Donor Candidates Research Articles

OPTN/SRTR 2020 Annual Data Report: Living Donor Collective

The first successful solid organ transplant was a living donor kidney transplant in 1954. Since then, living donation has been an important source of organs for kidney and liver transplants in the United States. Unfortunately, the demand for organs has not kept pace with the supply, and unlike deceased donor transplant, there has been little growth in the number of living donor transplants over the past decade. To better understand possible barriers to living donation and long-term risks attributable to donation, the Health Resources and Services Administration (HRSA) directed the Scientific Registry of Transplant Recipients (SRTR) to establish a national registry of all living donor candidates and donors evaluated at US transplant programs to acquire lifetime follow-up information. Other goals include understanding the factors associated with candidate approval and variation in approval practices across centers. A pilot program was conducted from June 2018 through September 2020 to inform baseline data collection and registration processes. In September 2020, the registry began recruiting additional sites evaluating candidates for living donation. Here, we describe candidates registered at participating living donor kidney and liver programs, from June 2018 through the end of 2020. Not all programs submitted data throughout the whole period. Data for kidney and liver living donor candidates are presented separately.

Coronavirus Precautions: Experience of High Volume Liver Transplant Institute.

To present the struggle of a high volume liver transplant center against coronavirus infectious disease-2019 pandemic. Between March 2020 and December 2020, the demographic and clinical data of staff and liver transplant candidates diagnosed with coronavirus infectious disease-2019 in our Liver Transplant Institute were prospectively analyzed. First, 32 healthcare staff were diagnosed with coronavirus infectious disease-2019, and 6 of them were surgeons. Six staff were asymptomatic, while 24 staff had mild or moderate and 2 staff had severe coronavirus infectious disease-2019. All the staff recovered from the disease without any permanent sequela and returned to duty after 2 consecutive negative polymerase chain reaction results within 24-hour intervals. Second, during the preoperative investigation, 6 living liver donor candidates and 13 recipients were tested positive for coronavirus infectious disease-2019 (son = 6, unrelated = 3, cousin = 3, daughter = 2, cadaveric = 1). Eleven patients received favipiravir and 8 did not receive any treatment because they were asymptomatic. Only one recipient who had severe coronavirus infectious disease-2019 died due to multiple organ failure syndrome. One recipient died in the early postoperative period. The median duration from the initial diagnosis of the patients till the transplant procedure was 21 days (min-max: 14-105 days). During the time of operation, the polymerase chain reaction tests of the donors and the recipients were negative, and the thorax tomography images showed no signs of viral pneumonia. Meticulous precautions, multidisciplinary approach, team effort, and organization of facilities can increase the quality of care of these patients in the coronavirus infectious disease-2019 era. Healthcare workers have shown tremendous effort and are the true heroes of this era.

Microbiological Quality of Milk Donated to the Regional Human Milk Bank in Warsaw in the First Four Years of Activity.

As the survival rate for preterm infants increases, more emphasis is placed on improving health-related quality of life through optimal nutritional management. Human Milk Banks (HMBs) provide bioactive nutrients and probiotic microorganisms to premature newborns, especially in the first year of life. Donated milk screening and selection of potential donors ensures the quality and microbiological safety of the donated milk. Therefore we reviewed the basic characteristics of donors and the amounts and contamination of breast milk donated to the Regional Human Milk Bank (RHMB) in Warsaw. In four years, the RHMB collected 1445.59 L of milk, of which 96.60% was distributed among hospitalised infants. Additionally, breastmilk from donor candidates (139 samples from 96 women) was tested at least once in the first year of lactation. First analyses showed that 18 women’s milk samples were microbiologically pure, and 78 samples had one or more species of commensal and/or potentially pathogenic bacteria. In human milk samples from 10 women, the bacteria level was above the standard required by the RHMB; therefore, donors were re-educated, and further samples were tested. Most women followed the recommendations on hygienic expression and storage of milk before transfer to the RHMB. Our analysis will help to increase the accessibility and quality of raw donor milk and to meet the needs of more newborns.

Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.

Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.

Relevance of deceased donor proteinuria for kidney transplantation: A comprehensive national cohort study.

