Evaluation of adult kidney transplant candidates

Important advances in immunosuppressive therapy and refinement in surgical techniques have allowed renal transplantation to become the treatment of choice for virtually all suitable candidates with end-stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life and, over time, can reduce the total cost of medical care. It must be noted, however, that although the risk of death in the first year after transplantation is <5%, not all patients qualify for the surgery because of their unacceptable risks for complications. The transplant evaluation process requires a comprehensive assessment of each patient's medical, surgical, and psychosocial histories. Selection of the suitable transplant candidate remains a challenge for transplant physicians owing, predominantly, to the presence of complex medical issues in the potential candidates and nonstandardized criteria for acceptance or rejection among transplant centers. Furthermore, with the ever-increasing disparity between donor organ supply and demand and resultant increased wait-list times, the transplant physicians must further consider the optimal management and re-evaluation of wait-list patients during the waiting period. This article describes a systematic approach for the evaluation of a potential renal transplant candidate. Various medical issues that arise during the evaluation process are discussed.     

Home monitoring for lung transplant candidates

Home monitoring by lung transplant recipients has been effective for early detection of clinical problems. This study used an electronic diary for home monitoring by lung transplant candidates to improve communication between candidates and the transplant team. Candidates were randomized into control (52 subjects following standard telephone reporting procedures) and intervention (67 subjects using an electronic diary to record and transmit a range of health-related measures) groups. Outcome measures were monitoring adherence and level of communication (for monitor acceptability and utilization), hospital length of stay after transplantation and survival at 4 months (for clinical effectiveness). Subjects used the diary without difficulty and with good adherence. Subjects and coordinator contacts were similar between groups; intervention group subjects were positive regarding contact based on diary use. There were no significant differences in clinical outcomes between groups. Changing diary questions might improve the effectiveness of electronic monitoring for lung transplant candidates.     

A nonlinear relationship between visceral adipose tissue and frailty in adult lung transplant candidates

Frailty is a state of decreased physiologic reserve associated with poor outcomes before and after lung transplantation. Obesity, particularly central obesity characterized by excess proinflammatory visceral adipose tissue (VAT), is associated with incident frailty in middle‐aged and older adults. The association between VAT and frailty in advanced lung disease, however, is unknown. In two, nonoverlapping multicenter cohorts of adults listed for lung transplantation, we measured VAT area on bioelectrical impedance assay (BIA) in one cohort and cross‐sectional VAT and subcutaneous adipose tissue (SAT) areas on abdominal computed tomography (CT) in the other. We identified a nonlinear relationship between greater VAT by BIA and frailty. In fully adjusted piecewise regression models, every 20 cm² increase in VAT area was associated with 50% increased odds of frailty in subjects with high VAT (95% CI 1.2‐1.9, P < .001), and 10% decreased odds of frailty (95% CI 0.7‐1.04, P = .12) in subjects with low VAT. Compared to frail subjects with low VAT, those with high VAT were more likely to have low grip strength and less likely to have weight loss, suggesting that mechanisms of frailty may differ by VAT. Further investigation of mechanisms linking VAT and frailty may identify new targets for prevention and treatment.     

Dental health status of liver transplant candidates.

A prerequisite dental evaluation is usually recommended for potential organ transplant candidates. This is based on the premise that untreated dental disease may pose a risk for infection and sepsis, although there is no evidence that this has occurred in organ transplant candidates or recipients. The purpose of this study was to assess the prevalence of dental disease and oral health behaviors in a sample of liver transplant candidates (LTCs). Oral examinations were conducted on 300 LTCs for the presence of gingivitis, dental plaque, dental caries, periodontal disease, edentulism, and xerostomia. The prevalence of these conditions was compared with oral health data from national health surveys and examined for possible associations with most recent dental visit, smoking, and type of liver disease. Significant risk factors for plaque-related gingivitis included intervals of more than 1 yr since the last dental visit (P = 0.004), smoking (P = 0.03), and diuretic therapy (P = 0.005). Dental caries and periodontal disease were also significantly associated with intervals of more than 1 yr since the last dental visit (P = 0.004). LTCs with viral hepatitis or alcoholic cirrhosis had the highest smoking rate (78.8%). Higher rates of edentulism occurred among older LTCs who were less likely to have had a recent dental evaluation (mean 88 months). In conclusion, intervals of more than 1 yr since the last dental visit, smoking, and diuretic therapy appear to be the most significant determinants of dental disease and the need for a pretransplantation dental screening evaluation in LTCs. Edentulous patients should have periodic examinations for oral cancer.     

