Search

Background: Posttransplant diabetes mellitus (PTDM) is an important complication for solid organ transplant recipients (SOTRs). COVID-19 has been associated with an increased risk of incident diabetes in the general population. However, the association between COVID-19 and new-onset PTDM has not been explored., Methods: Using the National COVID Cohort Collaborative Enclave, we conducted a cohort study of adults without diabetes receiving a solid organ transplant (heart, lung, kidney, or liver) in the United States between April 1, 2020, and March 31, 2023, with and without a first diagnosis of COVID-19 (COVID+ versus COVID-) within 180 d of SOT. We propensity score matched a single COVID+ SOTR with a COVID- SOTR who was diabetes free at the same point posttransplant. Within this matched cohort, we used multivariable Cox proportional hazards models to examine the adjusted risk of PTDM associated with COVID+., Results: Among 1342 COVID+ SOTRs matched to 1342 COVID- SOTRs, the crude rate of newly diagnosed PTDM in the 2 y post-COVID was 17% in those with versus 13% in those without COVID-19 (P = 0.007). COVID-19 was significantly associated with new PTDM (adjusted hazard ratio, 1.37; 95% confidence interval, 1.12-1.68 at 2 y)., Conclusions: Similar to other viral infections, COVID-19 is associated with an increased risk of PTDM in SOTRs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Kidney transplant (KT) recipients have an increased risk of malignancy due to chronic immunosuppression. The emerging use of immune checkpoint inhibitors (ICIs) has been a promising development for the treatment of malignancy, but their use adds to the complexity of immunosuppression management for KT recipients. This case report describes 2 cases of acute rejection in KT recipients following ICI initiation and discusses the balance of malignancy treatment with adequate immunosuppression., Presenting Concerns of Patients: The first patient is a 44-year-old male KT recipient with a diagnosis of metastatic renal cell carcinoma presenting with acute kidney injury 6 days following initiation of an ICI. The second patient is a 73-year-old male KT recipient with a diagnosis of squamous cell carcinoma presenting with acute kidney injury 2 weeks following initiation of an ICI., Diagnoses: Both patients were diagnosed with acute rejection in the setting of reduced immunosuppression and initiation of an ICI., Interventions: Both cases received an increased dose of steroid without improvement of graft function. The first patient subsequently underwent a delayed graft nephrectomy due to complications of acute rejection, whereas the second patient did not undergo nephrectomy., Outcomes: The first patient experienced complications including perioperative bleeding requiring multiple operations, but ultimately stabilized on hemodialysis and showed a durable response to ICI. The second patient remained dialysis-dependent post-ICI treatment and was readmitted with allograft complications leading to his eventual death., Teaching Points: This study underscores the complexity of managing KT recipients diagnosed with malignancy and receiving ICIs. The balance between immunosuppression reduction to treat malignancy and preventing allograft rejection presents a significant challenge. Key considerations include the risk of acute allograft rejection and patient-centered decision-making. These cases highlight the need for further research to develop evidence-based guidelines for managing this patient population. In addition, the patient perspective in this study highlights the importance of careful risk-benefit analysis and the impact of treatment decisions on patient-focused outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Solid organ transplant recipients (SOTR) are at increased risk from COVID-19. Over time, the absolute risk of adverse outcomes after COVID-19 has decreased in both the non-immunosuppressed/immunocompromised (non-ISC) general population, and amongst SOTR. Using the N3C, we examined the absolute risk of mortality, major adverse renal or cardiac events, and hospitalization after COVID-19 diagnosis amongst non-ISC and SOTR populations over five waves of the pandemic (Wave 1: Ancestral COVID; Wave 2: Alpha; Wave 3: Delta; Wave 4: Omicron; Wave 5: Omicron). Within each wave, we determined the relative risk of each outcome for SOTR versus the non-ISC population based on crude event rates, and then used multivariable cox proportional hazards models and logistic regression to determine the adjusted risk of each outcome based on SOT status. Throughout the pandemic, including during the Omicron wave (Wave 5), SOTR were at greater absolute risk for each outcome than non-ISC patients ( p -values all <0.001). The adjusted risk of SOT status for each outcome was relatively stable over time (aHR 1.28-1.61 for mortality; aHR 1.31-1.47 for MACE; aHR 1.72-1.90 for MARCE; aHR 1.75-2.07 for AKI; and aOR 1.53-1.81 for hospitalization). Despite a reduction in the absolute risk of COVID-19 complications, the relative risk for SOTR versus the non-ISC population has not improved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Vinson, Anzalone, Schissel, Dai, Agarwal, Lee, Olex and Mannon.)

Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (P value < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management., Objective: To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era., Methods: Design: Retrospective population-based cohort study., Setting: Ontario, Canada., Participants: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017., Exposure: Sex (female vs. male)., Outcomes and Measures: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression., Results: Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99-1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83-1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96-0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994-0.997])., Conclusions: Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension., Methods: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities., Results: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P <0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P <0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P <0.001)., Conclusions: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group., Competing Interests: Disclosures A.J. Vinson has accepted consultancy funding from Paladin Labs, Inc, and Takeda Pharmaceuticals. The other authors report no conflicts.

