Challenges in the management of the kidney allograft: from decline to failure: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.

Kidney accelerated placement project: Outcomes and lessons learned.

Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplantation Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the Organ Center. The Kidney Accelerated Placement (KAP) project, implemented by the Organ Center from July 18, 2019 to July 15, 2020, aimed to offer kidneys with a high kidney donor profile index to programs that had a history of accepting such organs. We compared OPTN kidney match run, donor, and transplant recipient data during the project period and 1 year prior. There was no statistically significant change in the percentage of KAP-eligible donors accepted during the project period (16.4%) compared to the prior year (17.5%). Conversion from acceptance to transplant was higher under KAP (72.7% vs. 71.2%), though not significant. Waiting to accelerate placement after kidneys have been declined by multiple transplant programs locally and regionally is an intervention that may come too late to effectively increase utilization. Transplant rates of nationally shared and marginal kidneys remain a challenge, and future iterations of this project should be investigated.

Combined heart-liver-kidney transplant: The university of Chicago medicine experience.

BACKGROUND: Until recently, combined heart-liver-kidney transplantation was considered too complex or too high-risk an option for patients with end-stage heart failure who present with advanced liver and kidney failure as well. AIMS: The objective of this paper is to present our institution's best practices for successfully executing this highly challenging operation. At our institution, referral patterns are most often initiated through the cardiac team. RESULTS: Determinants of successful outcomes include diligent multidisciplinary patient selection, detailed perioperative planning, and choreographed care transition and coordination among all transplant teams. The surgery proceeds in three distinct phases with three different teams, linked seamlessly in planned handoffs. The selection and perioperative care are executed with determined collaboration of all of the invested care teams. CONCLUSIONS: Combined heart-liver-kidney transplantation can be successfully done by careful selection, coordination, and execution.

Utility of geriatric assessments in evaluation of older adults for kidney transplantation.

BACKGROUND: While kidney transplantation has favorable outcomes in patients aged 65 years and older, many are not referred for evaluation despite having no contraindications. We wanted to determine whether incorporating geriatrics and geriatric assessments (GA), as part of kidney transplant evaluation at the University of Chicago Medicine, would help identify suitable candidates and improve transplantation outcomes among older adults. METHODS: Between 2012 and 2016, as part of their multi-disciplinary transplant evaluation, 171 patients underwent an initial GA with the study geriatrician, who rated them on a five-point scale from "poor" to "excellent," and presented their cases to multidisciplinary transplant review meetings. Patients were followed until June 1st, 2021. Predictor variables included geriatric recommendation, clinical characteristics, and demographics. Outcomes of interest were mortality, receipt of transplant, and waitlist placement. RESULTS: Compared to patients rated "poor," "marginal," or "fair," we found that patients that the geriatrician recommended as "good" or "excellent" were more likely to be waitlisted and receive a transplant. Favorably rated patients were also less likely to be removed from the waitlist due to becoming medically unfit, meaning worsening medical morbidity, frailty, and cognitive status. CONCLUSION: Including geriatricians to perform GAs as part of the transplant evaluation process can help identify suitable elderly candidates.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

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.

Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

Patient-Reported Barriers to the Prekidney Transplant Evaluation in an At-Risk Population in the United States.

BACKGROUND: Despite our knowledge of barriers to the early stages of the transplant process, we have limited insight into patient-reported barriers to the prekidney transplant medical evaluation in populations largely at-risk for evaluation failure. METHODS: One-hundred consecutive adults were enrolled at an urban, Midwestern transplant center. Demographic, clinical, and quality of life data were collected prior to patients visit with a transplant surgeon/nephrologist (evaluation begins). Patient-reported barriers to evaluation completion were collected using the Subjective Barriers Questionnaire 90-days after the initial medical evaluation appointment (evaluation ends), our center targeted goal for transplant work-up completion. RESULTS: At 90 days, 40% of participants had not completed the transplant evaluation. Five barrier categories were created from the 85 responses to the Subjective Barriers Questionnaire. Patient-reported barriers included poor communication, physical health, socioeconomics, psychosocial influences, and access to care. In addition, determinants for successful evaluation completion included being of white race, higher income, free of dialysis, a lower comorbid burden, and reporting higher scores on the Kidney Disease Quality of Life subscale role-emotional. CONCLUSION: Poor communication between patients and providers, and among providers, was the most prominent patient-reported barrier identified. Barriers were more prominent in marginalized groups such as ethnic minorities and people with low income. Understanding the prevalence of patient-reported barriers may aid in the development of patient-centered interventions to improve completion rates.

Urinary-cell mRNA profile and acute cellular rejection in kidney allografts.

BACKGROUND: The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. METHODS: We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. RESULTS: A three-gene signature of 18S ribosomal (rRNA)-normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operating-characteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer-Lemeshow test indicated good fit (P=0.77). In an external-validation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P=0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti-interleukin-2 receptor antibodies from those who received T-cell-depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P=0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). CONCLUSIONS: A molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts. (Funded by the National Institutes of Health and others.).

