation as a key lifeline to me for treatment as it is a marker the severity of my underlying infection."—P6"Going into hospital reflects the vulnerability of the patient and how easy it is for them to tip over."—C2 Limiting life participation "It takes away a lot of quality of life, the career was always long on dialysis already and they had so multiple hospitalisations, they don't want to come anymore."—H1"It is all about the wellbeing. When you go back to work or you go back to school or you, you can go out and do all the things we normally do. When do you feel able to get on with life again."—P2"Being in hospital with an infection means that I have been unable to go shopping … gardening … going to the movies … playing with my grandchildren."—P3"You actually get back to doing the shopping or whatever it is you do day-to-day your day-to-day life. That should be your end point and how long ever it takes to get there is the physical outcome."—H4"The UTI that requires intravenous treatment can make you not being able to go to work, having to cancel a trip, not participate in the daughter's wedding."—H6 Accounting for practice patterns and resource availability Variability in treatment of infection across health systems "And it's quite easy in some regions to do the diagnostics in a clinic, for example, if they are not, of course, in sepsis or something. In other places, they are hospitalised for very, let's say trivial infections, which really not always need hospitalisation. So, there is a huge variability. And I think that is important to consider (with) hospitalisation."—H2"We may measure different practices rather than the different severities of an infection that pragmatic measure."—H4"This is the heterogeneity in how a hospitalization is managed, how hospitalization stays could represent in different patient profile, how does this health system deal with different things and different ways because of flow, availability of bed, resources, and so on."—H4"Hospitalisation varies quite a lot depending on your health system."—H5"In Australia, once acute care is finished, we may be transitioning to an ambulatory outpatient care with more frequent visits."—P3"Even milder infection will need to admit the patient for one, two or four weeks of intravenous infusions."—C4 Use of composite outcomes for granularity and efficiency "The length of follow-up may be inadequate to characterize the safety profile of a therapy and the treatment effect may be driven by components of lesser importance."—H3"Composite outcomes for infection may help understand the severity … for example, we can break it down into things like outpatient management, inpatient stuff like going into hospital, or intensive care setting or measure it like infection-associated death."—H4"You collecting data on hospitalisation in clinical trials will help us understand why patients are being admitted and look at preventative strategies to reduce admissions."—H4"Composite outcomes help detect an increased event rate."—H5"You have to have a composite outcome in order to have a statistical significant with a smaller sample size."—H5 Enhancing feasibility for implementation Minimizing completion burden "Hospitalisation is useful from a trialist perspective in terms of it occurred with a reasonable number of events, so you could get adequate power from a not too large trial."—H2"Infections requiring hospitalisations would be a sensible outcome measure to use as this would be practically easy for a clinical nurse, clinical trialist, and so on to record data."—H3"It could be easily practically implemented particularly as SAEs (severe adverse events) are recorded anyway and it is simply just using the information that has been recorded."—H3"It needed to be easy to measure, readily implemented in everyday practice. It also needs to minimise the burden on study investigators and to be measured easily in a clinical trial."—H5"Hospital admissions fulfil the definition of Serious Adverse Event which warrants exhaustive declaration by investigators and this information is already captured."—H6"Acknowledged the limitations by keeping it simple is a real strength."—C4 Avoiding ambiguity in the data "The number of days spent in hospital may reflect the economic burden and severity of the illness."—H1"The number of admissions to hospital is easy to collect because you simply count the number of admissions that the patient is admitted whereas the number of days admitted can cause confusion because you are curious to know whether the days spent in hospital is for infection related or not."—H5"You may go into hospital with a pneumonia and get better in a few days but stay in hospital because you develop diverticulitis and somehow end up getting a colonoscopy and end up staying in hospital for 3 months which does not have much to do with the infection."—H6"It is very clear. Hospitalization is important because that sort of gives me a guideline. And in mind, it tells me how bad infection is and in a year, if I've been hospitalised three or four times, then I am in a really bad state and that would affect my graft function. Hospitalisation is definitely a good measure for and the duration as well."—P4"It is very clear about the number of admissions. You generally don't go into hospital unless you need to and that reflects severity, and it is easy to count."—P5"There's so many factors that impact on how long it takes, and it is not just the system, it is also how you respond to the treatment and how quickly."—P6"Hospitalization is definitely a good measure for and the number of times admitted per year is important because there is no confusion regarding whether the patient went into hospital or not."