Background: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female vs male heart transplant recipients., Methods: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988-2019, and subsequently combined using 2-stage individual patient data meta-analysis, to compare the excess risk of mortality in female vs male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age., Results: We analyzed 108,918 patients. When the donor was male, female recipients 0-12 years (Relative excess risk (RER) 1.13, 95% CI 1.00-1.26), 13-44 years (RER 1.17, 95% CI 1.10-1.25), and ≥45 years (RER 1.14, 95% CI 1.02-1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13-44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00-1.20), though not significantly (p = 0.05)., Conclusions: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown., Methods: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age., Results: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity., Conclusions: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss., Competing Interests: A.J.V. has accepted consulting fees and fellowship grant funding from Paladin Labs Inc. A.M. is supported by grants from the German Research Foundation (DFG; ME 3696/5-1 and ME3696/3-1) and the Lower Saxony Ministry of Science and Culture. C.S. is supported by the European Union’s Horizon 2020 Research and Innovation Programme (grant 952512). G.W. is supported by National Health and Medical Research Council Investigator (APP 1195414) and Career Development Fellowship (APP 1147657). R.S.-P. is supported by a Fonds de recherche du Quebec—Santé chercheur boursier clinician award (grant 254386) and Canadian Institutes of Health Research (grant FRN-156730). The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: In the United States, women are less likely to be referred, activated on the waitlist, or undergo kidney transplant (KT) than men; contemporary Canadian data regarding access to transplant for women are lacking., Methods: Among patients initiating dialysis in Nova Scotia (NS), Canada from 2010 to 2020, we examined the association of candidate gender with overall access to KT, including the following: (i) odds of transplant referral within 1 year of dialysis initiation, (ii) odds of activation on the transplant waitlist (if referred), and (iii) time-to-transplantation (if activated) using logistic regression or Cox proportional hazards models as appropriate., Results: Among 749 patients deemed potentially eligible for transplant, women had lower transplant rates than men (adjusted hazard ratio [aHR]: 0.53, 95% confidence interval [CI]: 0.36-0.78); this was amplified among patients aged >60 years (aHR: 0.25, 95% CI: 0.09-0.69). Compared with men, women had a lower adjusted odds of transplant referral (adjusted odds ratio [aOR]: 0.57, 95% CI: 0.35-0.93) by 1 year after dialysis initiation. Among those referred, women had lower odds of waitlist activation than men (aOR: 0.58, 95% CI: 0.30-1.11); and among those activated, women had lower hazard of KT (aHR: 0.74, 95% CI: 0.51-1.09), though these differences were not statistically significant. Women in NS experience lower overall access to transplant, including less referral, activation and KT compared with men., Conclusion: Gender-based barriers to any of (or in this case each of) referral, activation, or transplantation result in inequities in access; identification of disparities at these critical decision points is an important first step toward ensuring equal access for all., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Women are underrepresented in the leadership of and participation in randomized controlled trials (RCTs). We conducted a bibliometric review of nephrology RCTs to examine trial leadership by women and participation of women in nephrology RCTs., Methods: A bibliometric review of RCTs published in top medical, surgical, or nephrology journals was conducted using MEDLINE and EMBASE from January 2011 to December 2021. Leadership by women as corresponding authors, women trial participation, and trial characteristics were examined with duplicate independent data extraction. Logistic regression was used to examine associations between trial characteristics and women leadership and trial participation., Results: A total of 1770 studies were screened and 395 RCTs met eligibility criteria. The number (%) of women in corresponding, first, and last authorship positions were as follows: 89 (22%), 109 (28%), and 74 (19%), respectively, without change over time ( P  = 0.94). The median percentage (interquartile range [IQR]) of women trial participants was 39.0% (13.5%) with no difference between women or men lead authors ( P  = 0.15). Men lead authors were statistically less likely to enroll women in RCTs. Women lead authors were less likely to be funded by industry (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.14-0.63; P  = 0.002) or lead international trials (OR: 0.11; 95% CI: 0.01-0.83; P  = 0.03). Trials with sex-specific eligibility criteria were more likely to have women leaders (OR: 2.56; 95% CI: 1.19-5.49; P  = 0.02) than those without., Discussion: Gender inequalities in RCT leadership and RCT participation exist in nephrology and did not improve over time. Strategies to improve inequalities need to be implemented and evaluated., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: The relationship between post-operative urine output (UO) following kidney transplantation and long-term graft function has not been well described., Objective: In this study, we examined the association between decreased UO on post-operative day 1 (POD1) and post-transplant outcomes., Design: This is a retrospective cohort study., Setting: Atlantic Canada., Patients: Patients from the 4 Atlantic Canadian provinces (Nova Scotia, New Brunswick, Newfoundland, and Prince Edward Island) who received a live or deceased donor kidney transplant from 2006 through 2019 through the multiorgan transplant program at the Queen Elizabeth II Health Sciences Centre (QEII) hospital in Halifax, Nova Scotia., Measurements: Using multivariable Cox proportional hazards models, we assessed the association of low POD1 UO (defined as ≤1000 mL) with death-censored graft loss (DCGL). In secondary analyses, we used adjusted logistic regression or Cox models as appropriate to assess the impact of UO on delayed graft function (DGF), prolonged length of stay (greater than the median for the entire cohort), and death., Results: Of the 991 patients included, 151 (15.2%) had a UO ≤1000 mL on POD1. Low UO was independently associated with DCGL (hazard ratio [HR] = 4.00, 95% confidence interval [CI] = 95% CI = 1.55-10.32), DGF (odds ratio [OR] = 45.25, 95% CI = 23.00-89.02), and prolonged length of stay (OR = 5.06, 95% CI = 2.95-8.69), but not death (HR = 0.81, 95% CI = 0.31-2.09)., Limitations: This was a single-center, retrospective, observational study and therefore has inherent limitations of generalizability, data collection, and residual confounding., Conclusions: Overall, reduced post-operative UO following kidney transplantation is associated with an increased risk of DCGL, DGF, and prolonged hospital length of stay., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.J.V. has received consultancy and fellowship grant funding through Paladin Labs Inc, and K.T. has received advisory board and CME support from Astra Zeneca, Baxter, Bayer, GSK, Otsuka, and Vifor Pharmaceuticals. However, the authors of this manuscript have no conflicts of interest to declare as described by the International Committee of Medical Journal Editors that are relevant to the current submission., (© The Author(s) 2024.)

Purpose of the Conference: The 2022 Banff-Canadian Society of Transplantation Meeting in Banff, Alberta, brought together transplant professionals to review new developments across various aspects of solid organ transplantation (SOT) in Canada., Sources of Information: Presentations included consensus recommendations from expert-led forums; experiences with new procedures and legislation; reports from public health data repositories; original clinical and laboratory research; and industry updates regarding novel technologies. Speakers referenced articles and reports published in peer-reviewed journals and online, and unpublished data and preliminary findings., Methods: All authors attended presentations in-person or virtually. Recordings of select presentations were available for later review. Summaries emphasize concepts indicated by speakers as new and clinically relevant., Key Findings: The COVID-19 pandemic disproportionately affected solid organ transplant recipients (SOTRs), who experience worse outcomes of COVID-19 infection than the general population. Vaccinations demonstrate an attenuated immunological response in SOTRs yet provide meaningful protection. Monoclonal antibodies are effective for both passive immunization and treatment of COVID-19 in SOTRs. Infection control protocols have driven the development of virtual methods for clinical research, such as using home blood draws and virtual follow-up to evaluate vaccine efficacy in SOTRs; and patient care delivery, such as employing telerehabilitation post transplant. Access to living kidney donation is limited by various disincentives experienced by potential donors, which may be overcome by more efficient evaluations including a One-Day Living Kidney Donor Assessment Clinic. The International Donation and Transplantation Legislative and Policy Forum provided a means of establishing consensus guidance for organ donation and transplantation (ODT) program policy to standardize delivery across jurisdictions. The implementation of a deemed consent model for organ and tissue donation in Nova Scotia may provide insight as to whether this model indeed improves access to organs. Canada's Indigenous population experiences unique barriers to transplantation, prompting efforts for more inclusive ODT policy-making. The Pan-Canadian ODT Data and Performance Reporting System Project has defined performance quality indicators, of which iTransplant and other point-of-care software solutions may facilitate collection; however, these endeavors ultimately require information technology infrastructure that exceeds the capabilities of the existing Canadian Organ Replacement Register and Canadian Transplant Registry. Pig-to-human xenotransplantation requires genetic modification of pigs and xenoantibody testing in recipients but may yet prove viable. Serum cell-free DNA, urine biomarkers, and genetic markers offer an alternative to routine biopsy for identifying subclinical rejection. Modified perfusion temperatures and perfusion solutions with hydrogen sulfide donor compounds may improve organ preservation. Molecular compatibility tools provide another means of improving SOTR outcomes, and the Genome Canada Transplant Consortium has been examining important considerations of their implementation., Limitations: We were unable to capture all presentations and topics at the meeting due to the sizable quantity and variety. Topics ultimately excluded from this summary include those in pathology including Banff Classification updates; those unique to extra-renal SOT; as well as numerous abstract and poster presentations, allied health provider forums, and business meetings. A portion of the material was presented by speakers prior to peer-review or publication., Implications: The various conference presentations summarized in this report identify methods by which individual clinicians and provincial ODT programs may improve access, delivery, and quality of SOT care in Canada, while additionally identifying gaps in the literature that investigators are encouraged to pursue., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Referral for kidney transplant (KT) is variable, with women often disadvantaged. This study aimed to better characterize Canadian transplant referral practices and identify potential differences by respondent and/or patient gender using surveys targeted at healthcare practitioners (HCPs) involved in KT., Methods: Surveys consisting of 25 complex patient cases representing 7 themes were distributed to KT HCPs across Canada (March 3, 2022-April 27, 2022) using national nephrology/transplant society email registries. Respondents were asked whether they would refer the patient for transplant. Two identical surveys were created, differing only by gender/gender pronouns used in each case. Multivariable logistic regression was used to assess the association of respondent demographics and patient themes (including case gender) with the odds of transplant referral (overall and stratifying by respondent gender)., Results: Overall, the referral rate was 58.0% among 97 survey respondents (46.4% male). Case themes associated with a lower likelihood of referral included adherence concerns (adjusted odds ratio [aOR] 0.65; 95% confidence interval [CI], 0.45-0.94), medical complexity (aOR 0.57; 95% CI, 0.38-0.85), and perceived frailty (aOR 0.63; 95% CI, 0.47-0.84). Respondent gender was not associated with differences in KT referral (aOR 0.91; 95% CI, 0.65-1.26 for male versus female respondents) but modified the association of frailty (less referral for male than female respondents, P  = 0.005) and medical complexity (less referral for female than male respondents, P  = 0.009) with referral. There were no differences in referral rate by case gender ( P  = 0.82)., Conclusions: KT referral practices vary among Canadian HCPs. In this study, there were no differences in likelihood of transplant referral by candidate gender., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation., Methods: The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF)., Results: A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT., Conclusions: Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KKT has conducted CME/Advisory board activities for Baxter, Bayer, Astra Zeneca, Outsuka, and GlaxoSmith Kline. AJV has accepted investigator-initiated fellowship grant funding and consultancy funding from Paladin Labs Inc., (© The Author(s) 2023.)

Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases. This included first deceased donor kidney transplant recipients and accounted for the modifying effects of donor sex and recipient age. After harmonization of variables across cohorts, relative survival models were fitted in each cohort separately and results were combined using individual patient data meta-analysis among 466,892 individuals (1988-2019). When the donor was male, female recipients 0-12 years (Relative Excess Risk 1.54, 95% Confidence Interval 1.20-1.99), 13-24 years (1.17, 1.01-1.34), 25-44 years (1.11, 1.05-1.18) and 60 years and older (1.05, 1.02-1.08) showed higher excess mortality risks than male recipients of the same age. When the donor was female, the Relative Excess Risk for those over 12 years were similar to those when the donor was male. There is a higher excess mortality risk in female than male recipients with differences larger at younger than older ages and only statistically significant when the donor was male. While these findings may be partly explained by the known sex differences in graft loss risks, sex differences in the risks of death with graft function may also contribute. Thus, higher risks in females than males suggest that management needs to be modified to optimize transplant outcomes among females., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown., Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19., Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023., Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19., Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting., Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF., Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.

Women are often underrepresented in clinical trials. It is unclear if this applies to trials in kidney transplant (KT) and whether the intervention or trial focus influences this. In this study, the weighted participation-to-prevalence ratio (PPR) for women enrollees in KT trials was determined for leading medical transplant or kidney journals between 2018 and 2023 using meta-regression overall and in three sensitivity analyses by: 1) Whether the intervention involved immunosuppression; 2) Area of trial focus; rejection, cardiometabolic, infection, lifestyle, surgical; 3) Whether the intervention was medical/surgical or social/behavioral. Overall, 33.7% of participants in 24 trials were women. The overall pooled PPR for the included trials was 0.80, 95% CI 0.76-0.85, with significant heterogeneity between trials ( I 2 56.6%, p-value < 0.001). Women had a lower PPR when the trial involved immunosuppression (PPR 0.77, 95% CI 0.72-0.82) than when it did not (PPR 0.86, 95% CI 0.80-0.94) and were less likely to participate in trials with a medical/surgical versus behavioral intervention; the lowest PPR for women was in studies examining rejection risk (PPR 0.75, 95% CI 0.70-0.81). There is better representation of women in KT trials compared to other medical disciplines, however women remain underrepresented in transplant trials examining immunosuppression and rejection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vinson and Ahmed.)

Background: Significant variability in organ acceptance thresholds have been demonstrated across the United States, but data regarding the rate and rationale for kidney donor organ decline in Canada are lacking., Objective: To examine decision making regarding deceased kidney donor acceptance and non-acceptance in a population of Canadian transplant professionals., Design: A survey study of theoretical deceased donor kidney cases of increasing complexity., Setting: Canadian transplant nephrologists, urologists, and surgeons making donor call decisions responding to an electronic survey between July 22 and October 4, 2022., Participants: Invitations to participate were distributed to 179 Canadian transplant nephrologists, surgeons, and urologists through e-mail. Participants were identified by contacting each transplant program and requesting a list of physicians who take donor call., Measurements: Survey respondents were asked whether they would accept or decline a given donor, assuming there was a suitable recipient. They were also asked to cite reasons for donor non-acceptance., Methods: Donor scenario-specific acceptance rates (total acceptance divided by total number of respondents for a given scenario and overall) and reasons for decline were determined and presented as a percentage of the total cases declined., Results: In all, 72 respondents from 7 provinces completed at least one question of the survey, with considerable variability between acceptance rates for centers; the most conservative center declined 60.9% of donor cases, whereas the most aggressive center declined only 28.1%, P -value < .001. There was an increased risk of non-acceptance with advancing age, donation after cardiac death, acute kidney injury, chronic kidney disease, and comorbidities., Limitations: As with any survey, there is the potential for participation bias. In addition, this study examines donor characteristics in isolation, however, asks respondent to assume there is a suitable candidate available. In reality, whenever donor quality is considered, it should be considered in the context of the intended recipient., Conclusion: In a survey of increasingly medically complex deceased kidney donor cases, there was significant variability in donor decline among Canadian transplant specialists. Given relatively high rates of donor decline and apparent heterogeneity in acceptance decisions, Canadian transplant specialists may benefit from additional education regarding the benefits achieved from even medically complex kidney donors for appropriate candidates relative to remaining on dialysis on the transplant waitlist., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Patients receiving maintenance hemodialysis frequently require ambulance transport to the emergency department (ambulance-ED transport). Identifying predictors of outcomes after ambulance-ED transport, especially the need for timely dialysis, is important to health care providers., Objective: The purpose of this study was to derive a risk-prediction model for urgent dialysis after ambulance-ED transport., Design: Observational cohort study., Setting and Patients: All ambulance-ED transports among incident and prevalent patients receiving maintenance hemodialysis affiliated with a regional dialysis program (catchment area of approximately 750 000 individuals) from 2014 to 2018., Measurements: Patients' vital signs (systolic blood pressure, oxygen saturation, respiratory rate, and heart rate) at the time of paramedic transport and time since last dialysis were utilized as predictors for the outcome of interest. The primary outcome was urgent dialysis (defined as dialysis in a monitored setting within 24 hours of ED arrival or dialysis within 24 hours with the first ED patient blood potassium level >6.5 mmol/L) for an unscheduled indication. Secondary outcomes included, hospitalization, hospital length of stay, and in-hospital mortality., Methods: A logistic regression model to predict outcomes of urgent dialysis. Discrimination and calibration were assessed using the C-statistic and Hosmer-Lemeshow test., Results: Among 878 ED visits, 63 (7.2%) required urgent dialysis. Hypoxemia (odds ratio [OR]: 4.04, 95% confidence interval [CI]: 1.75-9.33) and time from last dialysis of 24 to 48 hours (OR: 3.43, 95% CI: 1.05-11.9) and >48 hours (OR: 9.22, 95% CI: 3.37-25.23) were strongly associated with urgent dialysis. A risk-prediction model incorporating patients' vital signs and time from last dialysis had good discrimination (C-statistic 0.8217) and calibration (Hosmer-Lemeshow goodness of fit P value .8899). Urgent dialysis patients were more likely to be hospitalized (63% vs 34%), but there were no differences in inpatient mortality or length of stay., Limitations: Missing data, requires external validation., Conclusion: We derived a risk-prediction model for urgent dialysis that may better guide appropriate transport and care for patients requiring ambulance-ED transport., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality., Methods: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period., Results: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures., Conclusions: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Anzalone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clinical outcomes in solid organ transplant (SOT) recipients with breakthrough COVID (BTCo) after two doses of mRNA vaccination compared to the non-immunocompromised/immunosuppressed (ISC) general population, are not well described. In a cohort of adult patients testing positive for COVID-19 between December 10, 2020 and April 4, 2022, we compared the cumulative incidence of BTCo in a non-ISC population to SOT recipients (overall and by organ type) using the National COVID Cohort Collaborative (N3C) including data from 36 sites across the United States. We assessed the risk of complications post-BTCo in vaccinated SOT recipients versus SOT with unconfirmed vaccination status (UVS) using multivariable Cox proportional hazards and logistic regression. BTCo occurred in 4776 vaccinated SOT recipients over a median of 149 days (IQR 99-233), with the highest cumulative incidence in heart recipients. The relative risk of BTCo was greatest in SOT recipients (relative to non-ISC) during the pre-Delta period (HR 2.35, 95% CI 1.80-3.08). The greatest relative benefit with vaccination for both non-ISC and SOT cohorts was in BTCo mortality (HR 0.37, 95% CI 0.36-0.39 for non-ISC; HR 0.67, 95% 0.57-0.78 for SOT relative to UVS). While the relative benefit of vaccine was less in SOT than non-ISC, SOT patients still exhibited significant benefit with vaccination., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: As the prevalence of obesity increases globally, appreciating the effect of donor and recipient (DR) obesity on graft outcomes is of increasing importance. Methods: In a cohort of adult, kidney transplant recipients (2000-2017) identified using the SRTR, we used Cox proportional hazards models to examine the association between DR obesity pairing (body mass index (BMI) >30 kg/m 2 ), and death-censored graft loss (DCGL) or all-cause graft loss, and logistic regression to examine risk of delayed graft function (DGF) and ≤30 days graft loss. We also explored the association of DR weight mismatch (>30 kg, 10-30 kg (D>R; D