Determinants of frequent Internet use in an urban kidney transplant population in the United States: characterizing the digital divide.

CONTEXT: The Internet is a staple of electronic communication and is essential to the emerging telemonitoring and health information technology interventions for adults with chronic diseases. OBJECTIVE: To identify determinants of frequent Internet use in an urban kidney transplant population in the United States. DESIGN: A single center, cross-sectional survey study. SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant and 177 posttransplant patients. MAIN OUTCOME MEASURES: Frequent Internet use, defined as using the Internet more than 5 hours per week. RESULTS: Only 38% of participants reported being frequent Internet users. Non-Hispanic blacks and participants who reported their race/ethnicity as "other" were significantly less likely than whites to report being frequent Internet users. Women were 59% less likely than men to be frequent users of the Internet. Those who reported having kidney disease for more than 3 years were more likely to report being frequent Internet users. As education increased, Internet use increased. As age increased, Internet use decreased. CONCLUSION: Alternatives to electronic information sources and/or additional resources should be considered for those who may fall in the so-called digital divide.

Kidney transplant and the digital divide: is information and communication technology a barrier or a bridge to transplant for African Americans?

CONTEXT: Barriers to kidney transplant for African Americans are well documented in the literature. Little information on ownership of information and communication technology and use of such technology in transplant populations has been published. OBJECTIVE: To characterize racial differences related to ownership and use of information and communication technology in kidney transplant patients. DESIGN: A single-center, cross-sectional survey study. SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant patients and 177 transplant recipients. MAIN OUTCOMES MEASURES: The survey consisted of 6 demographic questions, 3 disease-related questions, and 9 technology-related questions. Dichotomous (yes/no) and Likert-scale items were the basis for the survey. RESULTS: Cell phone use was high and comparable between groups (94% in African Americans, 90% in whites, P= .22). A vast majority (75% of African Americans and 74% of whites) reported being "comfortable" sending and receiving text messages. Computer ownership (94.3% vs 79.3%) and Internet access (97.7% vs 80.7%) were greater among whites than African Americans (both P< .01). Fewer African Americans were frequent users of the Internet (27.1% vs 56.3%) and e-mail (61.6% vs 79.3%) than whites (both P<.01). More African Americans than whites preferred education in a classroom setting (77% vs 60%; P< .005) and educational DVDs (66% vs 46%; P< .002). CONCLUSION: The use of cell phone technology and text messaging was ubiquitous and comparable between groups, but computer and Internet access and frequency of use were not. Reaching out to the African American community may best be accomplished by using cell phone/text messaging as opposed to Internet-based platforms.

Physician Preferences when Selecting Candidates for Lower-Quality Kidney Offers.

BACKGROUND: In the United States, more than 50% of kidneys in the lowest 15% quality range (those with Kidney Donor Profile Index >85) are discarded. Studies suggest that using more of these kidneys could benefit patients waiting for a transplant. This study assesses the trade-offs physicians make when selecting recipients for lower-quality kidneys. METHODS: A discrete choice experiment (DCE) was administered to surgeons and nephrologists in the United States who are involved in kidney acceptance decisions. The DCE presented kidneys that varied in terms of Kidney Donor Profile Index, expected cold ischemia time, donor age, pump parameters, serum creatinine levels, glomerulosclerosis, donor diabetes status, and whether donation was made after circulatory death. Candidate characteristics included recipients' age, diabetes history, time on dialysis, ejection fraction, HLA mismatch, calculated panel reactive antibody, and Karnofsky performance score. Regression analysis was used to estimate acceptability weights associated with kidney and recipient characteristics. RESULTS: A total of 108 physicians completed the DCE. The likelihood of acceptance was significantly lower with deterioration of kidney quality, expected cold ischemia time at transplantation, and missing biopsy and pump information. Acceptance was prioritized for patients who were higher on the waiting list, younger recipients, those who have spent less time on dialysis, and those without a history of diabetes. Performance status (Karnofsky score) and calculated panel reactive antibody also had a statistically significant but smaller association. Finally, ejection fraction had a marginally significant association, and HLA match had no significant association with the acceptance of marginal kidneys. A group of respondents were found to be primarily concerned about cold ischemia time. CONCLUSIONS: In this DCE, physicians considered the recipient characteristics that inform expected post-transplant survival score when they decided whether to accept a marginal kidney for a given recipient.

The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.

A simulation-based curriculum can be used to teach open intestinal anastomosis.

