Surgical Treatment of Medically Refractory Encapsulating Peritoneal Sclerosis in a Patient After Kidney Transplant.

Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has been described in patients with encapsulation of bowel causing obstruction. Here, we describe a case of surgical management in a patient following kidney transplant with medically refractory ascites and lower extremity edema.

Targeted Quantification of Proteoforms in Complex Samples by Proteoform Reaction Monitoring.

Existing mass spectrometric assays used for sensitive and specific measurements of target proteins across multiple samples, such as selected/multiple reaction monitoring (SRM/MRM) or parallel reaction monitoring (PRM), are peptide-based methods for bottom-up proteomics. Here, we describe an approach based on the principle of PRM for the measurement of intact proteoforms by targeted top-down proteomics, termed proteoform reaction monitoring (PfRM). We explore the ability of our method to circumvent traditional limitations of top-down proteomics, such as sensitivity and reproducibility. We also introduce a new software program, Proteoform Finder (part of ProSight Native), specifically designed for the easy analysis of PfRM data. PfRM was initially benchmarked by quantifying three standard proteins. The linearity of the assay was shown over almost 3 orders of magnitude in the femtomole range, with limits of detection and quantification in the low femtomolar range. We later applied our multiplexed PfRM assay to complex samples to quantify biomarker candidates in peripheral blood mononuclear cells (PBMCs) from liver-transplanted patients, suggesting their possible translational applications. These results demonstrate that PfRM has the potential to contribute to the accurate quantification of protein biomarkers for diagnostic purposes and to improve our understanding of disease etiology at the proteoform level.

Prognostic Biomarkers in Kidney Transplantation: A Systematic Review and Critical Appraisal.

SIGNIFICANCE STATEMENT: Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events. Less than 5% of the studies performed an external validation. The authors also showed the poor transparency reporting and identified a data beautification phenomenon. These findings suggest that there is much wasted research effort in transplant biomarker medical research and highlight the need to produce more rigorous studies so that more biomarkers may be validated and successfully implemented in clinical practice. BACKGROUND: Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology, and reporting might contribute to this phenomenon. METHODS: We formed a consortium of experts in systematic reviews, nephrologists, methodologists, and epidemiologists. A systematic literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library between January 1, 2005, and November 12, 2022 (PROSPERO ID: CRD42020154747). All English language, original studies investigating the association between a biomarker and kidney allograft outcome were included. The final set of publications was assessed by expert reviewers. After data collection, two independent reviewers randomly evaluated the inconsistencies for 30% of the references for each reviewer. If more than 5% of inconsistencies were observed for one given reviewer, a re-evaluation was conducted for all the references of the reviewer. The biomarkers were categorized according to their type and the biological milieu from which they were measured. The study characteristics related to the design, methods, results, and their interpretation were assessed, as well as reproducible research practices and transparency indicators. RESULTS: A total of 7372 publications were screened and 804 studies met the inclusion criteria. A total of 1143 biomarkers were assessed among the included studies from blood ( n =821, 71.8%), intragraft ( n =169, 14.8%), or urine ( n =81, 7.1%) compartments. The number of studies significantly increased, with a median, yearly number of 31.5 studies (interquartile range [IQR], 23.8-35.5) between 2005 and 2012 and 57.5 (IQR, 53.3-59.8) between 2013 and 2022 ( P < 0.001). A total of 655 studies (81.5%) were retrospective, while 595 (74.0%) used data from a single center. The median number of patients included was 232 (IQR, 96-629) with a median follow-up post-transplant of 4.8 years (IQR, 3.0-6.2). Only 4.7% of studies were externally validated. A total of 346 studies (43.0%) did not adjust their biomarker for key prognostic factors, while only 3.1% of studies adjusted the biomarker for standard-of-care patient monitoring factors. Data sharing, code sharing, and registration occurred in 8.8%, 1.1%, and 4.6% of studies, respectively. A total of 158 studies (20.0%) emphasized the clinical relevance of the biomarker, despite the reported nonsignificant association of the biomarker with the outcome measure. A total of 288 studies assessed rejection as an outcome. We showed that these rejection studies shared the same characteristics as other studies. CONCLUSIONS: Biomarker studies in kidney transplantation lack validation, rigorous design and methodology, accurate interpretation, and transparency. Higher standards are needed in biomarker research to prove the clinical utility and support clinical use.

