Kidney Transplant Clinicians' Perceptions of Palliative Care for Patients With Failing Allografts in the US: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN: National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS: Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH: Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS: A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS: Potential selection bias. CONCLUSIONS: Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY: Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

The association of center volume with transplant outcomes in selected high-risk groups in kidney transplantation.

BACKGROUND: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. METHODS: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000-2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m2, receiving kidneys from donors with kidney donor profile index(KDPI) ≥ 85%, acute kidney injury(AKI), hepatitisC + . Average annual CV for the specific-high-risk KT categorized in tertiles. Death-Censored-Graft-Loss(DCGL) and death at 3 months, 1, 5, and 10 years were compared between CV tertiles using Cox-regression models. RESULTS: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m2 had higher risk of DCGL in low CV(aHR = 1.11,95%CI = 1.03-1.19) at 10 years; recipients with age ≥ 70 years had higher risk of death in low CV(aHR = 1.07,95%CI = 1.01-14) at 10 years. There was no difference of DCGL or death in low CV for donors with KDPI ≥ 85%, hepatitisC + , or AKI. CONCLUSIONS: Recipients of high-risk KT with BMI ≥ 35 kg/m2 have higher risk of DCGL and recipients age ≥ 70 years have higher risk of death in low CV, compared to high CV. Future studies should identify care practices associated with CV that support optimal outcomes after KT.

Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study.

The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.

Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%-22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased-donor kidney transplant [DDKA], living-donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, 95%CI: 0.70-0.95) less graft survival time and 18% (TR 0.82, 95%CI: 0.68-0.97) less patient survival time, DDKA had 23% (TR 0.77, 95%CI: 0.68-0.87) less graft survival time and 29% (TR 0.71, 95%CI: 0.62-0.81) less patient survival time, and SPK with early pancreas graft loss had 34% (TR 0.66, 95%CI: 0.56-0.78) less graft survival time and 34% (TR 0.66, 95%CI: 0.55-0.79) less patient survival time. In conclusion, SPK,P+ recipients have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone.

Corrigendum: Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

[This corrects the article DOI: 10.3389/ti.2022.10618.].

CAR-T therapy in solid organ transplant recipients with treatment refractory posttransplant lymphoproliferative disorder.

Chimeric antigen receptor T cells (CAR-T) are genetically modified T cells with a chimeric antigen receptor directed against a specific tumor-associated antigen like CD19 in lymphoma. CAR-T cells have shown encouraging activity against recurrent and refractory diffuse large B cell lymphomas (DLBCL). However concurrent use of immunosuppressive agents was prohibited in most CAR-T trials effectively excluding patients with prior solid organ transplantation (SOT) and posttransplant lymphoproliferative disorders (PTLD). We report the outcomes for three patients with PTLD refractory to immunochemotherapy 10-20 years after SOT who received CAR-T therapy between January 2018 and December 2019. One patient had an orthotopic heart transplant, the second had a deceased donor kidney transplant, and the third had a pancreas after kidney transplant (PAK). All patients developed complications of CAR-T therapy such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and acute kidney injury requiring renal replacement therapy in the two out of three patients. All patients expired after withdrawal of care due to lack of response to CAR-T therapy. In addition, the PAK patient developed acute pancreatitis after CAR-T therapy. This case series identifies the challenges of using CAR-T therapy to manage refractory PTLD in SOT recipients and its possible complications.

Outcomes of palliative care consultation in patients with ESRD who received cardiopulmonary resuscitation.

BACKGROUND: The majority of dialysis patients receive aggressive burdensome treatment near the end of life. Currently, we lack interventions to improve end-of-life care (EoLC) for these patients. We examined the association of palliative care consultation with improving EoLC for critically ill patients with end-stage renal disease (ESRD) who received cardiopulmonary resuscitation (CPR). MATERIALS AND METHODS: In this retrospective study, we included patients with ESRD admitted to a large academic center who received CPR either prior to or during their hospital stay. Over 8 years, 17 out of 403 patients received palliative care consultation during their hospital stay; consultations were not standardized in their content. Main outcomes of interest to operationalize better EoLC were: (1) change in code status from full code to do not resuscitate (DNR) and (2) withdrawal from intensive care. RESULTS: Of the patients studied, 60.5% were African-American and 43.2% were female. Demographic differences between those with palliative care consultation and those with usual care were not statistically significant. Palliative care consultation was associated with higher odds of change in code status to DNR (odds ratio 8.10, 95% confidence interval 2.19 - 29.94) and withdrawal from intensive care (odds ratio 8.82, 95% confidence interval 2.69 - 28.91) in patients with ESRD who had received CPR. Palliative care consultation was not associated with any change in in-hospital mortality. CONCLUSION: Palliative care consultation needs to be considered for hospitalized ESRD patients with limited expected prognoses as it may reduce aggressive and burdensome therapies at the end of life. Furthermore, primary palliative care skills such as communication and decision-making should be taught to nephrologists to improve EoLC for dialysis patients.