—C4 C, caregiver; H, health professional; P, patient; UTI, urinary tract infection. The number indicated (eg, H1) refers to the Group ID (1–6). HOSPITALIZATION CAPTURING THE OVERALL BURDEN OF INFECTION Indicating Severe Infection Participants suggested that hospitalization for infection was meaningful because it indicated severe infection. Health professionals remarked, "the advantage of sticking with the hospitalization is that it captures the severity of problems or real complications." Patients suggested that it was not possible to prioritize a specific type of infection, such as cytomegalovirus and BK virus, and capturing infection severity and impact was more important. For caregivers, hospitalization also indicated "vulnerability of the patient and how easy it is for them to tip over." Although some suggested that infection-related death or infection-related intensive care unit admission may also capture infection severity, these outcomes were considered less suitable Limiting Life Participation Participants supported infection-related hospitalization as a core outcome measure because it captured the detrimental impact of posttransplant infections on quality of life. Patients reported that hospitalization for transplant-related infections meant losing the ability to participate in activities of daily living, which was reinforced by health professionals. ACCOUNTING FOR VARIABILITY IN PRACTICE PATTERNS AND RESOURCING Variability in Infection Management Across Health Systems Participants asserted that the core outcome measure had to reflect international differences in infection management: "We may measure different practices rather than the different severities of an infection." Participants noted that the threshold for hospital admission for infection depended on factors including resources, hospital accessibility, and patient factors (eg, independence and comorbid profile), in addition to infection type and severity. International variability in hospital-based and general infection management was exemplified by health professionals: "in Australia, once acute care is finished, we may be transitioning to an ambulatory outpatient care with more frequent visits," and in South America, "even for milder infection, we will need to admit the patient for one, two, or four weeks of intravenous infusions." Use of Composite Outcomes for Granularity and Efficiency Consideration was given to using a composite outcome for infections to account for the full spectrum of infection severity and management. Components included outpatient treatment, infection-related hospitalization, infection-related intensive care unit admission, and infection-related death. Proponents of composite outcomes suggested trial cost savings by increasing event rates, thereby reducing study sample size. In contrast, disadvantages of composite outcomes raised by participants included "the length of follow-up may be inadequate to characterize the safety profile of a therapy." ENHANCING FEASIBILITY OF IMPLEMENTATION Minimizing Completion Burden For a core outcome measure to be reported across all kidney transplant trials, participants suggested that "it needed to be readily implemented in everyday practice … needed to minimize burden on study investigators and to be measured easily in a clinical trial." They also supported a simple definition that was easy to understand and commonly collected. Participants reported that hospitalization is considered a serious adverse event, and "this information is readily captured" in trials, which facilitated implementation. Avoiding Data Ambiguity Most participants asserted that defining the metric for the core outcome measure was important to avoid ambiguity. The metrics discussed were rate and duration of infection-related hospital admissions. Both metrics captured severity, but hospital admission rate was preferred over hospital duration because the latter may be confounded by intercurrent illnesses that prolong hospital stay. One patient summarized the views of many participants: "There's so many factors that impact on how long it takes and it is not just the system, it is also how you respond to the treatment and how quickly." SUMMARY AND DISCUSSION Infection-related hospitalization was identified as the most appropriate core outcome measure for kidney transplantation trials. It captured infection severity and quality of life impact irrespective of infection type and location. It was deemed feasible and implementable across different settings, given that hospital admissions are routinely collected as hospital administrative data and reported as a safety outcome in clinical trials. Limitations to the proposed core outcome measure were considered, including global variations in clinical practices and available resources, different thresholds for hospitalization due to infection, and inability to account for the full spectrum of infection severity. The use of a composite infection outcome consisting of infection-related death, hospital- and intensive care unit admission, or outpatient management was considered but deemed less suitable. Participants, including patients and caregivers, were from many countries, including high- and low-income countries, suggesting that the workshop's findings are readily transferable (Table 2). Notably, this workshop was conducted in English and, therefore, was not generalizable to non–English-speaking populations. Although only 2 participants were infectious disease specialists, 13 transplant infection experts attended the workshop. TABLE 2. - Proposed outcome measure for infections Proposed outcome measure Advantages Disadvantages Infection-related death Simple to collect as part of routine practice Captured already in SONG-Tx mortality core outcome, thereby duplicating data collection Infection requiring intensive care unit admission Captures the most severe infections Outcome measure not applicable to all settings due to lack of intensive care units in some hospitals Infection in the community or outpatient setting Able to assess infections that do not require inpatient admission Difficult to capture as part of a clinical trial Infection requiring hospitalization Easy to administer; simple to collect as part of routine practice Differences in clinical practices