Evaluation of Opening Offers Early for Deceased Donor Kidneys at Risk of Nonutilization.

BACKGROUND: Reducing nonutilization of kidneys recovered from deceased donors is a current policy concern for kidney allocation in the United States. The likelihood of nonutilization is greater with a higher kidney donor risk index (KDRI) offer. We examine how opening offers for organs with KDRI >1.75 to the broader waitlist at varying points of time affects usage rates. METHODS: We simulate kidney allocation using data for January 2018 to June 2019 from Organ Procurement and Transplantation Network. For the simulation experiment, allocation policy is modified so that KDRI >1.75 organs are offered to all local candidates (same donation service area) after a set amount of cold time simultaneously. Open offers to candidates nationally are similarly examined. RESULTS: Simulation results ( n =50 replications) estimate that opening offers locally for KDRI >1.75 after 10 hours yields a nonutilization rate of 38% (range: 35%-42%), less than the prevailing rate of 55% of KDRI >1.75 kidneys. Opening offers after 5 hours yields 30% (range: 26%-34%), reducing the prevailing nonutilization rate by 45%. Opening offers nationally after 10 and 5 hours yields nonutilization rates of 11% (range: 8%-15%) and 6% (range: 4%-9%) for KDRI >1.75 kidneys, respectively. CONCLUSIONS: Simulation findings indicate that opening offers and adjusting their timing can significantly reduce nonutilization of high-KDRI kidneys.

Kidney organ allocation: reducing discards.

PURPOSE OF REVIEW: The donation and kidney transplant system in the United States is challenged with reducing the number of kidneys that are procured for transplant but ultimately discarded. That number can reach 20% of donated kidneys each year. RECENT FINDINGS: The reasons for these discards, in the face of overwhelming demand, are multiple. SUMMARY: The authors review the data supporting a number of potential causes for high discard rates as well as provide potential solutions to the problem.

European Society of Organ Transplantation Consensus Statement on Testing for Non-Invasive Diagnosis of Kidney Allograft Rejection.

To address the need for improved biomarkers for kidney transplant rejection, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in kidney transplant biomarkers to review literature pertaining to clinical and subclinical acute rejection to develop guidelines in the screening and diagnosis of acute rejection that were subsequently discussed and voted on during the Consensus Conference that took place in person in Prague. The findings and recommendations of the Working Group on Molecular Biomarkers of Kidney Transplant Rejection are presented in this article.

Patient Preferences for Waiting Time and Kidney Quality.

BACKGROUND AND OBJECTIVES: Approximately 20% of deceased donor kidneys are discarded each year in the United States. Some of these kidneys could benefit patients who are waitlisted. Understanding patient preferences regarding accepting marginal-quality kidneys could help more of the currently discarded kidneys be transplanted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study uses a discrete choice experiment that presents a deceased donor kidney to patients who are waiting for, or have received, a kidney transplant. The choices involve trade-offs between accepting a kidney today or a future kidney. The options were designed experimentally to quantify the relative importance of kidney quality (expected graft survival and level of kidney function) and waiting time. Choices were analyzed using a random-parameters logit model and latent-class analysis. RESULTS: In total, 605 participants completed the discrete choice experiment. Respondents made trade-offs between kidney quality and waiting time. The average respondent would accept a kidney today, with 6.5 years of expected graft survival (95% confidence interval, 5.9 to 7.0), to avoid waiting 2 additional years for a kidney, with 11 years of expected graft survival. Three patient-preference classes were identified. Class 1 was averse to additional waiting time, but still responsive to improvements in kidney quality. Class 2 was less willing to accept increases in waiting time for improvements in kidney quality. Class 3 was willing to accept increases in waiting time even for small improvements in kidney quality. Relative to class 1, respondents in class 3 were likely to be age ≤61 years and to be waitlisted before starting dialysis, and respondents in class 2 were more likely to be older, Black, not have a college degree, and have lower Karnofsky performance status. CONCLUSIONS: Participants preferred accepting a lower-quality kidney in return for shorter waiting time, particularly those who were older and had lower functional status.