Patients' perspectives on dialysis decision-making and end-of-life care
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BACKGROUND: Few studies have explored dialysis patients' perspectives on dialysis decision-making and end-of-life-care (EoLC) preferences. We surveyed a racially diverse cohort of maintenance dialysis patients in the Cleveland, OH, USA, metropolitan area. MATERIALS AND METHODS: In this cross-sectional study, we administered a 41-item questionnaire to 450 adult chronic dialysis patients. Items assessed patients' knowledge of their kidney disease as well as their attitudes toward chronic kidney disease (CKD) treatment issues and EoLC issues. RESULTS: The cohort included 67% Blacks, 27% Caucasians, 2.8% Hispanics, and 2.4% others. The response rate was 94% (423/450). Most patients considered it essential to obtain detailed information about their medical condition (80.6%) and prognosis (78.3%). Nearly 19% of respondents regretted their decision to start dialysis. 41% of patients would prefer treatment(s) aimed at relieving pain rather than prolonging life (30.5%), but a majority would want to be resuscitated (55.3%). Only 8.4% reported having a designated healthcare proxy, and 35.7% reported completing a living will. A significant percentage of patients wished to discuss their quality of life (71%), psychosocial and spiritual concerns (50.4%), and end-of-life issues (38%) with their nephrologist. CONCLUSION: Most dialysis patients wish to have more frequent discussions about their disease, prognosis, and EoLC planning. Findings from this study can inform the design of future interventions.
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Nosocomial infections in the ICU: Pens and spectacles as fomites.

Nosocomial infections are a major cause of morbidity and mortality. Non-medical objects known as fomites may have a role in their genesis. We investigated the significance of writing pens and spectacles as fomites. The study was conducted at Aga Khan University Hospital, Karachi, from July 2013 to September 2013. Cultures were taken from pens and/or spectacles of resident nurses, doctors and nursing assistants in intensive care unit (ICU). Organisms important in ICU nosocomial infections were targeted. Seven rounds of sampling over 3 weeks led to 55 pen and 5 spectacle samples. Growth was seen in 3(5.5%) pen samples and 1(20%) spectacle sample. Two (3.6%) pen cultures grew acinetobacter, 1)1.8%) grew candida and acinetobacter, and i spectacle culture grew vancomycin-resistant enterococcus faecium (VRE). Two out of the 4 (50%) personnel managing all ICU beds had growth. During the study, one or more ICU patients had infection with the same organisms. Pens and spectacles may be responsible for the spread of organisms like acinetobacter and VRE. Personnel managing multiple beds are more likely to carry contaminated fomites.

Medical and Surgical Management of the Failed Pancreas Transplant.

Despite the continued improvements in pancreas transplant outcomes in recent decades, a subset of recipients experience graft failure and can experience substantial morbidity and mortality. Here, we summarize what is known about the failed pancreas allograft and what factors are important for consideration of retransplantation. The current definition of pancreas allograft failure and its challenges for the transplant community are explored. The impacts of a failed pancreas allograft are presented, including patient survival and resultant morbidities. The signs, symptoms, and medical and surgical management of a failed pancreas allograft are described, whereas the options and consequences of immunosuppression withdrawal are reviewed. Medical and surgical factors necessary for successful retransplant candidacy are detailed with emphasis on how well-selected patients may achieve excellent retransplant outcomes. To achieve substantial medical mitigation and even pancreas retransplantation, patients with a failed pancreas allograft warrant special attention to their residual renal, cardiovascular, and pulmonary function. Future studies of the failed pancreas allograft will require improved reporting of graft failure from transplant centers and continued investigation from experienced centers.

Outcomes Following In-Hospital Cardiopulmonary Resuscitation in People Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: Previous studies showing poor cardiopulmonary resuscitation (CPR) outcomes in the dialysis population have largely been derived from claims data and are somewhat limited by a lack of detailed characterization of CPR events. We aimed to analyze CPR-related outcomes in individuals receiving maintenance dialysis. STUDY DESIGN: Retrospective chart review. SETTING & PARTICIPANTS: Using electronic medical records from a single academic health care system, we identified all hospitalized adult patients receiving maintenance dialysis who had undergone in-hospital CPR between 2006 and 2014. EXPOSURE: Initial in-hospital CPR. OUTCOMES: Overall survival, predictors of unsuccessful CPR, predictors of death during the same hospitalization among initial survivors, predictors of discharge-to-home status. ANALYTICAL APPROACH: We provide descriptive statistics for the study variables and used t tests, χ2 tests, or Fisher exact tests to compare differences between the groups. We built multivariable logistic regression models to examine the CPR-related outcomes. RESULTS: A total of 184 patients received in-hospital CPR: 51 (28%) did not survive the initial CPR event, and 77 CPR survivors died (additional 42%) later during the same hospitalization (overall mortality 70%). Only 18 (10%) were discharged home, with the remaining 32 (17%) discharged to a rehabilitation facility or a nursing home. In the multivariable model, the only predictor of unsuccessful CPR was CPR duration (OR, 1.41; 95% CI, 1.24-1.61; P < 0.001). Predictors of death during the same hospitalization after surviving the initial CPR event were CPR duration (OR, 1.15; 95% CI 1.04-1.27; P = 0.007) and older age (OR, 1.64; 95% CI, 1.23-2.2; P < 0.001). Older people also had lower odds of discharge-to-home status (OR, 0.25; 95% CI, 0.11-0.54; P < 0.001). LIMITATIONS: Retrospective study design, single-center study, no information on functional status. CONCLUSIONS: Patients receiving maintenance dialysis experience high mortality following in-hospital CPR and only 10% are discharged home. These data may help clinicians provide useful prognostic information while engaging in goals of care conversations.