Proteinuria is frequent in patients with nephropathies and associated with progressive kidney disease and risk for end stage kidney disease. However, the relevance of deceased donor proteinuria on transplant outcome remains uncertain. In this nationwide cohort study, we evaluated the prevalence of proteinuria in deceased donor candidates and measured the impact on outcome after kidney transplantation. Data from the Swiss Organ Allocation System and the Swiss Transplant Cohort Study were analyzed, comprising 1725 donors and 1516 recipients transplanted between 2008 and 2019. We correlated urine findings with donor characteristics and quantified the impact of proteinuria on allograft function at 12months and survival. Proteinuria influenced allocation decisions in 4.5% of nonimmunological organ declines and was the leading cause for decline in 0.2% of cases. 74.1%, 51.4%, and 35.3% of donor candidates had a baseline proteinuria above 15, 30, and 50mg protein/mmol urine creatinine, respectively. Proteinuria above 30mg/mmol was associated with female donor sex, mechanical resuscitation, acute kidney injury, and time delay between ICU entry and urine sampling. Donor proteinuria was not associated with patient or allograft survival, nor allograft function at 12months. We report a high prevalence of proteinuria in donor candidates, without evidence of a deleterious impact of proteinuria on graft function and/or survival. Therefore, low-level proteinuria should not be considered a limiting contraindication for kidney allocation in deceased donor transplant.

Non-Contrast-Enhanced and Contrast-Enhanced Magnetic Resonance Angiography in Living Donor Liver Vascular Anatomy.

Background: Since the advent of a new generation of inflow-sensitive inversion recovery (IFIR) technology, three-dimensional non-contrast-enhanced magnetic resonance angiography is being used to obtain hepatic vessel images without applying gadolinium contrast agent. The purpose of this study was to explore the diagnostic efficacy of non-contrast-enhanced magnetic resonance angiography (non-CE MRA), contrast-enhanced magnetic resonance angiography (CMRA), and computed tomography angiography (CTA) in the preoperative evaluation of living liver donors. Methods: A total of 43 liver donor candidates who were evaluated for living donor liver transplantation completed examinations. Donors’ age, gender, renal function (eGFR), and previous CTA and imaging were recorded before non-CE MRA and CMRA. CTA images were used as the standard. Results: Five different classifications of hepatic artery patterns (types I, III, V, VI, VIII) and three different classifications of portal vein patterns (types I, II, and III) were identified among 43 candidates. The pretransplant vascular anatomy was well identified using combined non-CE MRA and CMRA of hepatic arteries (100%), PVs (98%), and hepatic veins (100%) compared with CTA images. Non-CE MRA images had significantly stronger contrast signal intensity of portal veins (p < 0.01) and hepatic veins (p < 0.01) than CMRA. No differences were found in signal intensity of the hepatic artery between non-CE MRA and CMRA. Conclusion: Combined non-CE MRA and CMRA demonstrate comparable diagnostic ability to CTA and provide enhanced biliary anatomy information that assures optimum donor safety.

Approach to genetic testing to optimize the safety of living donor transplantation in Alport syndrome spectrum.

Alport syndrome spectrum can be considered as a group of genetic diseases affecting the major basement membrane collagen type IV network in various organs including the ear, eye, and kidney. The living donor candidate evaluation is an ever-changing landscape. Recently, next-generation sequence (NGS) panels have become readily available and provide opportunities to genetically screen recipient and donor candidates for collagen network gene variants. In this review, our aim is to provide a comprehensive update on the role of genetic testing for the evaluation of potential living kidney donors to kidney candidates with Alport syndrome spectrum. We examine the utility of genetic testing in the evaluation of potential donors for recipients with Alport syndrome spectrum, and discuss risks and unresolved challenges. Suggested algorithms in the context of related and unrelated donation are offered. In contemporary practice, an approach to the evaluation of living donor candidates for transplant candidates with Alport syndrome spectrum can incorporate genetic testing in algorithms tailored for donor-recipient relationship status. Ongoing research is needed to inform optimal practice.