Implications of Accumulated Cold Time for US Kidney Transplantation Offer Acceptance.

BACKGROUND AND OBJECTIVES: Reducing discard is important for the US transplantation system because nearly 20% of the deceased donor kidneys are discarded. One cause for the discards is the avoidance of protracted cold ischemia times. Extended cold ischemia times at transplant are associated with additional risk of graft failure and patient mortality. A preference for local (within the same donor service area) or low-Kidney Donor Risk Index organs, the endogeneity of cold ischemia time during organ allocation, and the use of provisional offers all complicate the analysis of cold ischemia times' influence on kidney acceptance decision making. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using January 2018 to June 2019 Organ Procurement and Transplantation Network data, we modeled the probability of accepting an offer for a kidney after provisional acceptance. We use logistic regression that includes cold ischemia time, Kidney Donor Risk Index, and other covariates selected from literature. Endogeneity of cold ischemia time was treated by a two-stage instrumental variables approach. RESULTS: Logistic regression results for 3.33 million provisional acceptances from 12,369 donors and 108,313 candidates quantify trade-offs between cold ischemia time at the time of offer acceptance and donor-recipient characteristics. Overall, each additional 2 hours of cold ischemia time affected acceptance for nonlocal and local recipients (odds ratio, 0.75; 95% confidence interval, 0.73 to 0.77, odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91; P<0.001). For Kidney Donor Risk Index >1.75 (Kidney Donor Profile Index >85) kidneys, an additional 2 hours of cold ischemia time for nonlocal and local recipients was associated with acceptance with odds ratio, 0.58; 95% confidence interval, 0.54 to 0.63 (nonlocal) and odds ratio, 0.65; 95% confidence interval, 0.6 to 0.7 (local); P<0.001. The effect of an additional 2 hours of cold ischemia time on acceptance of kidneys with Kidney Donor Risk Index ≤1.75 (Kidney Donor Profile Index ≤85) was less pronounced for nonlocal offers (odds ratio, 0.82; 95% confidence interval, 0.80 to 0.85; P<0.001) and not significant for local offers. CONCLUSIONS: The acceptability of marginal organs was higher when placements were nearer to the donor and when cold ischemia time was shorter.

One-Year Outcomes of the Multi-Center StudY to Transplant Hepatitis C-InfeCted kidneys (MYTHIC) Trial.

INTRODUCTION: Transplanting kidneys from hepatitis C virus (HCV) viremic donors into HCV-negative patients (HCV D-RNA-positive/R-negative) has evolved from experimental to "standard-of-care" at many centers. Nevertheless, most data derive from single centers and provide only short-term follow-up. METHODS: The Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC) study was a multicenter (7 sites) trial of HCV D-RNA-positive/R-negative kidney transplantation (KT) followed by 8 weeks of glecaprevir/pibrentasvir (G/P) initiated 2 to 5 days post-KT. Prespecified outcomes included probability of KT (vs. matched waitlist comparators) and 1-year safety outcomes, allograft function, and survival. RESULTS: Among 63 enrolled patients, 1-year cumulative incidence of KT was approximately 3.5-fold greater for the MYTHIC cohort versus 2055 matched United Network for Organ Sharing (UNOS) comparators who did not opt-in to receive a kidney from an HCV-viremic donor (68% vs. 19%, P < 0.0001). Of 30 HCV D-RNA-positive/R-negative KT recipients, all achieved HCV cure. None developed clinically significant liver disease or HCV-related kidney injury. Furthermore, 1-year survival was 93% and 1-year graft function was excellent (median creatinine 1.17; interquartile range [IQR]: 1.02-1.38 mg/dl). There were 4 cases of cytomegalovirus (CMV) disease among 10 CMV-negative patients transplanted with a kidney from an HCV-viremic/CMV-positive donor. CONCLUSION: The 1-year findings from this multicenter trial suggest that opting-in for HCV-viremic KT offers can increase probability of KT with excellent 1-year outcomes. Trial Registration: NCT03781726.

Dynamic prediction of renal survival among deeply phenotyped kidney transplant recipients using artificial intelligence: an observational, international, multicohort study.