Treatment of hepatitis C in potential lung transplant candidates

International guidelines list hepatitis C virus (HCV) as a contraindication to lung transplant (LTx). Since the development of these guidelines, the natural history of HCV after nonhepatic transplant has been clarified, and more effective antiviral therapy is available. In renal transplant candidates, HCV treatment before transplantation improves posttransplant outcome. There are no data regarding the safety and efficacy of HCV therapy in LTx candidates. We describe the outcomes of HCV treatment in five LTx candidates. Three have had a sustained virologic response and there have been no unexpected adverse effects. Two have gone on to LTx. We conclude that selected lung transplant candidates can safely and effectively be treated for HCV before transplantation. An approach to selecting HCV-positive LTx candidates for antiviral therapy and transplant listing using clinical, virologic, and histologic data is described based on this experience and current knowledge regarding HCV natural history after solid organ transplant.     

Diagnostic yield of screening colonoscopies in lung transplant candidates

BACKGROUND: Colonoscopy has been used to screen lung transplant candidates for colorectal diseases that would preclude transplantation. The diagnostic yield of this procedure is unknown. METHODS: This is a retrospective cohort study of patients 50 years of age and over who underwent lung transplant evaluations from 1996 to 1999. We assessed the prevalence and location of colonoscopic abnormalities, the predictive value of risk factors for colonic neoplasms, and the impact of colonoscopic findings on management. RESULTS: Thirty-one patients were evaluated. Twenty-four patients had at least one abnormal endoscopic finding. Six patients (19%) had adenomatous polyps; no carcinomas were detected. The 13 patients with risk factors were more likely to have adenomas (relative risk=2.8, P=0.2). The negative predictive value of risk factors for adenomas was 89%. One patient's management was altered and none were denied transplant listing because of the colonoscopic findings. CONCLUSIONS: Screening colonoscopy did not substantively alter the management of lung transplant candidates. More selective screening strategies may be warranted.     

Life expectancy without a transplant for status 1A liver transplant candidates

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using Scientific Registry of Transplant Recipients data from all prevalent liver transplant candidates from 2010 to 2020, we used a bias-corrected Kaplan–Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20–46) days—over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.     

Osteoporosis in lung transplant candidates compared to matched healthy controls

Lakey WC, Spratt S, Vinson EN, Gesty‐Palmer D, Weber T, Palmer S. Osteoporosis in lung transplant candidates compared to matched healthy controls.
Clin Transplant 2011: 25: 426–435. © 2010 John Wiley & Sons A/S. Abstract: Purpose: Advanced lung disease increases the risk for diminished bone mineral density (BMD). The prevalence and severity of osteoporosis in lung transplant candidates is unclear. Methods: We retrospectively evaluated BMD of subjects screened for lung transplant at our institution. Observed prevalence of osteoporosis and osteopenia within our cohort was compared to the expected prevalence of each from the Third National Health and Nutrition Examination Survey (NHANES III) data matched for age, gender, and race. Lateral chest radiographs were evaluated for vertebral fractures. Results: High prevalence rates of osteoporosis (37%) and combined osteoporosis/osteopenia (86%) were observed. Subjects with pulmonary fibrosis had higher BMD and T‐scores compared to all other subgroups. All subjects within the cohort had a higher observed combined rate of osteoporosis/osteopenia at all bone sites compared to expected rates from healthy, matched controls. Vertebral fractures were present in 23% of subjects but did not correlate with BMD or the diagnosis of osteoporosis. Conclusions: Abnormal BMD was prevalent in most pre‐lung transplant subjects, with striking differences noted in comparison with a healthy, matched cohort. Lateral chest radiographs in combination with BMD data give a more complete picture of bone abnormalities. Osteoporosis screening prior to lung transplantation should be performed to identify high‐risk subjects for fracture and allow for intervention.     