Background: Sex differences in kidney graft loss rates were reported in the United States. Whether these differences are present in other countries is unknown., Methods: We estimated the association between recipient sex and death-censored graft loss in patients of all ages recorded in the Scientific Registry of Transplant Recipients, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study registries who received a first deceased donor kidney transplant (1988-2019). We used multivariable Cox regression models, accounting for the modifying effects of donor sex and recipient age, in each registry separately; results were combined using individual patient data meta-analysis., Results: We analyzed 438 585 patients. Young female patients 13-24 y old had the highest crude graft loss rates (female donor: 5.66; male donor: 5.50 per 100 person-years). Among young recipients of male donors, females showed higher graft loss risks than males (0-12 y: adjusted hazard ratio [aHR] 1.42, (95% confidence interval [CI], 1.17-1.73); 13-24 y: 1.24 (1.17-1.32); 25-44 y: 1.09 (1.06-1.13)). When the donor was female, there were no significant differences by recipient sex among those of age <45 y; however, the aHR for females was 0.93 (0.89-0.98) in 45-59 y-old and 0.89 (0.86-0.93) in ≥ 60 y-old recipients. Findings were similar for all 3 registries in most age intervals; statistically significant heterogeneity was seen only among 13-24-y-old recipients of a female donor (I2 = 71.5%, P = 0.03)., Conclusions: There is an association between recipient sex and kidney transplantation survival that is modified by recipient age and donor sex., Competing Interests: A.J.V. has accepted consulting fees and fellowship grant funding from Paladin Labs Inc. A.M. is supported by grants from the German Research Foundation (DFG; ME 3696/5-1 and ME3696/3-1) and the Lower Saxony Ministry of Science and Culture. G.W. is supported by NHMRC Investigator (APP 1195414) and Career Development Fellowship (APP 1147657). R.S.-P. is supported by a Fonds de recherche du Quebec—Santé chercheur boursier clinician award (grant no. 254386) and CIHR (grant FRN-156730). This study was supported by funding from the Canadian Institutes of Health Research PJT-165832. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Preemptive kidney transplantation is the preferred treatment for end-stage kidney disease. However, deceased donor (DD) kidneys are limited, and the net benefit of allocating kidneys to a preemptively waitlisted patient rather than to a patient receiving dialysis is unclear., Objective: To estimate the net benefit and costs of allocating kidneys to preemptively waitlisted patients vs those receiving dialysis., Design, Setting, and Participants: This medical decision analytical model used data from the 2020 US Renal Data System to calculate patient survival among waitlisted patients who received a DD kidney transplant. Four patients were simulated, with similar characteristics: (1) a patient on the preemptive waiting list receiving a DD transplant, (2) a patient on the preemptive waiting list never receiving a transplant, (3) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) receiving a transplant, and (4) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) never receiving a transplant. Annual probability of initiating dialysis (for patients 1 and 2) and duration of dialysis (for patients 3 and 4) were varied in sensitivity analyses., Exposures: Allocating a DD kidney to a patient on the preemptive waiting list vs the same kidney to a patient receiving dialysis for less than 1 year, with similar recipient characteristics., Main Outcomes and Measures: Differences in projected quality-adjusted life-years (QALYs) and total costs., Results: In a simulated patient with a mean start age of 50 years (range, 30-64 years), the patient receiving a preemptive DD transplantation experienced 10.58 (95% CI, 10.36-10.80) QALYs, and the patient on the preemptive waiting list never transplanted experienced 6.83 (95% CI, 6.67-6.99) QALYs. The patient receiving DD transplantation after less than 1 year of dialysis experienced 10.33 (95% CI, 10.21-10.55) QALYs, and the patient receiving dialysis who remained on the waiting list experienced 6.20 (95% CI, 6.04-6.36) QALYs; allocating a DD kidney to the preemptive patient added 3.75 (95% CI, 3.57-3.93) QALYs, whereas allocating the kidney to the patient already receiving dialysis added 4.13 (95% CI, 3.92-4.31) QALYs. While the estimated posttransplant survival was longest for the preemptive transplant recipient, preferentially allocating the kidney to the preemptive patient results in 0.39 (95% CI, 0.49-0.29) fewer QALYs. The net cost of preemptive transplantation was $54 100 (95% CI, $44 100-$64 100) more than transplantation to a waitlisted patient. If the rate of transitioning to dialysis was 20 (rather than 33) events per 100 patient waiting list-years, the net QALYs were -0.67 (95% CI, -0.78 to -0.56). If the patient was receiving dialysis for 3 to 4 years (vs <1 year) the net benefit was not significantly different; however, net costs were considerably higher for the preemptive option., Conclusions and Relevance: In this decision analytic model study, although allocating DD kidneys to patients preemptively was the best option from a patient perspective, allocating DD kidneys to patients receiving dialysis was a better use of a scare resource from a societal perspective.

