Early surveillance biopsy utilization and management of pediatric renal allograft acute T cell-mediated rejection in Canadian centers: Observations from the PROBE multicenter cohort study.

BACKGROUND: Early TCMR surveillance with protocol kidney biopsy is used differentially among pediatric kidney transplant centers. Little has been reported about actual center-based differences, and this variability may influence TCMR ascertainment, treatment, and monitoring more broadly. METHODS: Data from the PROBE multicenter study were used to identify patients from centers conducting ESB or LSIB. ESB was defined as >50% of patients having at least 1 surveillance biopsy in the first 9 months. Patients were compared for number of biopsies, rejection episodes, treatment, and follow-up monitoring. RESULTS: A total of 261 biopsies were performed on 97 patients over 1-2 years of follow-up. A total of 228 (87%) of biopsies were performed in ESB centers. Compared to LSIB centers, ESB centers had 7-fold more episodes of TCMR diagnosed on any biopsy [0.8 ± 1.2 vs 0.1 ± 0.4; P < .001] and a 3-fold higher rate from indication biopsies [0.3 ± 0.9 vs 0.1 ± 0.3; P = .04]. The proportion of rejection treatment varied based on severity: Banff borderline i1t1 (40%);>i1t1 and < Banff 1A (86%); and ≥ Banff 1A (100%). Biopsies for follow-up were performed after treatment in 80% of cases (n = 28) of rejection almost exclusively at ESB centers, with 17 (61%) showing persistence of TCMR (≥i1t1). CONCLUSIONS: Practice variation exists across Canadian pediatric renal transplant centers with ESB centers identifying more episodes of rejection. Additionally, treatment of Banff borderline is not universal and varies with severity regardless of center type. Lastly, follow-up biopsies are performed inconsistently and invariably show persistence of rejection.

Variation in immunosuppression practices among pediatric liver transplant centers-Society of Pediatric Liver Transplantation survey results.

BACKGROUND: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. METHODS: A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. RESULTS: Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. CONCLUSION: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.

Case Report: Early Transplant Rejection of a Methanol-Intoxicated Donor Heart in a Young Female Patient. A Diagnostic Approach With CMR, Cardiac Biopsy, and Genetic Risk Assessment.

This case report describes the contributions of multimodality imaging, cardiac biopsy, and genetic sequencing to the diagnosis and management of heart transplant rejection in a 23-year old patient with dilated cardiomyopathy.

Lung Transplantation.

Lung transplantation is an appropriate therapeutic option for select patients with end-stage lung diseases and offers the possibility of improved quality of life and longer survival. Unfortunately, the transplant recipient is at risk for numerous immunologic, infectious, and medical complications that threaten both of these goals. Median survival after lung transplantation is approximately 6 years. Optimizing outcomes requires close partnership between the patient, transplant center, and primary medical team. Early referral to a transplant center should be considered for patients with idiopathic pulmonary fibrosis and related interstitial lung diseases due to risk of acute exacerbation and accelerated development of respiratory failure.

Socioeconomic Status and Kidney Transplant Outcomes in a Universal Healthcare System: A Population-based Cohort Study.

BACKGROUND: Conflicting evidence exists regarding the relationship between socioeconomic status (SES) and outcomes after kidney transplantation. METHODS: We conducted a population-based cohort study in a publicly funded healthcare system using linked administrative healthcare databases from Ontario, Canada to assess the relationship between SES and total graft failure (ie, return to chronic dialysis, preemptive retransplantation, or death) in individuals who received their first kidney transplant between 2004 and 2014. Secondary outcomes included death-censored graft failure, death with a functioning graft, all-cause mortality, and all-cause hospitalization (post hoc outcome). RESULTS: Four thousand four hundred-fourteen kidney transplant recipients were included (median age, 53 years; 36.5% female), and the median (25th, 75th percentile) follow-up was 4.3 (2.1-7.1) years. In an unadjusted Cox proportional hazards model, each CAD $10000 increase in neighborhood median income was associated with an 8% decline in the rate of total graft failure (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.97). After adjusting for recipient, donor, and transplant characteristics, SES was not significantly associated with total or death-censored graft failure. However, each CAD $10000 increase in neighborhood median income remained associated with a decline in the rate of death with a functioning graft (adjusted (a)HR, 0.91; 95% CI, 0.83-0.98), all-cause mortality (aHR, 0.92; 95% CI, 0.86-0.99), and all-cause hospitalization (aHR, 0.95; 95% CI, 0.92-0.98). CONCLUSIONS: In conclusion, in a universal healthcare system, SES may not adversely influence graft health, but SES gradients may negatively impact other kidney transplant outcomes and could be used to identify patients at increased risk of death or hospitalization.

