Transplant tourism to China: the impact on domestic patient‐care decisions

Abstract: Organ procurement in China has been criticized because of its reliance on executed prisoners as donors. We aimed to assess the influence of perceptions about organ procurement practices in China on domestic patient‐care decisions. Methods: An anonymous internet administered case‐based questionnaire was used to survey a sample of healthcare professionals with affiliations to hepatology and transplantation professional societies. Results: Of 674 completed surveys, the vast majority (93%) of the respondents were physicians, surgeons or allied transplant professionals actively caring for liver transplant patients and 81% practiced in the US. A strong majority believed procurement practices were ethically sound in the US and Europe (87% and 73%) but fare fewer believed that procurement practices were ethically sound in China (4%, p < 0.001). In case‐based questions, lack of confidence in the ethical standards of organ procurement in China predicted patient‐care decisions. The majority would provide post‐transplantation care for patients who underwent liver transplantation at another domestic center, in a foreign country and in China (90%, 78%, and 63%, respectively, p < 0.001) yet respondents who suspected unethical procurement practices in China were more reluctant to do so (p < 0.001). Conclusions: Transplant professionals expressed concern about organ procurement practices in China which influenced their patient‐care decision‐making.     

Agreement of immunosuppression regimens described in Medicare pharmacy claims with the Organ Procurement and Transplantation Network survey

The Organ Procurement and Transplantation Network (OPTN) collects intermittent survey data on immunosuppressive medication use that are studied frequently as research measures. Pharmacy billing claims may provide an accurate measure of immunosuppression use over time. Herein is characterized the agreement of Medicare pharmacy claims for immunosuppressive medications with OPTN reports. Data were drawn from the United States Renal Data System. Participants received a kidney transplant in 2000 to 2001 and had an OPTN record and a Medicare pharmacy claim for an immunosuppressive drug at transplant discharge and 6 mo and 1 yr after transplantation. The concordance (kappa) of the OPTN and claims (+/-30 d of survey) for indicated medication use was compared, and sensitivity, specificity, and predictive values for claims were computed, assuming OPTN as a "gold standard." Clinical trial participation and regimen changes were examined as explanations for discordance. A total of 4357 eligible subjects were identified. Concordance over observation ranged from excellent for calcineurin inhibitors (kappa > 0.86) to generally very good for adjunctive agents (kappa = 0.49 to 0.75) to poor for corticosteroids (kappa <0.15). Claims demonstrated high positive predictive values (> or =97%) but low negative predictive values (< or =13%) for OPTN-reported corticosteroid use. Regimen changes (28 to 75%) but not clinical trial participation (< or =21%) were identified frequently among cases with discordant indications of nonsteroid medication use. Close agreement of Medicare billing claims and the OPTN for indicated use of nonsteroid immunosuppressive medications supports both as useful measures of drug exposure. Low detection rates of OPTN-indicated corticosteroid use within claims require further examination.     

The association between loss of Medicare,immunosuppressive medication use,and kidney transplant outcomes

Kidney transplant recipients aged <65 years qualify for Medicare coverage, but coverage ends 3 years posttransplant. We determined the association between timing of Medicare loss and immunosuppressive medication fills and kidney allograft loss. Using data from the Scientific Registry of Transplant Recipients (SRTR), US Renal Data System, and Symphony pharmacy fill database, we analyzed 78 861 Medicare‐covered, kidney‐alone recipients aged <65 years, and assessed the timing of Medicare loss posttransplant: early (<3 years), on‐time (at 3 years), or late (>3 years). Immunosuppressant use was measured as medication possession ratio (MPR). Allograft loss was assessed using SRTR data. MPR was lower for recipients with early or late Medicare loss compared with no coverage loss for all immunosuppressive medication types. For calcineurin inhibitors, early Medicare loss was associated with a 53% to 86% lower MPR. On‐time Medicare loss was not associated with a lower MPR. When recipients were matched by age, posttransplant timing of Medicare loss, and donor risk, the hazard of allograft loss was 990% to 1630% higher after early Medicare loss, and 140% to 740% higher after late Medicare loss, with no difference in the hazard for on‐time Medicare loss. Ensuring ongoing Medicare access before and after 3 years posttransplant could affect graft survival.     