Estimating Extracellular Fluid Volume in Healthy Individuals: Evaluation of Existing Formulae and Development of a New Equation

IntroductionSeveral clinical settings require an accurate estimation of the physiologically expected extracellular fluid volume (ECFV). We aimed to analyze the performances of existing ECFV-estimating equations and to develop a new equation.MethodsThe performances of 11 ECFV-estimating equations were analyzed in 228 healthy kidney donor candidates (Bichat Hospital, Paris, France) who underwent ECFV measurement using the distribution volume of 51Cr-labeled EDTA (51Cr-EDTA). An equation was developed using a penalized linear modeling approach (elastic net regression) and externally (Tenon Hospital, Paris, France, N = 142) validated.ResultsParticipants from Bichat (mean age 45.2 ± 12.0 years, 43.0% men) and Tenon (47.8 ± 10.3 years, 29.6% men) hospitals had a mean measured ECFV of 15.4 ± 2.8 l and 15.1 ± 2.1 l, respectively. Available ECFV-estimating formulae have highly variable precision and accuracy. The new equation incorporating body weight, height, sex, and age had better precision and accuracy than all other equations in the external validation cohort, with a median bias of −0.20 (95% CI: −0.35 to −0.05) l versus −2.63 (−2.87 to −2.42) l to −0.57 (− 0.83 to −0.40) l and 0.21 (0.12 to 0.43) l to 2.89 (2.65 to 3.11) l, for underestimating and overestimating equations, respectively, an interquartile range for the bias of 0.88 (0.70 to 1.08) l versus 0.91 (0.71 to 1.20) l to 1.93 (1.67 to 2.25) l, and an accuracy within 10% of 90.9% (83.8 to 94.4) versus 88.0% (81.0 to 92.3) to 8.5% (4.2 to 13.4). These results were consistent across subgroups defined by sex, body mass index (BMI), body surface area (BSA), age, and ethnicity.ConclusionWe developed and validated a new equation to estimate the individual reference value of ECFV, which is easily usable in clinical practice. Further validation in cohorts including individuals of extreme age and corpulence remains needed.

Influence of Fluorine Substitution on the Photovoltaic Performance of Wide Band Gap Polymer Donors for Polymer Solar Cells.

The design and development of wide band gap (WBG) polymer donors are critical for achieving high power conversion efficiencies (PCEs) in polymer solar cells. In this work, four WBG polymer donors, Q4, Q5, Q6, and Q7, with different numbers and positions of fluorine substitution (n = 0, 2, 2, and 4, respectively) were prepared, and the effect of fluorination on their photovoltaic performance was systematically investigated. When blended with a small-molecule electron acceptor MeIC, the devices based on Q4, Q5, Q6, and Q7 showed PCEs of 10.34, 11.06, 5.26, and 0.48%, respectively. When coupled with a low band gap polymer acceptor PYIT to fabricate all-polymer solar cells (all-PSCs), while the other three polymers (Q5-Q7) exhibited much lower PCEs in the range of 0.12-6.71%, the Q4 polymer-based all-PSCs showed the highest PCE of 15.06%, comparable to that of the devices fabricated with the star polymer donor PM6 (PCE = 15.00%). Detailed physicochemical and morphological studies revealed that an over-substitution of F in Q7 results in undesired low-lying HOMO levels and phase separation with the acceptors, thus resulting in its inferior PCEs. Moreover, the less F-substitution and controlling of the positions of F-substitution position in Q4 and Q5 can improve the HOMO energy level matching as well as morphologies between these two polymers with the acceptors, which in turn gives rise to higher performances. Clearly, our results indicate that Q4 is a promising donor candidate for high-performance all-PSCs, and the fine-tuning of both the number and positions of F-substitution in the polymer backbone is essential in developing high-performance WBG polymer donors.

Comparison of low-dose contrast computed tomography angiography findings with surgical results in living kidney donors

Aim: To analyze the image quality and diagnostic performance of CT angiography using low dose (60 ml) contrast medium for living kidney donors and compare with surgical results.&#x0D; Material and Method: Angiographic findings of 81 renal donor candidates in 128-slice MDCT were evaluated by two independent radiologists in terms of renal artery number, early bifurcation, renal vein variations, pelvicalyceal system and ureter variations. Results were compared with intraoperative findings. The image quality, diagnostic performance and interobserver agreement of MDCT obtained with low dose contrast material were analyzed.&#x0D; Results: The mean age of the 81 living kidney donors included in the study was 49±12 (24-68) years. Left nephrectomy was performed in 71% (n=64) and right nephrectomy in 29% (n=17) of the donors. Intraoperative accessory arteries were detected in 22.2% (n:18) of the donors. The specificity, sensitivity, and accuracy for detecting accessory artery variation in MDCT were 100%, 88.9%, and 97.5%, respectively. Early bifurcation was observed in 21% (n=17) of the donors. Specificity, sensitivity and accuracy for early bifurcation detection were 98.4%, 94.1% and 97.5%, respectively. Renal vein variation was detected in 12.3% (n=10) of the donors. Specificity, sensitivity, and accuracy for renal vein variation detection were 100%. Variations of the pelvicalyceal system and ureter were observed in 3.7% (n=3) of the donors. The specificity, sensitivity, and accuracy for detecting pelvicalyceal system and ureteral variations were 100%. Interobserver agreement was excellent in detecting variations of accessory arteries, renal venous anomalies, pelvicalyceal system and ureters by MDCT (kappa: 1,000; p&lt; 0.001). It was higher in early bifurcation detection (kappa: 0.853; p&lt; 0.001).&#x0D; Conclusion: MDCT angiography with a lower dose of iodine contrast at 60 mL in kidney donors is sufficient to detect vascular anomalies and provide anatomical information. It is possible to reduce the contrast agent dose in CTA without affecting the preoperative evaluation.