BACKGROUND: Simulation is a technique commonly used to teach technical skills such as those necessary in laparoscopic surgery. Curricula with objective, validated metrics rating performance are widely used. Simulations to develop and assess skills necessary for open surgical procedures are less common. We hypothesized that a curriculum designed to teach the skills necessary to perform open laparotomy and bowel anastomosis would result in improved knowledge of the procedure steps, increased technical skills, and improved confidence in novice surgeons. METHODS: A simulation-based curriculum designed to teach open laparotomy and bowel anastomosis was developed. Eleven surgical interns participated in the 6-wk curriculum. Written surveys regarding confidence in the knowledge and ability to perform these procedures were administered before and after the curriculum. Videos of the first six subjects were created on the first and final repetition of the simulation. An Objective Assessment of Technical Skills (OSATS) instrument was used to evaluate each video by two independent, blinded reviewers. RESULTS: Subjects demonstrated significantly improved OSATS scores for skills and knowledge in seven of nine domains assessed upon completion of the curriculum. Subject confidence in laparotomy and bowel anastomosis skills improved significantly. CONCLUSION: A structured, simulation-based curriculum designed to teach laparotomy and hand-sewn bowel anastomosis skills is effective and increases participant confidence. Further study is required to determine whether simulation results in improved performance in the operating room.

Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients.

INTRODUCTION: We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9). METHODS: This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs. RESULTS: Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%. CONCLUSIONS: Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary.

Patient and Clinician Perceptions of Informed Consent and Decision Making About Accepting KDPI > 85 Kidneys.

BACKGROUND: Although the impact of the kidney donor profile index (KDPI) on kidney discard is well researched, less is known about how patients make decisions about whether to give consent for KDPI > 85 kidney offers. METHODS: We conducted in-depth, semistructured interviews with 16 transplant recipients, 15 transplant candidates, and 23 clinicians (transplant surgeons, nephrologists, and nurse coordinators) to assess and compare perceptions of transplant education, informed consent for KDPI > 85 kidneys' and the decision-making process for accepting kidney offers. Thematic analysis was used to analyze qualitative data. RESULTS: Four themes emerged: (1) patients reported uncertainty about the meaning of KDPI or could not recall information about KDPI; (2) patients reported uncertainty about their KDPI > 85 consent status and a limited role in KDPI > 85 consent decision making; (3) patients' reported willingness to consider KDPI > 85 kidneys depended on their age, health status, and experiences with dialysis, and thus it changed over time; (4) patients' underestimated the survival benefit of transplantation compared with dialysis, which could affect their KDPI > 85 consent decision making. CONCLUSIONS: To better support patients' informed decision making about accepting KDPI > 85 kidneys, centers must ensure that all patients receive education about the trade-offs between accepting a KDPI > 85 kidney and remaining on dialysis. Additionally, education about KDPI and discussions about informed consent for KDPI > 85 kidneys must be repeated at multiple time points while patients are on the waiting list.

The Role of Procurement Biopsies in Kidney Acceptance Decision Making and Kidney Discard: Perceptions of Physicians, Nurse Coordinators, and OPO Staff and Directors.

Procurement biopsies suffer from challenges with quality and reproducibility and are linked to kidney discard. Nonetheless, procurement biopsies are obtained for the majority of kidneys in the United States, and biopsy findings are commonly relied upon in kidney acceptance decisions. Methods: We conducted in-depth, semistructured interviews with 30 surgeons, nephrologists, nurse coordinators, and organ procurement organization (OPO) staff and directors to assess perceptions of factors contributing to kidney discard and strategies to reduce kidney discard, with a focus on the role of procurement biopsies. Thematic analysis was used to analyze qualitative data. Results: Three main themes emerged: (1) participants emphasized the importance of biopsy findings in making acceptance decisions but expressed concerns about a lack of standardization and quality control; (2) participants reported large variations in the level of importance placed on biopsy findings, the level of reliance on glomerulosclerosis in particular, and the cutoffs used; and (3) participants disagreed about how often procurement biopsies should be taken, with some supporting stricter limits on which kidneys are biopsied and others preferring a biopsy for most kidney offers. Conclusions: These findings support the development of standard practices for which kidneys require biopsy, how the biopsy material is prepared, and how the biopsy is interpreted. Variability in kidney acceptance practices across centers and the use of biopsy findings in guiding recipient selection also lend support to policies to allocate kidneys with suboptimal histological findings to the centers that are willing to use such kidneys and the patients who could most benefit from such offers.

Knowledge and attitudes regarding colorectal cancer screening among medical students: a tale of two schools.

Colorectal cancer (CRC) screening has been shown to decrease the incidence of CRC cancers and decrease mortality. Studies show that the most important predictor of patient compliance with CRC screening is physician recommendation. We assessed the knowledge and attitudes of medical students regarding cancer screening. A study-specific questionnaire was distributed to medical students (MS) at two medical schools. There was a significant difference in the percentage of correctly answered questions regarding screening recommendations between first year MS and all other years for both schools. However, MS attitudes towards CRC screening were consistent between classes and schools. Although most MS had positive attitudes regarding cancer screening our survey identified several important deficits in knowledge.