A cost analysis for transplantation and options post-Medicare

The health care issue related to Medicare coverage of immunosuppressant medications has major implications for the medical professional and transplant recipient. Based on cost containment analysis, transplantation is the least expensive route to treat ESRD and justifies support for these bills in Congress to eliminate the time constraints of Medicare payment of immunosuppressant medications. Members of the renal health care community need to be active in the political arena of health care reformation and present their views to policymakers.     

The effect of an organ procurement experience on preclinical medical student perceptions of transplant surgery

Transplant surgery is a predominantly male specialty with high burnout rates. There are currently limited data regarding how programs can attract a diverse applicant pool to the field of transplant surgery. This study evaluated the effect of an Organ Procurement Experience elective on preclinical medical students' perceptions of transplant surgery in a prospective, longitudinal study. Preclinical medical students were anonymously surveyed before and after attending a deceased donor organ procurement. Questions focused on the following themes: Personal Beliefs, Personal/Professional Life, Diversity, and Gender Equality. Responses were rated on a five‐point Likert scale. Ninety‐nine and 45 students completed pre/post‐procurement survey, respectively. Post‐procurement responses demonstrated increased education about the field (2.1/5 vs 3.89/5, P < 0.001) and perceptions of the personalities and collegiality between surgeons (3.06/5 vs 3.73/5, P = 0.005). Post‐procurement, women were less likely to feel that female transplant surgeons are treated differently (3.98/5 vs. 3.45/5, P < 0.017). Post‐procurement, 19% agreed that transplant surgeons have a high quality of life. One percent of respondents felt the current gender distribution in transplant surgery is satisfactory. The Organ Procurement Experience significantly improved preclinical students’ perceptions of the field. However, there remains a strong concern about quality of life and gender diversity within the field.     

Describing the evolution of medication nonadherence from pretransplant until 3 years post‐transplant and determining pretransplant medication nonadherence as risk factor for post‐transplant nonadherence to immunosuppressives: The Swiss Transplant Cohort Study

Although medication nonadherence (MNA) is a major risk factor for poor outcomes, the evolution of MNA from pre‐ to 3 years post‐transplant among the four major organ transplant groups remains unknown. Therefore, this study described this evolution and investigated whether pretransplant MNA predicts post‐transplant immunosuppressive medication nonadherence (IMNA). Adult participants (single transplant, pretransplant and ≤1 post‐transplant assessment, using medications pretransplant) in the Swiss Transplant Cohort Study (a prospective nation‐wide cohort study) were included. Nonadherence, defined as any deviation from dosing schedule, was assessed using two self‐report questions pretransplant and at 6, 12, 24 and 36 months post‐transplant. Nonadherence patterns were modelled using generalized estimating equations. The sample included 1505 patients (average age: 52.5 years (SD: 13.1); 36.3% females; 924 renal, 274 liver, 181 lung, 126 heart). The magnitude and variability of self‐reported MNA decreased significantly from pretransplant to 6 months post‐transplant (OR = 0.21; 95% CI: 0.16–0.27). Post‐transplant IMNA increased continuously from 6 months to 3 years post‐transplant (OR = 2.75; 95% CI: 1.97–3.85). Pretransplant MNA was associated with threefold higher odds of post‐transplant IMNA (OR = 3.10; 95% CI: 2.29–4.21). As pretransplant MNA predicted post‐transplant IMNA and a continuous increase in post‐transplant IMNA was observed, early adherence‐supporting interventions are indispensible.     

Analysis of hypertension in children post renal transplantation —a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)

Hypertension is common in children after renal transplantation and is associated with multiple factors. Data regarding the prevalence of post-transplant hypertension and the relationship between immunosuppressive drugs and the presistence of hypertension in a large population of North American children have not been available. This study was designed by the North American Pediatric Renal Transplant Cooperative Study to evaluate in a large diverse multicenter population of children the prevalence of hypertension post transplantation, the type of antihypertensive medication used to treat this hypertension and to determinc the relationship between the blood pressure control and the immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70% of recipients required antihypertensive medications 1 month post transplant compared with 48% pre transplant; the incidence decreased to 59% at 24 months; (2) the majority of children received multiple drug therpay to control blood pressure; (3) hypertension can be controlled effectively despite inherent etiological factors, such as allograft source, prior hypertension and immunosuppressive therapy.     