Genetic associations with immune-mediated outcomes after allogeneic hematopoietic cell transplantation

AbstractPrevious studies have identified more than 200 genetic variants associated with acute or chronic graft-versus-host disease (aGVHD; cGVHD) or recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). We tested these candidate donor and recipient variants in a cohort of 4270 HCT recipients of European ancestry and in subcohorts of 1827 sibling and 1447 unrelated recipients who had 10/10 HLA-A, B, C, DRB1, and DQB1-matched donors. We also carried out a genome-wide association study (GWAS) for these same outcomes. The discovery and replication analysis of candidate variants identified a group of closely linked recipient HLA-DPB1 single-nucleotide polymorphisms (SNPs) associated with an increased risk of aGVHD and a corresponding decreased risk of recurrent malignancy after unrelated HCT. These results reflect a correlation with the level of HLA-DPB1 expression previously shown to affect the risks of aGVHD and relapse in unrelated recipients. Our GWAS identified an association of cGVHD with a locus of X-linked recipient intron variants in NHS, a gene that regulates actin remodeling and cell morphology. Evaluation of this association in a second replication cohort did not confirm the original replication results, and we did not reach any definitive conclusion regarding the validity of this discovery. The cohort used for our study is larger than those used in most previous HCT studies but is smaller than those typically used for other genotype-phenotype association studies. Genomic and disease data from our study are available for further analysis in combination with data from other cohorts.

Usability assessment of an interactive health technology for kidney living donors: protocol for a prospective cross-sectional survey

IntroductionSeveral web portals for kidney patients are available, but assessments of their performance are scarce. A crucial aspect of living donation is to provide standardised information about the risks of...

The Living Kidney Donor Safety Study: Protocol of a Prospective Cohort Study.

Living kidney donation is considered generally safe in healthy individuals; however, there is a need to better understand the long-term effects of donation on blood pressure and kidney function. To determine the risk of hypertension in healthy, normotensive adults who donate a kidney compared with healthy, normotensive non-donors with similar indicators of baseline health. We will also compare the 2 groups on the rate of decline in kidney function, the risk of albuminuria, and changes in health-related quality of life. Prospective cohort study of 1042 living kidney donors recruited before surgery from 17 transplant centers (12 in Canada and 5 in Australia) between 2004 and 2014. Non-donor participants (n = 396) included relatives or friends of the donor, or donor candidates who were ineligible to donate due to blood group or cross-match incompatibility. Follow-up will continue until 2021, and the main analysis will be performed in 2022. The anticipated median (25th, 75th percentile, maximum) follow-up time after donation is 7 years (6, 8, 15). Donors and non-donors completed the same schedule of measurements at baseline and follow-up (non-donors were assigned a simulated nephrectomy date). Annual measurements were obtained for blood pressure, estimated glomerular filtration rate (eGFR), albuminuria, patient-reported health-related quality of life, and general health. Incident hypertension (a systolic/diastolic blood pressure ≥ 140/90 mm Hg or receipt of anti-hypertensive medication) will be adjudicated by a physician blinded to the participant's donation status. We will assess the rate of change in eGFR starting from 12 months after the nephrectomy date and the proportion who develop an albumin-to-creatinine ratio ≥3 mg/mmol (≥30 mg/g) in follow-up. Health-related quality of life will be assessed using the 36-item RAND health survey and the Beck Anxiety and Depression inventories. Donation-attributable hypertension may not manifest until decades after donation. This prospective cohort study will estimate the attributable risk of hypertension and other health outcomes after living kidney donation.