Cost Implications of New National Allocation Policy for Deceased Donor Kidneys in the United States.

BACKGROUND: In December 2014, a new national deceased donor kidney allocation policy was implemented, which allocates kidneys in the top 20% of the kidney donor profile index to candidates in the top 20% of expected survival. We examined the cost implications of this policy change. METHODS: A Markov model was applied to estimate differences in total lifetime cost of care and quality-adjusted life years (QALY). RESULTS: Under the old allocation policy, average lifetime outcomes per listed patient discounted to 2012 US dollars were US $342,799 and 5.42 QALY, yielding US $63,775 per QALY gained. Under the new policy, average lifetime cost was reduced by US $2090 and lifetime QALYs increased by 0.03. Thus, the new policy improved on the old policy by producing more QALYs at lower cost. The present value of total lifetime cost savings from the policy change is estimated to be US $271 million in the first year and US $55 million in subsequent years. The higher transplant rates and allograft survival expected for candidates in the top 20% of expected survival would decrease costs by reducing time on dialysis. Most cost savings are expected to accrue to Medicare, and most increased access to transplant is expected in private payer populations. CONCLUSIONS: The new allocation policy was found to be dominant over the old policy because it increases QALYs at lower cost.

Fibrin Glue Injections: A Minimally Invasive and Cost-Effective Treatment for Post-Renal Transplant Lymphoceles and Lymph Fistulas.

Pelvic lymphoceles/lymph fistulas are commonly observed after kidney allotransplantation, especially when the kidney is placed in a retroperitoneal position. While the majority are <5 cm in diameter and resolve without intervention, some may continue to enlarge, and cause local or systemic symptoms or graft dysfunction. Among 1662 recipients of both living and deceased donor kidney transplants between January 2003 and July 2014, we found 46 (2.7%) patients with symptomatic lymphoceles requiring intervention. We studied the clinical outcomes and charges for three treatment modalities including open surgical drainage (22), laparoscopic surgical drainage (11), and percutaneous fibrin glue injections into the drained lymphocele cavity (13). The patient demographics and clinical characteristics were comparable for each treatment group, although maintenance immunosuppressive drugs differed by era. We found fibrin glue injections resulted in significantly lower (p = 0.04) rates of recurrence (1; 7.7%) than either laparoscopic (6; 54%) or open surgical drainage (6; 27.3%). In addition, fibrin glue injections generated significantly (p < 0.001) lower median ($4559) charges compared to either laparoscopic ($26,330) or open surgical drainage ($23,758). Fibrin glue treatment has the advantage of being an outpatient procedure, performed with the patient under local anesthesia, and does not incur the expense of an operative procedure or hospital admission associated with laparoscopic or open surgery.

Successes and lessons learned after more than a decade of upper extremity and face transplantation.

PURPOSE OF REVIEW: This review aims to present the most recent updates on face and upper-extremity allotransplantation. RECENT FINDINGS: To date, 27 face and more than 89 upper-extremity allotransplantations have been performed. Both the face and hand transplants restored form, function and patients' social integration. The complications were comparable with solid organs; however, face transplantation, as well as the combination of face and double hand transplantation, presented with significant morbidity and mortality. Evidence of chronic rejection was confirmed in hand transplants, but it has not been reported yet for facial transplantation. Novel immunosuppressive protocols have allowed a decrease in the number and dosages of traditional immunosuppressants. With increased awareness that following face and hand transplantation, the return of function is more important than anatomical restoration of the missing parts, there has been an important shift in the ethical debate weighing the risks and benefits of face and hand allotransplantation. SUMMARY: Early results after face and upper extremity transplantation are promising, with 5-year survival rates greater than in solid organ transplants. However, these procedures still need to be closely monitored and the outcome data should be rigorously reported to the central patient registry database to allow continuous surveillance.