Background: Post-transplant diabetes mellitus (PTDM) is an important complication after kidney transplantation that results in reduced patient and allograft survival. Although there are established risk factors for PTDM, whether pretransplant C-peptide levels associate with PTDM is unknown. Therefore, in this study, we aimed to examine the association of pretransplant C-peptide levels with PTDM., Methods: This was a cohort study of nondiabetic adult patients who underwent kidney transplant in Nova Scotia, Canada, between January 1, 2016, and March 31, 2021, with fasting C-peptide levels measured before transplant. Multivariable logistic regression was used to determine the association of pretransplant C-peptide (dichotomized around the median) with PTDM at 1 year post transplant. Given the known association between pretransplant obesity and PTDM, we repeated our primary analysis in a cohort restricted to a BMI of 20-35 kg/m 2 ., Results: The median C-peptide value was 3251 (Q1 2480, Q3 4724); pretransplant C-peptide level was dichotomized at 3000 pmol/L. PTDM occurred in 25 (19%) individuals. Thirty percent of patients in the high and only 2% of patients in the low C-peptide groups developed PTDM ( P <0.001). A C-peptide level ≥3000 pmol/L was strongly associated with PTDM in multivariable analysis (OR=18.9, 95% CI, 2.06 to 174.2). In a restricted cohort with a BMI of 20-35 kg/m 2 , an elevated pretransplant C-peptide remained independently associated with the risk of PTDM (OR=15.7, 95% CI, 1.64 to 150.3). C-peptide was the only factor independently associated with PTDM in this restricted BMI cohort., Conclusions: A pretransplant C-peptide level ≥3000 pmol/L was associated with a nearly 20-fold increased odds of PTDM at 1 year post kidney transplantation. Identifying patients with high pretransplant C-peptide levels may therefore help identify those at risk for PTDM who may benefit from focused preventative and therapeutic interventions and support., Competing Interests: L. Gunaratnam reports consultancy for AstraZeneca Canada, Inc., Novartis Canada Inc., and Paladin Labs, Inc.; honoraria from AstraZeneca Canada, Inc., Novartis Canada Inc., and Paladin Labs Inc.; an advisory or leadership role for AstraZeneca Canada, Inc., Bayer, Inc., and Paladin Labs, Inc.; and participation in a speakers’ bureau for AstraZeneca Canada, Inc. K.K. Tennankore reports consultancy for AstraZeneca, Bayer, GSK, Otsuka, and Vifor; research funding from Otsuka Canada; honoraria from Astra Zeneca, Baxter, GSK, and Otsuka; an advisory or leadership role for the Canadian Journal of Kidney Health and Disease (associate editor); and participating in a speakers’ bureau for AstraZeneca, Baxter, and Bayer. A.J. Vinson reports consultancy for Paladin Labs, Inc., and research funding from Paladin Labs, Inc. K. West reports consultancy for Envarsus Canada, and honoraria from Envarsus Canada. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background: Hyperkalemia is common among patients on maintenance hemodialysis (HD) and is associated with mortality. We hypothesized that clinical characteristics available at time of paramedic assessment before emergency department (ED) ambulance transport (ambulance-ED) would associate with severe hyperkalemia (K≥6 mmol/L). Rapid identification of patients who are at risk for hyperkalemia and thereby hyperkalemia-associated complications may allow paramedics to intervene in a timely fashion, including directing emergency transport to dialysis-capable facilities., Methods: Patients on maintenance HD from a single paramedic provider region, who had at least one ambulance-ED and subsequent ED potassium from 2014 to 2018, were examined using multivariable logistic regression to create risk prediction models inclusive of prehospital vital signs, days from last dialysis, and the presence of prehospital electrocardiogram (ECG) features of hyperkalemia. We used bootstrapping with replacement to validate each model internally, and performance was assessed by discrimination and calibration., Results: Among 704 ambulance-ED visits, severe hyperkalemia occurred in 75 (11%); 26 patients with ED hyperkalemia did not have a prehospital ECG. Younger age at transport, longer HD vintage, more days from last hemodialysis session (OR=49.84; 95% CI, 7.72 to 321.77 for ≥3 days versus HD the same day [before] ED transport), and prehospital ECG changes (OR=6.64; 95% CI, 2.31 to 19.12) were independently associated with severe ED hyperkalemia. A model incorporating these factors had good discrimination (c-statistic 0.82; 95% CI, 0.76 to 0.89) and, using a cutoff of 25% probability, correctly classified patients 89% of the time., Conclusions: Characteristics available at the time of ambulance-ED were associated with severe ED hyperkalemia. An awareness of these associations may allow health care providers to define novel care pathways to ensure timely diagnosis and management of hyperkalemia., Competing Interests: D.A. Clark reports research funding from Otsuka Canada Pharmaceutical, Inc., and honoraria from Baxter Canada. P.T. Fok reports ownership interest in Merck Pharmaceuticals and Moderna, Inc., but is no longer holding stocks of either company, and is on the Board of Directors of the Canadian Association of Emergency Physicians but receives no compensation for this. K.K. Tennankore reports consultancy for AstraZeneca, Baxter, Bayer, and Otsuka; research funding from Otsuka Canada; honoraria from Astra Zeneca, Baxter, Bayer, and Otsuka; being associate editor for the Canadian Journal of Kidney Health and Disease; and participating in a speakers’ bureau for AstraZeneca, Baxter, and Bayer. A.J. Vinson reports consultancy for Paladin Labs, Inc., and research funding from Paladin Labs, Inc. H. Wiemer reports research funding from Purdue Pharma (Canada). All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

While older males are at the highest risk for poor coronavirus disease 2019 (COVID-19) outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (January 1, 2020-June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID-19 diagnosis in those with and without SOT. We examined the exposure of age-stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3996 (36.4%) SOT and 91 646 (4.8%) non-SOT patients developed MARCE. Risk of post-COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non-SOT cohort (HR 0.89, 95% CI 0.81-0.98 for SOT and HR 0.61, 95% CI 0.60-0.62 for non-SOT [females vs. males]). This represents the largest COVID-19 SOT cohort to date and the first-time sex-age-stratified and allograft-specific COVID-19 outcomes have been explored in those with SOT., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Competing Interests: The authors declare no funding or conflicts of interest.