Frequency of Living Donors with Comorbidity for Liver Transplantation: Analysis of 337 Cases

Introduction: Living donors for liver transplantation (LT) need to be physically and mentally healthy, but donor candidates sometimes have comorbidities and are forced to evaluate the suitability as donors. We examined the frequency of comorbidities in living liver donors. Patients and methods: Of 337 living donors for LT, except 67 cases with fatty liver, we investigated the preoperative comorbidities and perioperative management in living liver donors. Results: The number of donors with comorbidity was 95 (28%: 95/337), with a median age of 35 (23-57) years, 33 males, and 62 females. Relationships with recipients were 58 mothers, 28 fathers, 2 grandmothers, 2 sons, 5 others. The graft types were 62 lateral segments, 15 left lobes, 6 left lobes with caudate, 6 monosegments, 4 right lobes, and 2 posterior segments. A total of 107 comorbidities was recognized in 95 donors. Twenty-two cases with hepatic comorbidity were positive HBc antibodies, hepatic hemangiomas, drug-induced liver injuries, liver hamartoma, and congenital portosystemic shunt. Extrahepatic comorbidities were plasminogen disorder, obstructive respiratory disorder, lipid metabolism disorder, coagulation factor deficiency, iron deficiency anemia, hypertension, pollinosis, thyroid disease, menstrual abnormalities, postoperative gastrointestinal cancer, metabolic disease, benign ovarian tumor, arrhythmia, pregnancy, and others. We consulted with the department specializing in the comorbidity and closely performed preoperative evaluation and perioperative management according to each comorbidity. No case of complications due to each comorbidity was found. Conclusion: It is important to fully evaluate and determine the suitability of living donor candidates with comorbidities in collaboration with other departments.

Balancing Competing Interests in Disclosing Political Party and Candidate Donors

Balancing Competing Interests in Disclosing Political Party and Candidate Donors

Genetic counseling and carrier screening in candidates for gamete donation at a Portuguese center.

Genetic counseling and carrier screening are part of the gamete donation process by healthy individuals. We aim to review the findings of genetic counseling and carrier screening of a cohort of candidates at our public gametes bank. Thirty-four male and 64 female candidates had genetic counseling with a medical geneticist before donation. Of these, one female candidate voluntarily dropped-out. Thirty-four males and 63 females performed karyotype and screening for the more common pathogenic variants for CFTR-related cystic fibrosis and spinal muscular atrophy (SMN1) in the Portuguese population. In addition, all females also performed Fragile X expansion screening (FMR1). Thirty candidates with known or assumed African ancestry performed hemoglobinopathies screening. Six candidates were definitely or temporarily withheld from the donation process given their family or personal history that required further investigation. Of 97 candidates tested, 16.5% presented anomalous laboratory results (16/97): ten candidates were carriers for an autosomal recessive disorder - cystic fibrosis (5/97), sickle cell anemia (3/30), and spinal muscular atrophy (2/97). One female was an FMR1 pre-mutation carrier (1/63). One female candidate presented with triple X mosaicism: 47,XXX[2]/46,XX[50]. Two candidates presented with chromosomal instability of unknown origin. In one candidate, a mosaic for the Philadelphia chromosome was detected, revealing the diagnosis of chronic myeloid leukemia. From a cohort of 97 candidates, 21.7% had a family/personal history or an anomalous laboratory result that required additional genetic counseling, stressing the importance of performing pre-donation genetic counseling in this population.

MD Cycle Threshold and SARS-CoV-2 Infectivity

The ability of the cycle threshold to inform the infectivity of SARS-CoV-2 polymerase chain reaction (PCR)-positive individuals remains controversial. Berengua et al. have recently reported that in immunocompetent individuals SARS-CoV-2 infectivity lasts &lt; 15 days and that Ct value &gt; 27 indicates low probability for infectivity. This important study, however, comes with several caveats. The authors performed a single cell culture for each sample. Additionally, cycle threshold values and corresponding viral loads differ between variants. During the study period at least four strains were prevalent in Europe, yet the authors do not provide information regarding the isolated strains. Lastly, this hospital-based study seems to involve sampling bias. The findings of Berengua et al. may be leveraged to guide clinical decision in SARS-CoV-2 PCR-positive convalescing candidates for organ donation or transplantation.

Cutoff Values for Diagnosing Hepatic Steatosis Using Contemporary MRI-Proton Density Fat Fraction Measuring Methods.