worldwide; inability to effectively capture the specifics of the infection SONG-Tx, Standardized Outcomes in Nephrology-Transplant. The themes derived from the discussion will contribute to outcome measure content validity. The measure will need to be assessed on the basis of Core Outcome Measures in Effectiveness Trials criteria, including content and structural validity, responsiveness, and measurement error.11 Establishing a valid, relevant, pragmatic, and readily available infection outcome measure is expected to improve the consistency and reliability of how infection is assessed and reported, reduce research waste, improve the certainty of evidence, and better inform decision-making in kidney transplantation. ACKNOWLEDGMENTS The authors thank the SONG Steering Committee and SONG Coordinating Committee for advice and comments. They thank the following organizations for their support: International: Cochrane Kidney and Transplant, Dialysis Outcomes and Practice Patterns Study, International Society of Nephrology, Kidney Disease | Improving Global Outcomes, PKD International, The Transplantation Society, and World Transplant Games Federation; Australia/New Zealand: Australian and New Zealand Society of Nephrology, Australian Kidney Trials Network, Christchurch Kidney Society, Kidney Health Australia, Caring for Australasians with Renal Impairment Kidney Health New Zealand, PKD Foundation of Australia, Renal Society of Australasia, and Transplant Australia; Canada: The Kidney Foundation of Canada, Canadian Society of Nephrology, and Canadian Society of Transplantation; Europe: British Kidney Patient Association, British Renal Society, European Kidney Patients Federation, European Kidney Transplant Association, European Society of Transplantation, European Renal Best Practice, UK National Kidney Federation, PKD Charity, Société Francophone de Transplantation, and The Renal Association; and America: American Association of Kidney Patients, Home Dialysis Central, National Kidney Foundation Southern California, and Sociedad Latinoamericana de Nefrología e Hipertensión. The following people attended the SONG-Tx Infection Consensus Workshop on ZOOM 2021: Adam Martin, Allison Tong, Andrea Matus Gonzalez, Andrea Viecelli, Andrew Demaine, Angela Wang, Anita van Zwieten, Ann Demaine, Anthony Preston, Benedicte Sautenet, Brenda De Coninck, Brooke Huuskes, Camille Kotton, Carmel Hawley, Chandana Guha, Christoph Wanner, Daniel Gossett, David Johnson, Deb Purdy, Dorcas Tarumbwa, Ellen Dobrijevic, Elmi Muller, Fritz Diekmann, Gene Tyson, Germaine Wong, Gillian Mundy, Greg Wilson, Helio Tesdesco-Silva, Jonathan Craig, Karine Manera, Kevin Abbott, Krista Lentine, Lorna Marson, Lucrezia Frurian, Luuk Hilbrands, Maarten Naesens, Maria Irene Bellini, Matty Hempstalk, Nicole Isbel, Nicole Scholes-Robertson, Paolo Ferrari, Patrick Rossignol, Paul Henman, Peter Reese, Rainer Oberbauer, Roberto Pecoits-Filho, Rosanna Cazzolli, Samuel Chan, Shyamsundar Muthuramalingam, Simon Carter, Tamara Al-Jabary, Tess Harris, Tom Vastani, Watanyu Parapiboon, Wim van Biesen, and Yeoungjee Cho.

Background and hypothesis. Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. Methods. We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada aged from 18 to 65 years from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (<= 10th, 5th, 2.5th, and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+), and kidney failure as well as each component individually. Results. From the age of 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for <= 10th, 96 to 63 for <= 5th, 90 to 58 for <= 2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at <= 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+, and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR, or albumin to creatinine ratio measure. Conclusions. eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Introduction A ‘healthy immigrant effect’ has been demonstrated for a number of chronic health conditions including cardiovascular disease, diabetes mellitus and dementia; however, the link between immigrant status and kidney health remains uncertain. We sought to compare the risk for incident chronic kidney disease (CKD) between Canadian immigrants and non-immigrants.Methods We conducted a population-level, observational cohort study of all adult (≥18 years of age) Ontario residents, including foreign-born immigrant Canadian citizens and non-immigrant Canadian citizens by birth, with normal baseline kidney function (outpatient estimated glomerular filtration rate (eGFR) ≥70 mL/min/1.73 m2) between 1 April 2007 and 30 September 2020 using provincial health administrative data. Multivariable Cox proportional hazard regression modelling was used to evaluate the relationship between immigrant status and the development of incident CKD (outpatient eGFR <60 mL/min/1.73m2).Results The study cohort included 10 440 210 Ontario residents, consisting of 22% immigrants (n=2 253 360) and 78% (n=8 186 850) non-immigrants. The mean (SD) age and eGFR were 45 (17) years and 102 (16) mL/min/1.73 m2, respectively, and 54% of individuals were female. A total of 117 028 immigrants (5%, 7 events per 1000 person-years) and 984 277 non-immigrants (12%, 16 events per 1000 person-years) developed incident CKD during follow-up. Immigrants experienced a 20% lower risk for incident CKD compared with non-immigrants (adjusted HR 0.80, 95% CI 0.80 to 0.81). Consistent findings were seen for refugee and non-refugee immigrants, immigrants with remote (1985–2004) and recent (2005–2020) landing dates, and immigrants from different world regions. Results were similar on re-defining incident CKD as two outpatient eGFR measurements <60 mL/min/1.73 m2 at least 90 days apart, treating death as a competing risk, and adjusting for baseline albuminuria.Conclusion Immigrants experience a lower risk for incident CKD compared with non-immigrants. These findings provide evidence of a ‘healthy immigrant effect’ in relation to kidney health.