Role of BK virus infection in end‐stage renal disease patients waiting for kidney transplantation – viral replication dynamics from pre‐ to post‐transplant

We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre‐ to post‐transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre‐transplantation, 12 h, and three and six months post‐transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication – considered a marker of infection – was 20% in pre‐transplant patients. All pre‐transplant‐positive patients remained positive post‐transplant, whereas the majority of pre‐transplant‐negative patients remained negative. Viremia dynamics classification revealed three clusters of patients: Cluster A++, pre‐transplant‐positive patients (20%) who tested positive at least once post‐transplant; Cluster B?+, pre‐transplant‐negative patients (28%) who tested positive at least once post‐transplant; and Cluster C– –, pre‐transplant‐negative patients (52%) who remained negative throughout. These clusters presented significant differences related to the prevalence of substantially positive patients with high plasma viral load (>10³ copies/mL) in cluster A, but not in donors’ or grafts’ characteristics. We suggest that pre‐transplant viral status should be considered as an additional risk factor for post‐transplant BKV replication. Therefore, pre‐transplant BKV infection screening in kidney transplant patients should be performed for improving planning of personalized immunosuppressant schemes and specific post‐transplant surveillance.     

Considerations in the medical management of pregnancy in transplant recipients

Pregnancy, although rare in the patient with end-stage renal disease, is not uncommon in the transplant recipient. Physicians taking care of transplant recipients must be able to inform patients about the potential risks of pregnancy in this setting. The patient and her partner must know that the risks associated with pregnancy increase with worsening kidney function and hypertension. Current consensus opinion is that pregnancy can be relatively safely undertaken by 1 year after transplant if the patient has had no rejections during the year, allograft function is adequate, there are no infections that could affect the fetus, the patient is not taking teratogenic medications, and immunosuppressive medication dosing is stable. Consideration must be given to immunosuppression during pregnancy both with respect to the specific agents as well as the level of dosing. None of the medications are FDA category A; all are B or higher. Part of planning for pregnancy should include an evaluation of immunosuppression medication and a plan to modify the regimen prior to conception if its use may be risky for the developing fetus. Rejection can occur during a kidney transplant, so maintaining adequate immunosuppression is important. Other issues that need to be managed when caring for a pregnant transplant patient include: potential for infection (urinary tract infections are very common), hypertension, and anemia. The type of delivery, posttransplant contraception, and breast-feeding also need to be addressed.     

Determining the effect of immunosuppressant adherence on graft failure risk among renal transplant recipients

The objective was to use the United States Renal Data System (USRDS) to quantify the relationship between immunosuppressant therapy (IST) adherence and risk of graft failure among adult renal transplant recipients (RTRs). A secondary objective was to examine the relationship among select patient characteristics and IST adherence. The study sample included adult RTRs who: received primary transplant between January 1, 1999 and December 31, 2005; experienced graft survival for at least 12 months post‐transplant and had at least 12 months of data in the USRDS; utilized Medicare coverage for IST; and were prescribed cyclosporine or tacrolimus. IST adherence was measured by medication possession ratio (MPR). Pearson chi‐square tests were used to examine associations between patient characteristics and MPR quartiles. Cox proportional hazards regression was used to assess relationships among time to graft failure, MPR, and patient characteristics. Thirty‐one thousand nine hundred and thirteen RTRs met inclusion criteria. Older age, female gender, white race, deceased donors, and tacrolimus were associated with greater adherence (p < 0.001). Cox proportional hazard modeling indicated greater adherence, white race, and having a living donor were significantly associated with longer graft survival (p < 0.05). Future prospective studies should further examine the clinical significance of IST nonadherence as it relates to graft failure.     