Association of Ambient Fine Particulate Matter Air Pollution With Kidney Transplant Outcomes.

Importance: Increased levels of ambient fine particulate matter (PM2.5) air pollution are associated with increased risks for detrimental health outcomes, but risks for patients with kidney transplants (KTs) remain unknown. Objective: To investigate the association of PM2.5 exposure with KT outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted using data on patients who received KTs from 2004 to 2016 who were identified in the national US transplant registry and followed up through March 2021. Multiple databases were linked to obtain data on PM2.5 concentration, KT outcomes, and patient clinical, transplant, and contextual factors. Data were analyzed from April 2020 through July 2021. Exposures: Exposures included post-KT time-dependent annual mean PM2.5 level (in 10 µg/m3) and mean PM2.5 level in the year before KT (ie, baseline levels) in quartiles, as well as baseline annual mean PM2.5 level (in 10 µg/m3). Main Outcomes and Measures: Acute kidney rejection (ie, rejection within 1 year after KT), time to death-censored graft failure, and time to all-cause death. Multivariable logistic regression for kidney rejection and Cox analyses with nonlinear assessment of exposure-response for death-censored graft failure and all-cause death were performed. The national burden of graft failure associated with PM2.5 levels greater than the Environmental Protection Agency recommended level of 12 µg/m3 was estimated. Results: Among 112 098 patients with KTs, 70 522 individuals (62.9%) were older than age 50 years at the time of KT, 68 117 (60.8%) were men, and the median (IQR) follow-up was 6.0 (3.9-8.9) years. There were 37 265 Black patients (33.2%), 17 047 Hispanic patients (15.2%), 48 581 White patients [43.3%]), and 9205 patients (8.2%) of other race or ethnicity. The median (IQR) baseline PM2.5 level was 9.8 (8.3-11.9) µg/m3. Increased baseline PM2.5 level, compared with quartile 1 baseline PM2.5 level, was not associated with higher odds of acute kidney rejection for quartile 2 (adjusted odds ratio [aOR], 0.99; 95% CI, 0.92-1.06) but was associated with increased odds for quartile 3 (aOR, 1.11; 95% CI, 1.04-1.20) and quartile 4 (aOR, 1.13; 95% CI, 1.05-1.23). Nonlinear assessment of exposure-response for graft failure and death showed no evidence for nonlinearity. Increased PM2.5 levels were associated with increased risk of death-censored graft failure (adjusted hazard ratio [aHR] per 10 µg/m3 increase, 1.17; 95% CI, 1.09-1.25) and all-cause death (aHR per 10 µg/m3 increase, 1.21; 95% CI, 1.14-1.28). The national burden of death-censored graft failure associated with PM2.5 above 12 µg/m3 was 57 failures (95% uncertainty interval, 48-67 failures) per year among patients with KTs. Conclusions and Relevance: This cohort study found that PM2.5 level was an independent risk factor associated with acute rejection, graft failure, and death among patients with KTs. These findings suggest that efforts toward decreasing levels of PM2.5 concentration may be associated with improved outcomes after KT.

Efficacy and Safety of Tocilizumab in the Treatment of Acute Active Antibody-mediated Rejection in Kidney Transplant Recipients.

Antibody-mediated rejection (AMR) continues to have a deleterious impact on kidney allograft survival. Recent evidence supports use of tocilizumab for treatment of chronic active AMR, but it has not been assessed for treatment of acute active AMR. METHODS: We performed a single-center, observational study of kidney transplant recipients who received at least 1 dose of tocilizumab in addition to conventional therapies for acute active AMR between October 2016 and October 2018 with follow-up through August 2019. RESULTS: Seven patients were included. All 7 patients received tocilizumab 8 mg/kg (max dose, 800 mg) monthly. We noted a 50% or greater reduction in immunodominant donor-specific antibodies in 4 of 6 patients. Renal function improved or stabilized in all patients throughout the duration of therapy. One patient developed cytomegalovirus esophagitis and 1 had a potential hypersensitivity reaction. In the extended follow-up, 1 patient had mixed rejection and 2 patients had T-cell-mediated rejection, which occurred 6 to 24 mo after completion of therapy. CONCLUSIONS: Tocilizumab may be considered as an addition to conventional therapies for treatment of acute active AMR. More studies are needed to determine which patients may benefit from therapy and to examine the appropriate duration of treatment.