BACKGROUND: Kidney allograft failure is a common cause of end-stage renal disease. We aimed to develop a dynamic artificial intelligence approach to enhance risk stratification for kidney transplant recipients by generating continuously refined predictions of survival using updates of clinical data. METHODS: In this observational study, we used data from adult recipients of kidney transplants from 18 academic transplant centres in Europe, the USA, and South America, and a cohort of patients from six randomised controlled trials. The development cohort comprised patients from four centres in France, with all other patients included in external validation cohorts. To build deeply phenotyped cohorts of transplant recipients, the following data were collected in the development cohort: clinical, histological, immunological variables, and repeated measurements of estimated glomerular filtration rate (eGFR) and proteinuria (measured using the proteinuria to creatininuria ratio). To develop a dynamic prediction system based on these clinical assessments and repeated measurements, we used a Bayesian joint models-an artificial intelligence approach. The prediction performances of the model were assessed via discrimination, through calculation of the area under the receiver operator curve (AUC), and calibration. This study is registered with ClinicalTrials.gov, NCT04258891. FINDINGS: 13 608 patients were included (3774 in the development cohort and 9834 in the external validation cohorts) and contributed 89 328 patient-years of data, and 416 510 eGFR and proteinuria measurements. Bayesian joint models showed that recipient immunological profile, allograft interstitial fibrosis and tubular atrophy, allograft inflammation, and repeated measurements of eGFR and proteinuria were independent risk factors for allograft survival. The final model showed accurate calibration and very high discrimination in the development cohort (overall dynamic AUC 0·857 [95% CI 0·847-0·866]) with a persistent improvement in AUCs for each new repeated measurement (from 0·780 [0·768-0·794] to 0·926 [0·917-0·932]; p<0·0001). The predictive performance was confirmed in the external validation cohorts from Europe (overall AUC 0·845 [0·837-0·854]), the USA (overall AUC 0·820 [0·808-0·831]), South America (overall AUC 0·868 [0·856-0·880]), and the cohort of patients from randomised controlled trials (overall AUC 0·857 [0·840-0·875]). INTERPRETATION: Because of its dynamic design, this model can be continuously updated and holds value as a bedside tool that could refine the prognostic judgements of clinicians in everyday practice, hence enhancing precision medicine in the transplant setting. FUNDING: MSD Avenir, French National Institute for Health and Medical Research, and Bettencourt Schueller Foundation.

Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. RESULTS: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P<0.001) or donor-derived cfDNA alone (P=0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P=0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P=0.003). CONCLUSIONS: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection.

Are borderline changes real rejection? Current viewpoints.

PURPOSE OF REVIEW: The clinical significance and treatment of borderline changes are controversial. The lowest detectable margin for rejection on histology is unclear. We review recent evidence about borderline changes and related biomarkers. RECENT FINDINGS: Borderline change (Banff ≥ t1i1) is associated with progressive fibrosis, a greater propensity to form de-novo DSA, and reduced graft survival. Isolated tubulitis appears to have similar kidney allograft outcomes with normal controls, but this finding should be validated in a larger, diverse population. When borderline change was treated, a higher chance of kidney function recovery and better clinical outcomes were observed. However, spontaneous borderline changes resolution without treatment was also observed. Various noninvasive diagnostic biomarkers have been developed to diagnose subclinical acute rejection, including borderline changes and ≥ Banff 1A TCMR. Biomarkers using gene expression and donor-derived cell-free DNA, and HLA DR/DQ eplet mismatch show potential to diagnose subclinical acute rejection (borderline change and ≥Banff 1A TCMR), to avoid surveillance biopsy, or to predict poor kidney allograft outcomes. SUMMARY: Borderline changes are associated with poor kidney allograft outcomes, but it remains unclear if all cases of borderline changes should be treated. Novel biomarkers may inform physicians to aid in the diagnosis and treatment.

Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection.

BACKGROUND: Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. METHODS: We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. RESULTS: We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. CONCLUSIONS: Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.

Physician and patient acceptance of policies to reduce kidney discard.