Background: The need for repeat transplant due to failing kidney allografts is increasing over time. The benefit of preemptive kidney retransplant (PKre-T) is controversial. Marginalized populations are less likely to undergo their first transplant preemptively; however, whether inequities exist for those undergoing PKre-T is unknown., Methods: We performed a cohort study of adult patients undergoing live and deceased kidney transplant in the United States from 2000 to 2018 identified using the Scientific Registry of Transplant Recipients, and we identified patients with first preemptive kidney transplant (PKT) and PKre-T. In the primary analysis, a multivariable logistic regression was used to identify independent predictors of PKre-T. In secondary analyses, multivariable Cox models were used to determine the association of PKre-T with death-censored and all-cause graft loss., Results: In total, 4910 (15.5%) patients underwent PKre-T, and 43,293 (19.1%) underwent first PKT. Inequities in access to PKre-T persisted (OR, 0.49; 95% CI, 0.44 to 0.55 for unemployed versus full time; OR, 1.61; 95% CI, 1.14 to 2.25 for graduate school versus not completing high school; OR, 0.61; 95% CI, 0.52 to 0.70 for Black versus White race); 7.1% of all transplanted Black patients received PKre-T versus 17.4% of White patients. Women were more likely to undergo PKre-T than men (OR, 1.42; 95% CI, 1.29 to 1.57). PKre-T was associated with superior graft survival relative to retransplant after a period of dialysis (HR, 0.73; 95% CI, 0.67 to 0.80 for all-cause graft failure; HR, 0.72; 95% CI, 0.65 to 0.81 for death-censored graft loss)., Conclusions: Despite improved patient and graft survival, inequities in access to PKre-T persist. Patients with lower education, patients with reduced employment status, patients of Black race, and men are less likely to receive PKre-T., Competing Interests: B.J. Foster reports research funding as a coinvestigator from two grants sponsored by Astellas Canada. R.B. Mannon reports research funding from Astellas, CareDx, CSL Behring, Mallinckrodt, Quark Pharmaceuticals, and Transplant Genomics, Inc.; honoraria from CSL Behring, Hansa, Novartis, Sanofi, and Vitaerris; scientific advisor or membership with the steering committee of the Vitaeris VKTX01 Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients (IMAGINE) Trial; and other interests/relationships as the chair of Data Safety Monitoring Board for the National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, member of the American Society of Nephrology (ASN) Grants Committee, chair of the ASN Policy and Advocacy Committee, chair of Women in Transplantation, member of the Program Committee TTS 2020 and 2022, and cochair of the SRTR Review Committee. K.K. Tennankore reports consultancy agreements with AstraZeneca, Baxter, Bayer, Janssen, and Otsuka; research funding from Astellas Canada and Otsuka Canada; honoraria from Astra Zeneca, Bayer, and Otsuka; scientific advisor or membership as an associate editor of the Canadian Journal of Kidney Health and Disease; and speakers bureau for AstraZeneca, Baxter, and Bayer. A.J. Vinson reports consultancy agreements with Paladin Labs Inc. and research funding from Paladin Labs Inc. K. West reports consultancy agreements with Envarsus Canada and honoraria from Envarsus Canada. The remaining author has nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant (SOT) recipients. The National COVID Cohort Collaborative was developed to facilitate analysis of patient-level data for those tested for COVID-19 across the United States., Methods: In this study, we identified a cohort of SOT recipients testing positive or negative for COVID-19 (COVID+ and COVID-, respectively) between January 1, 2020, and November 20, 2020. Univariable and multivariable logistic regression were used to determine predictors of a positive result among those tested. Outcomes following COVID-19 diagnosis were also explored., Results: Of 18 121 SOT patients tested, 1925 were positive (10.6%). COVID+ SOT patients were more likely to have a kidney transplant and be non-White race. Comorbidities were common in all SOT patients but significantly more common in those who were COVID+. Of COVID+ SOT, 42.9% required hospital admission. COVID+ status was the strongest predictor of acute kidney injury (AKI), rejection, and graft failure in the 90 d after testing. A total of 40.9% of COVID+ SOT experienced a major adverse renal or cardiac event, 16.3% experienced a major adverse cardiac event, 35.3% experienced AKI, and 1.5% experienced graft loss., Conclusions: In the largest US cohort of COVID+ SOT recipients to date, we identified patient factors associated with the diagnosis of COVID-19 and outcomes following infection, including a high incidence of major adverse renal or cardiac event and AKI., Competing Interests: A.J.V. has done consultancy work and received funding for a fellowship project grant through Paladin Labs Inc. G.A. has received educational funds from Mallinckrodt Pharmaceuticals and has served as principal investigator for studies by Mallinckrodt Pharmaceuticals and CSL Behring. R.B.M. reports grants from Mallinckrodt, Care Dx, CSL Behring, Transplant Genomics, Astellas, and Quark Pharmaceuticals; personal fees from Vitaerris as member of the IMAGINE Trial Steering committee; personal fees from Novartis, Sanofi, and Hansa; and personal fees from American Journal of Transplantation as Deputy Editor of the journal, outside the submitted work. The other authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Strategic organ allocation is expected to prolong patient and graft survival after transplant. This study explored differences in graft survival when kidneys are allocated based on strategic donor-recipient (D-R) pairing vs with the existing Kidney Allocation System (KAS)., Methods: Using the Scientific Registry of Transplant Recipients from 2000 to 2014, we used a multivariable Cox model to assess the hazard ratios (HRs) for death or graft failure among 3 hypothetical donor kidneys transplanted into 3 hypothetical recipients, relative to an ideally matched D-R pair. Median predicted survival for each of the 9 possible D-R pairing combinations was determined, and outcomes for strategic D-R pairing were compared with those obtained using the KAS for allocation., Results: A total of 31,607 patients (29.7%) died or developed graft loss over the study period. Strategic allocation of kidneys resulted in HRs for graft loss of 1.74 (95% confidence interval [CI], 1.41-2.14), 1.82 (95% CI, 1.46-2.26), and 1.74 (95% CI 1.38-2.19) for recipients 1, 2 and 3 respectively, whereas by following the KAS, HRs were 1.93 (95%, CI 1.63-2.28), 2.06 (95% CI, 1.74-2.44), and 1.93 (95% CI, 1.58-2.37); corresponding to 3.84, 11.39, and 7.40 months longer predicted patient or graft survival for recipients 1, 2 and 3 with strategic D-R pairing compared with the KAS., Conclusions: Allocation of kidneys by strategic D-R pairing may improve graft survival relative to allocation using the KAS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Kidney transplantation is the optimal treatment for an individual requiring kidney replacement therapy, resulting in improved survival and quality of life while costing the health care system less than maintenance dialysis. Achieving and maintaining a kidney transplant requires extensive coordination of several different health care services. To improve the quality of kidney transplant care, quality metrics or indicators that encompass all aspects of the individual's journey to transplant should be measured in a standardized fashion., Objective: To identify, categorize, and evaluate strengths and weaknesses of kidney transplant quality indicators currently being used across Canada., Design: An environmental scan of quality indicators being used by kidney organizations and programs., Setting: A 16-member volunteer pan-Canadian panel with expertise in nephrology, transplant, and quality improvement., Sample: Transplant programs, as well as provincial transplant and kidney agencies across Canada., Methods: Indicators were first categorized based on the period of transplant care and then using the Institute of Medicine and Donabedian frameworks. A 4-member subcommittee rated each indicator using a modified version of the Delphi consensus technique based on the American College of Physician/Agency for Healthcare Research and Quality criteria. Consensus ratings were subsequently shared with the entire 16-member panel for additional comments., Results: We identified 46 measures related to transplant care across 7 Canadian provinces (9 referral and evaluation, 9 waitlist activity and outcomes, 6 hospitalization for transplant surgery, 12 posttransplant care, 6 organ utilization, 4 living donor). We rated 24 indicators (52%) as necessary to distinguish high-quality from low-quality care, most of which measured effective (n = 10) or efficient (n = 6) care. Only 7 (15%) of 46 indicators evaluated person-centered or equitable care. Fourteen common indicators were measured by 5 of 7 provinces, 10 of which were deemed "necessary," measuring safe (n = 2), effective (n = 5), efficient (n = 2), and equitable (n = 1) care., Limitations: The panel lacked patient and allied health representation., Conclusions: There are a large number of kidney transplant quality indicators currently being used in Canada, some of which are common across provinces and focus primarily on measuring effective care. Person-centered and equitable care indicators were lacking, and only half of these indicators were deemed "necessary" for quality improvement. Our results should complement ongoing work to achieve national consensus on the standardization of quality indicators in kidney transplantation., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.G. has participated in consultancy for Paladin Labs Inc. A.V. has participated in advisory boards/consultancy work for Paladin Labs Inc. S.A.S. has received speaking fees from Sanofi and Baxter Canada. S.Y. has no conflicts of interest relevant to this study. All authors approved the final version of the submitted manuscript. We certify that this manuscript nor one with substantially similar content has been published or is being considered for publication elsewhere., (© The Author(s) 2021.)