Higher mycophenolate dosage is associated with an increased risk of squamous cell carcinoma in kidney transplant recipients

BackgroundKidney transplant recipients are at increased risk of keratinocyte cancers, namely squamous cell and basal cell carcinomas (SCCs and BCCs). This is primarily due to the high levels of immunosuppression that are required to prevent allograft rejection. Different immunosuppressive medications confer different risks, and the effect of mycophenolate mofetil on SCC and BCC risk is unclear. We explored the relationship between mycophenolate dose prescribed over the entire transplant period and the risk of SCC and BCC.MethodsKidney transplant recipients from Queensland, Australia, were recruited between 2012 and 2014 and followed until mid-2016. During this time transplant recipients underwent regular skin examinations to diagnose incident SCCs and BCCs. Immunosuppressive medication regimens were obtained from hospital records, and the average mycophenolate dose/day over the entire transplantation period was calculated for each patient. Doses were divided into three ranked groups, and adjusted relative risks (RR_adj) of developing SCC and BCC tumours were calculated using negative binomial regression with the lowest dosage group as reference. Recipients who had used azathioprine previously were excluded; further sub-group analysis was performed for other immunosuppressant medications.ResultsThere were 134 kidney transplant recipients included in the study. The average age was 55, 31% were female and 69% were male. At the highest median mycophenolate dose of 1818 mg/day the SCC risk doubled (RR_adj 2.22, 95% CI 1.03–4.77) when compared to the reference group of 1038 mg/day. An increased risk persisted after accounting for ever-use of ciclosporin, ever-use of tacrolimus, and when excluding mammalian target of rapamycin users. This increased risk was mainly carried by kidney transplant recipients immunosuppressed for five or more years (RR_adj = 11.05 95% CI 2.50–48.81). In contrast, there was no significant association between BCC incidence and therapy with the highest compared with the lowest mycophenolate dosage (RR_adj = 1.27 95% CI 0.56–2.87).ConclusionHigher mycophenolate dosage is associated with increased SCCs in kidney transplant recipients, particularly those immunosuppressed for more than five years. The increased SCC risk persists after accounting for usage of other immunosuppressant medications.     

Evaluation of an immunosuppressant side effect instrument

BACKGROUND: Clinicians continue to be compelled to evaluate the impact of immunosuppressive medication side effects on the quality of life of transplant recipients. We Were asked to develop an instrument to measure side effects in immunosuppressed transplant recipients. OBJECTIVE: To construct an instrument that measures the impact and severity of side effects of immunosuppressive medications used in transplantation and to assess the reliability and validity of the newly developed instrument called the Memphis Survey. DESIGN: The instrument was constructed by a panel of physicians, nurses, and pharmacists with experience in treating transplant recipients. A small group of kidney transplant recipients (n= 13) provided pilot data for refining and testing the instrument. A national sample of kidney, liver, and heart transplant recipients (n = 505) provided data that were used to further develop the instrument. ANALYSIS: Factor analysis was used to determine the psychological dimensions underlying the instrument and to guide the construction of scales from the survey items. The instrument scales were then computed from the dataset of 505 transplant recipients to quantify the impact of immunosuppressant side effects on the quality of life of transplant recipients. RESULTS AND CONCLUSION: Analyses showed the final instrument scales to be valid and reliable. Exploratory analysis suggests the need for further testing of the instrument to determine gender differences.     

Associations of characteristics of renal transplant recipients with clinicians' perceptions of adherence to immunosuppressant therapy

BACKGROUND: The objective of the study was to determine surveillance criteria for renal transplant recipients (RTRs) at highest risk for immunosuppressant therapy nonadherence. METHODS: Retrospective analyses were performed on follow-up data in the United States Renal Data System. Those who received transplants between January 1, 1995 and December 31, 2002, had at least 36 months of follow-up data, and did not receive a second renal transplant were included in the analyses. The risk of nonadherence was estimated by random effects logistic regression while controlling for age, gender, race, education, donor type, primary insurance, time since transplant, and immunosuppressant medications using the STATA software (College Station, TX). Association between nonadherence and graft failure was also examined. RESULTS: A total of 53,997 individuals met the inclusion criteria. About 6% of RTRs were reported nonadherent. Nonadherence risk increased with time posttransplant and decreased with age (P<0.001). RTRs who were male, nonwhite, or used mycophenolate mofetil or tacrolimus were more likely to be nonadherent with odds ratios (OR) of 1.36, 1.99, 1.13, and 1.31, respectively (P<0.05) than RTRs who used cyclosporine, steroids, azathioprine, or had Medicare (P<0.05). Nonadherent RTRs were more likely to experienced graft failure (P<0.001). CONCLUSIONS: Interventions to improve adherence should target younger RTRs, male RTRs, nonwhite RTRs, and those not on Medicare to reduce risk of graft failure.