Tobacco and alcohol use in lung transplant candidates and recipients

Tobacco and alcohol use among lung transplant candidates and recipients is unknown. Our first goal was to describe tobacco and alcohol use before and after lung transplant in patients with cystic fibrosis (CF) and other pulmonary diseases (non-CF). Our second goal was to determine whether demographic variables, depression, anxiety and social support predicted tobacco and alcohol use. Self-report data from transplant candidates and recipients, and transplant nurse coordinator ratings of post-transplant smoking and drinking were utilized. Data from two samples were analyzed. Sample 1 comprised 219 patients being evaluated for lung transplant, and sample 2 comprised 45 transplant recipients who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated that 72% of non-CF patients and 16% of CF patients had a history of smoking cigarettes, and the majority of patients in both groups had consumed alcohol in the past. For CF patients, past smoking was related to higher depression scores, and past drinking was related to higher education and lower social support. For non-CF patients, a history of smoking was associated with being Caucasian and older. For CF patients, a history of drinking was associated with being older and less depressed, and for non-CF patients a history of drinking was associated with higher education and lower social support. Post-transplant 100% of recipients reported abstinence from tobacco, and over 60% reported abstinence from alcohol. Transplant coordinator ratings corroborated that no transplant recipients were using tobacco products or consuming alcohol in an excessive or problematic manner. For both groups, consuming alcohol after transplant was related to lower levels of social support. In conclusion, lung recipients remain abstinent from tobacco, and although over 30% of patients consume alcohol after transplant, it is not at problematic levels. Smoking and drinking behaviors were related to demographic variables, depression, and low social support.     

Multiple listing in lung transplant candidates: A cohort study

Lung transplant candidates can be waitlisted at more than one transplant center, a practice known as multiple listing. The factors associated with multiple listing and whether multiple listing modifies waitlist mortality or likelihood of lung transplant is unknown. US lung transplant waitlist candidates were identified as either single or multiple listed using data from the Scientific Registry of Transplant Recipients. Characteristics of single and multiple listed candidates were compared and multivariable logistic regression was used to estimate associations with multiple listing. Multiple listed candidates were matched to single listed candidates using a combination of exact and propensity score matching methods. Cox proportional hazard models were used to estimate the relationship of multiple listing on waitlist mortality and receiving a transplant. Multiple listing occurred in 2.3% of lung transplant waitlist candidates. Younger age, female gender, white race, short stature, high antibody sensitization, college or postcollege education, lower lung allocation score, and a cystic fibrosis diagnosis were independently associated with multiple listing. Multiple listing was associated with an increased likelihood of lung transplant (adjusted hazard ratio [aHR] 2.74, 95% CI 2.37 to 3.16) but was not associated with waitlist mortality (aHR 0.99, 95% CI 0.68 to 1.44).     

Measles outbreak risk assessment for transplant candidates and recipients

Solid organ transplant (SOT) candidates and recipients are at risk of significant morbidity and mortality from infection, including those circulating in the community from unexpected outbreaks. In late 2018-summer of 2019, a measles outbreak occurred in the New York City area, with a total of 649 cases reported. We developed a systematic 3-part approach to address measles risk in our adult SOT program through: (a) identification of nonimmune adults living in outbreak ZIP codes, (b) education focused on risk reduction for patients from outbreak ZIP codes, and (c) risk reduction for nonimmune patients. All waitlisted or previously transplanted patients residing in outbreak areas received a measles patient education handout. The electronic medical record of patients born in or after 1957 was reviewed for serologic evidence of measles immunity. Measles immunity testing was performed in patients without documentation of immunity. Patients who tested nonimmune were offered MMR vaccination or intravenous immunoglobulin depending on their transplant phase and risk profile. Thus, we demonstrate successful implementation of a systematic risk assessment during a large measles outbreak to identify and protect at-risk SOT patients. As vaccine hesitancy persists, our strategies may be increasingly relevant to transplant centers and those caring for immunocompromised patients.     

Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates

Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3⁺, CD3⁺/CD4⁺, CD3⁺/CD8⁺ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.