Background: Live donor (LD) kidney transplantation is the best option for patients with end-stage kidney disease (ESKD). However, this may not be the best option if a patient's donor is older and considerably smaller in weight. Patient (A) with a less than ideal donor (Donor A) might enter into a live donor paired exchange (LDPE) program with the hopes of swapping for a better-quality organ. A second patient (B) who is in the LDPE may or may not benefit from this exchange with Donor A., Methods: This medical decision analysis examines the conditions that favor Patient A entering into the LDPE compared to directly accepting a kidney from their intended donor, as well as the circumstances where Patient B also benefits by accepting a lower-quality organ., Results: Under select circumstances, a paired exchange could benefit both Patients A and B. For example, a 30-year-old Patient A with a lower-quality donor might gain 1.20 1.52 1.84 quality adjusted life years (QALYs) by entering into a LDPE for a better-quality kidney, whereas a 60-year-old Patient B might gain 0.93 1.03 1.13 QALYs by accepting Donor A's kidney rather than waiting longer in the LDPE. The net benefit (or loss) of entering the LDPE differs by recipient age, donor organ quality, likelihood of Patient B being transplanted in LDPE, and likelihood of Patient A finding an ideal donor in the LDPE., Conclusion: This study shows there are ways to increase live donor utilization and effectiveness that require further research and potentially changes to the LDPE process., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

A number of studies have compared relative survival for home hemodialysis patients (including longer hours/more frequent schedules) and other forms of renal replacement therapy. While informative, many of these studies have been limited by issues pertaining to their observational design including selection bias and residual confounding. Furthermore the few randomized controlled trials that have been conducted have been underpowered to detect a survival difference. Finally, in the face of a growing recognition of the value of patient-important outcomes beyond survival, the focus of comparisons between dialysis modalities may be changing. In this review, we will discuss the determinants of survival for patients receiving home hemodialysis and address the various studies that have compared relative survival for differing home hemodialysis schedules to each of in-center hemodialysis, peritoneal dialysis and transplantation. We will conclude this review by discussing whether there is an ongoing role for survival analyses in home hemodialysis., (Copyright © 2020 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Background: Pandemics greatly interfere with overall health care delivery as resources are diverted to combat the crisis. Kidney transplantation programs were closed temporarily during the COVID-19 pandemic. Given the critical shortage of organs, their short shelf life, and their overall importance to improving length and quality of life for those with kidney disease, this analysis examines the impact of discarding deceased donor organs., Methods: The net benefit (or harm) of discarding deceased donor organs was measured in projected life years from a societal and individual perspective using a Markov model. A wide range of infection rates, pandemic durations, and case fatality rates associated with infection in wait listed and transplant recipients were examined., Results: Overall, patient life expectancy fell for both wait listed and transplant recipients as the pandemic conditions became more unfavorable. However, the overall net benefit of a transplant during the pandemic was preserved. For example, prior to the pandemic, the net benefit of a kidney transplant over dialysis was calculated to be 6.25 life years (LYs) or 8.24 quality-adjusted life years (QALYs) in a 40-year old recipient. This fell to 5.86 LYs (7.78 QALYs) during the pandemic. Even assuming plausible but higher relative case fatality rates and risks of nosocomial and donor transmission in transplant recipients compared to wait listed patients, the net benefit remained >4 years for most deceased donor organs., Conclusion: As long as hospitals have adequate resources to deal with the pandemic and can limit nosocomial infection, kidney transplantation should not be curtailed., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Worsening socioeconomic conditions in rural America have been fueling increases in chronic disease and poor health. The goal of this study was to identify cost-effective methods of deploying geographically targeted health surveys in rural areas, which often have limited resources. These health surveys were administered in New York's rural Sullivan County, which has some of the poorest health outcomes in the entire state., Methods: Comparisons were made for response rates, estimated costs, respondent demographics, and prevalence estimates of a brief health survey delivered by mail and phone using address-based sampling, and in-person using convenience sampling at a sub-county level in New York's rural Sullivan County during 2017., Results: Overall response rates were 27.0% by mail, 8.2% by phone, and 71.4% for convenience in-person surveys. Costs to perform phone surveys were substantially higher than mailed or convenience in-person surveys. All modalities had lower proportions of Hispanic respondents compared to Census estimates. Unadjusted and age-adjusted prevalence estimates were similar between mailed and in-person surveys, but not for phone surveys., Conclusions: These findings are consistent with declining response rates of phone surveys, which obtained an inadequate sample of rural residents. Though in-person surveys had higher response rates, convenience sampling failed to obtain a geographically distributed sample of rural residents. Of modalities tested, mailed surveys provided the best opportunity to perform geographically targeted rural health surveillance.

Background: Dialysis patients are frequently transported to the emergency department (ED) by Emergency Medical Services (EMS) due to acute and severe illness. However, little is known about predictors of first and recurrent transport to the ED (EMS-ED), based on characteristics at the time of dialysis initiation. Methods: We analyzed a cohort of adult (≥18 years) patients affiliated with a large quaternary care center who initiated chronic dialysis from 2009 to 2013 (last follow-up: 2015). Data on patient characteristics at the time of dialysis initiation were linked to regional EMS data. Candidate predictors of first and recurrent EMS-ED transport included comorbid conditions, dialysis characteristics and frailty severity (using the first version of the clinical frailty scale score; CFS). Time to first EMS-ED was analyzed using a multivariable sub-hazards regression model accounting for competing events (transplantation or death). Time to recurrent EMS-ED was analyzed using the Anderson-Gill counting approach, accounting for competing risks. Results: A total of 455 patients were included in the study, 243 (53%) had 1+ EMS-ED events, 90 (20%) never required an EMS-ED at last follow-up, and 69 (15%) and 53 (12%) experienced transplant or death as their first event, respectively. The mean age of the cohort was 62 ± 15 years, 89% were Caucasian, and 35% were female sex. Patients were highly comorbid and 97/381 (25.5%) with available data on frailty severity had a CFS score of ≥5, inclusive of CFS scores ranging from mildly to severely frail. After adjustment, a CFS score of ≥5 (relative to 1-2) was associated with a > 2-fold increase in the risk of first EMS-ED (subdistribution relative hazard; SHR 2.28, 95% confidence interval; CI 1.30-3.98). A history of peripheral vascular disease (SHR 1.43, 95% CI 1.00-2.03) and rheumatologic disease (SHR 1.84, 95% CI 1.00-3.38) was also associated with first EMS-ED. Frailty severity was the only factor associated with recurrent EMS-ED. Conclusion: Patients are at a high risk of EMS-ED after dialysis initiation. Frailty severity (at the time of dialysis initiation) is a strong predictor of first and recurrent EMS-ED and this may be important to guide informed decision making and resource planning for dialysis patients who require EMS.