To propose standardized MRI-proton density fat fraction (PDFF) cutoff values for diagnosing hepatic steatosis, evaluated using contemporary PDFF measuring methods in a large population of healthy adults, using histologic fat fraction (HFF) as the reference standard. A retrospective search of electronic medical records between 2015 and 2018 identified 1063 adult donor candidates for liver transplantation who had undergone liver MRI and liver biopsy within a 7-day interval. Patients with a history of liver disease or significant alcohol consumption were excluded. Chemical shift imaging-based MRI (CS-MRI) PDFF and high-speed T2-corrected multi-echo MR spectroscopy (HISTO-MRS) PDFF data were obtained. By temporal splitting, the total population was divided into development and validation sets. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the MRI-PDFF method. Two cutoff values with sensitivity > 90% and specificity > 90% were selected to rule-out and rule-in, respectively, hepatic steatosis with reference to HFF ≥ 5% in the development set. The diagnostic performance was assessed using the validation set. Of 921 final participants (624 male; mean age ± standard deviation, 31.5 ± 9.0 years), the development and validation sets comprised 497 and 424 patients, respectively. In the development set, the areas under the ROC curve for diagnosing hepatic steatosis were 0.920 for CS-MRI-PDFF and 0.915 for HISTO-MRS-PDFF. For ruling-out hepatic steatosis, the CS-MRI-PDFF cutoff was 2.3% (sensitivity, 92.4%; specificity, 63.0%) and the HISTO-MRI-PDFF cutoff was 2.6% (sensitivity, 88.8%; specificity, 70.1%). For ruling-in hepatic steatosis, the CS-MRI-PDFF cutoff was 3.5% (sensitivity, 73.5%; specificity, 88.6%) and the HISTO-MRI-PDFF cutoff was 4.0% (sensitivity, 74.7%; specificity, 90.6%). In a large population of healthy adults, our study suggests diagnostic thresholds for ruling-out and ruling-in hepatic steatosis defined as HFF ≥ 5% by contemporary PDFF measurement methods.

Assessment of Hepatic Steatosis Using Clinical and Laboratory Parameters with Computed Tomography Comparison in Living Liver Donor Candidates

Assessment of Hepatic Steatosis Using Clinical and Laboratory Parameters with Computed Tomography Comparison in Living Liver Donor Candidates

Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD): Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial.

Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) is a quality improvement intervention designed to enhance access to kidney transplantation and living kidney donation. We conducted a cluster-randomized clinical trial to evaluate the effect of the intervention versus usual care on completing key steps toward receiving a kidney transplant. To prespecify the statistical analysis plan for the EnAKT LKD trial. The EnAKT LKD trial is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized, superiority, clinical trial. Randomization was performed at the level of the chronic kidney disease (CKD) programs (the "clusters"). Twenty-six CKD programs in Ontario, Canada. More than 10 000 patients with advanced CKD (ie, patients approaching the need for dialysis or receiving maintenance dialysis) with no recorded contraindication to receiving a kidney transplant. The trial data (including patient characteristics and outcomes) will be obtained from linked administrative health care databases (the "registry"). Stratified covariate-constrained randomization was used to allocate the 26 CKD programs (1:1) to provide the intervention or usual care from November 1, 2017, to December 31, 2021 (4.17 years). CKD programs in the intervention arm received the following: (1) support for local quality improvement teams and administrative needs; (2) tailored education and resources for staff, patients, and living kidney donor candidates; (3) support from kidney transplant recipients and living kidney donors; and (4) program-level performance reports and oversight by program leaders. The primary outcome is completing key steps toward receiving a kidney transplant, where up to 4 unique steps per patient will be considered: (1) patient referred to a transplant center for evaluation, (2) a potential living kidney donor begins their evaluation at a transplant center to donate a kidney to the patient, (3) patient added to the deceased donor transplant waitlist, and (4) patient receives a kidney transplant from a living or deceased donor. Using an intent-to-treat approach, the primary outcome will be analyzed using a patient-level constrained multistate model adjusting for the clustering in CKD programs. The EnAKT LKD trial period is November 1, 2017, to December 31, 2021. We expect to analyze and report the results once the data for the trial period is available in linked administrative health care databases. The EnAKT LKD trial is registered with the U.S. National Institute of Health at clincaltrials.gov (NCT03329521 available at https://clinicaltrials.gov/ct2/show/NCT03329521). Version 1.0 August 26, 2022.