Despite the shortage of kidneys for transplantation in the United States, approximately 18%-20% of deceased donor kidneys are discarded each year. These discarded kidneys can offer a survival benefit to suitable patients. Revisions to the current kidney allocation policy may be needed to reduce deceased donor kidney discard. We surveyed transplant physicians and patients to assess their perceived acceptability of policy proposals to reduce the discard of deceased donor kidneys. Members of professional societies (AST, ASTS) and a patient organization (AAKP) were invited to complete the survey. Responses were obtained from 97 physicians and 107 patients. The majority of physicians (73.4%) and patients (73.8%) "somewhat" or "completely" accepted a policy for fast-tracking kidneys at risk of discard. Physicians and patients also supported returning a proportion of waiting time to patients who accept KDPI >85 kidneys and experience graft failure within the first 12 months, with 36% of physicians and 50% of patients electing to return 100% of the waiting time. The majority of physicians (75%) "somewhat or completely" accepted a policy to skip less aggressive centers for KDPI 90 + offers. Physicians and patients provided insights into factors researchers, and policymakers should consider in the design and implementation of these policies.

Correction to: Trends and predictors of multidimensional health-related quality of life after living donor kidney transplantation.

In its original publication, an erroneous version of Fig. 2d was included in the manuscript. The corrected figure has now been added.

Kidney Graft Surveillance Biopsy Utilization and Trends: Results From a Survey of High-Volume Transplant Centers.

An e-mail-based market research survey focused on high-volume US adult transplant centers was developed and implemented to assess surveillance based on United Network for Organ Sharing/Scientific Registry of Transplant Recipients data: 51 to 100 transplants, 101 to 200 transplants, and more than 200 transplants. Eighty-three centers responded to the survey. Respondent centers represented 13,837/21,167 (65%) of the total kidney transplants in 2018. In total, 38/83 (46%) centers reported the use of surveillance biopsies-20 centers in all patients and 18 in select patients. Surveillance biopsies were performed in 37% (7/19) of centers performing 51 to 100 transplants annually, in 44% (15/34) doing 101 to 200 transplants, and in 53% (16/30) of centers doing more than 200 transplants. Of the 20 centers doing surveillance biopsies in all patients, 17/20 (85%) perform more than 100 annual transplants, and 3/20 (15%) perform less than 100 annual transplants. Of the 45 centers not currently doing surveillance biopsies, 13 (29%) used surveillance biopsies in the past; discontinuation was primarily due to patient inconvenience, adverse events, and cost. Using survey percentages, it is estimated that surveillance biopsies are performed in approximately 34% of kidney transplant recipients and that 74% of all surveillance biopsies occur in centers performing more than 100 kidney transplants per year.

Trends and predictors of multidimensional health-related quality of life after living donor kidney transplantation.

PURPOSE: Living donor kidney transplant (LDKT) imparts the best graft and patient survival for most end-stage kidney disease (ESKD) patients. Yet, there remains variation in post-LDKT health-related quality of life (HRQOL). Improved understanding of post-LDKT HRQOL can help identify patients for interventions to maximize the benefit of LDKT. METHODS: For 477 LDKT recipients transplanted between 11/2007 and 08/2016, we assessed physical, mental, social, and kidney-targeted HRQOL pre-LDKT, as well as 3 and 12 months post-operatively using the SF-36, Kidney Disease Quality of Life-Short Form (KDQOL-SF), and the Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 item version (FKSI-19). We then examined trajectories of each HRQOL domain using latent growth curve models (LGCMs). We also examined associations between decline in HRQOL from 3 months to 12 months post-LDKT and death censored graft failure (DCGF) using Cox regression. RESULTS: Large magnitude effects (d > 0.80) were observed from pre- to post-LDKT change on the SF-36 Vitality scale (d = 0.81) and the KDQOL-SF Burden of Kidney Disease (d = 1.05). Older age and smaller pre- to post-LDKT decreases in serum creatinine were associated with smaller improvements on many HRQOL scales across all domains in LGCMs. Higher DCGF rates were associated with worse physical [e.g., SF-36 PCSoblique hazard ratio (HR) 1.18; 95% CI 1.01-1.38], mental (KDQOL-SF Cognitive Function HR 1.27; 95% CI 1.00-1.62), and kidney-targeted (FKSI-19 HR: 1.18; 95% CI 1.00-1.38) HRQOL domains. CONCLUSION: Clinical HRQOL monitoring may help identify patients who are most likely to have failing grafts and who would benefit from post-LDKT intervention.