Background: Routine testing of hemodialysis patients for COVID-19 (outside of those identified as "at risk" based on regional practice) is not universally recommended. However, there is variability in the clinical presentation of COVID-19; patients may experience symptoms that do not meet regional criteria for testing and some patients with active infection may be asymptomatic. To avoid missing individuals who are infected, consideration could be made for regular screening, particularly among those residing in areas with evidence of community spread., Objective: To describe the clinical characteristics, symptom burden, and COVID-19 status in a cross-section of hemodialysis patients residing in areas with evidence of community spread., Design: Cross-sectional study., Setting: Three hemodialysis units in a large tertiary care facility in Nova Scotia, Canada., Patients: In-center hemodialysis patients who resided in areas with evidence of community transmission at the time of the study., Methods: All dialysis patients (irrespective of whether or not they resided in areas with community spread) completed a standard "at-risk" questionnaire for COVID-19 based on (1) 2 or more of new or worsening cough, fever greater than 38°C, sore throat, headache, runny nose/new or acute respiratory illness consistent with infection or (2) any one of close contact with a known/suspected case, travel outside of the province or residence in a facility with an outbreak prior to entry into the dialysis unit at each treatment. Patients residing in areas with evidence of community spread were swabbed for SARS-CoV-2 over a 1-week period (May 1-7, 2020) using a combined oropharyngeal/nares swab irrespective of whether or not they were identified as "at-risk.", Measurements: Baseline characteristics of patients were acquired using electronic records. In addition to the "at-risk" questionnaire, patients answered "yes" or "no" to any of the following symptoms at the time of the swab (sneeze, fatigue, myalgia, nausea/vomiting, diarrhea, malaise, abdominal pain, loss of taste, and loss of smell)., Results: Of the 334 patients receiving dialysis at the time of the study, 133 resided in areas with evidence of community transmission and 104 consented for the study. No patients met our regional criteria for being "at-risk" and no patients reported cough, sore throat or fever at the time of swab. Many other symptoms were noted, including sneezing (24%), fatigue (16%), myalgias (11%), nausea/vomiting (11%), loss of taste (4%), and loss of smell (4%). Overall, 100% of swabs performed for this study were negative for SARS-CoV-2., Limitations: Single-center study, and the daily new case rate was exceedingly low (4-14) at the time of the study, emphasizing that the findings are not generalizable to areas of higher prevalence of SARS-CoV-2., Conclusions: In this study of hemodialysis patients residing in areas with community spread who otherwise did not meet symptom criteria for being "at-risk," we did not identify any individual who tested positive for SARS-CoV-2. Future studies are needed to examine the utility of routine testing for COVID-19 (outside of those who are "at-risk") in areas of higher disease prevalence., Trial Registration: Not applicable as this is not a clinical trial., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Purpose of Review: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients., Sources of Information: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD., Methods: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions., Key Findings: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool., Limitations: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.M.H. has received investigator-initiated research funding from OPKO Health, Inc (OPKO Renal Division) and Sanofi. R.A.M. has received research funding from the Patient-Centered Outcomes Research Institute (PCORI), the American Society of Hematology (ASH), and the American College of Rheumatology (ACR). R.T.A. has received consulting honoraria from Ardelyx, Inc and from Advicenne. M.B. has received honoraria for advisory board membership with Otsuka Canada Pharmaceutical Inc (OCPI) and AstraZeneca. M.U.B. has received honoraria for consultation, advisory board membership, speaking engagements, or research funding from Janssen, OCPI, and Sanofi. G.K. declared no conflicts of interest. F.M.-W. has received honoraria for conferences, advisory board membership, or research funding from Amgen Inc, Otsuka Canada Pharmaceutical Inc, and Sanofi. M.R. declared no conflicts of interest. R.W. declared no conflicts of interest. P.D.A. declared no conflicts of interest. P.F. has no conflicts of interest. A.G. declared no conflicts of interest. K.K.J. has received honoraria for consultation or advisory board membership from Boehringer Ingelheim, Baxter, Amgen Inc, Sanofi, Eli Lilly and Company, LEO Pharma Inc Canada, and AstraZeneca. M.K. declared no conflicts of interest. B.A.K. declared no conflicts of interest. S.M. has received honoraria for consultation, advisory board membership, research funding, unrestricted grants, and educational grants from the Ontario Ministry of Health, NGX, Health Canada, Nutrigenomix Inc, Mitacs, Central East Local Health Integration Network, Ontario Renal Network (ORN), Sanofi, Shire, Amgen Inc, Sanofi Genzyme, Boehringer Ingelheim, and Baxter. K.M. declared no conflicts of interest. A.M. declared no conflicts of interest. M.P. declared no conflicts of interest. C.R. declared no conflicts of interest. S.D.S. has received honoraria for consultation, advisory board membership, and Canadian Medical Education (CME) lectures from the, Sanofi, Pfizer Inc, Janssen Inc, Amgen Inc, and Otsuka Canada Pharmaceutical Inc. A.J.V. has received honoraria for consultation from Paladin Labs Inc. D.Z. has received investigator-initiated research funding from Sanofi and has been a member of advisory boards for Otsuka Canada Pharmaceutical Inc, and Amgen Inc. C.M.C. has received honoraria for consultation, advisory board membership, or research funding from the Ontario Ministry of Health, Sanofi, Pfizer Inc, LEO Pharma Inc Canada, Astellas, Janssen Inc, Amgen Inc, Boehringer Ingelheim, and Baxter., (© The Author(s) 2020.)

Background: The consequences of prolonging cold ischemia time (CIT) to facilitate HLA matching in kidney transplantation are not known., Methods: Patients with a history of kidney transplant in the United States (2000-2016) with 0 HLA mismatch (MM) were categorized based on CIT (< 10; 10 to < 15; 15 to < 20; 20 to < 25; 25 to < 30; and ≥ 30 hours). Time to graft loss was compared for each CIT category to a reference group of individuals with > 0 HLA MM and short CIT (< 10 hours) using a multivariable Cox proportional hazards model., Results: The adjusted risk of graft failure was significantly lower for 0 HLA MM with the shortest CIT compared to the reference group (hazard ratio, 0.82; 95% confidence interval, 0.72-0.94), and this survival advantage persisted to a threshold of < 20 hours of CIT. No survival advantage was observed for the 0 HLA MM group once CIT was > 20 hours. This trend persisted after excluding highly sensitized recipients (panel reactive antibody > 98%) where shipping of organs occurs to achieve more equitable access to organs rather than optimize HLA match., Conclusions: CIT > 20 hours offsets the benefit of 0 HLA MM in kidney transplantation. This may have implications in organ shipping to facilitate immunologic match., (Copyright © 2020 Elsevier Inc. All rights reserved.)