Late acute liver allograft rejection; a study of its natural history and graft survival in the current era.

BACKGROUND: Late acute rejection (LAR) after liver transplantation is often associated with poor clinical outcomes. We reviewed our experience of managing LAR in the current era to determine its natural history. METHODS: A database of 970 consecutive adult liver transplants was reviewed retrospectively. LAR was defined as histologically proven acute cellular rejection occurring more than 90 days after transplantation. RESULTS: The incidence of LAR was 11%, with a mean time of 565 days (median, 311 days; range, 90-2922 days) after transplantation. The highest rates for LAR were in seronegative hepatitis (17%), primary biliary cirrhosis (16%), and primary sclerosing cholangitis (13%) with an odds ratio of 2.3, 2.1, and 1.8, respectively. Logistic regression showed that younger recipients, primary biliary cirrhosis, and previous graft loss were independent predictors of LAR (P<0.001). Mean trough whole blood tacrolimus levels were at their lowest levels 1 week before the diagnosis of rejection (5.5 ng/mL; SD, 2.6) compared with levels of 7.7 ng/mL 4 weeks before rejection, showing a clear temporal relation. Graft survival was worse in those with LAR (P<0.01), whereas the best graft survival was among early acute rejection cases (85% 10-year survival; P<0.01). Poor response to treatment correlated with the development of ductopenic rejection (r=0.3; P<0.01). Approximately half with early ductopenic rejection eventually died (n=15). CONCLUSION: LAR continues to provide a risk to patient and graft survival: understanding risk factors may allow an improvement in monitoring and early intervention and so prevent early graft loss.

Hematopoietic cell transplantation for thalassemia: a global perspective BMT tandem meeting 2013.

Hematopoietic cell transplantation (HCT) remains the sole available curative option for patients with ß-thalassemia major. Expanded and improved supportive therapies for thalassemia now routinely extend the life span of affected individuals well into adulthood. Consequently, in regions of the world where this care is readily available, HCT has been pursued infrequently, in part owing to concerns about an expected lack of balance between risks and benefits. More recently, however, recognition of significant health problems in older patients with thalassemia, along with recognition of increased risks of graft-versus-host disease (GVHD), graft rejection, and impaired organ function leading to inferior HCT outcomes in this particular group, seem to be turning the wheels and tipping the balance again in the direction of consideration for earlier HCTs. In contrast, in countries where thalassemia is most prevalent (>100,000 new children born each year in Middle East and southeast Asia), lack of supportive care standards together with often insufficient access to dedicated health care facilities, results in the majority of these children not reaching adulthood, further supporting the need for expanded access to HCT for these patients. The cost of HCT is equivalent to that of a few years of noncurative supportive care, such that HCT in low-risk young children with a compatible sibling is justified not only medically and ethically but also financially. International cooperation can play a major role in increasing access to safe and affordable HCT in countries where there is a considerable shortage of transplantation centers. In this article, we review the current status of bone marrow transplantation for thalassemia major, with particular emphasis on a global prospective.

Monitoring and managing graft health in the kidney transplant recipient.

Ongoing monitoring of kidney transplants is a widely accepted and practiced part of posttransplantation management. One reason to monitor is to evaluate whether the transplant is stable. The transplant community evaluates stability by checking kidney function. Despite problems with sensitivity and specificity, obtaining serial serum creatinine levels is the most common approach to assessing kidney function. Some programs supplement serial serum creatinine levels with surveillance kidney biopsies. Although not uniformly accepted as beneficial, surveillance biopsies are useful in select subsets of patients such as highly sensitized recipients. Recent biopsy studies shed light on which histopathology findings portend poor prognoses. The Long-Term Deterioration of Kidney Allograft Function Study (DeKAF) and similar studies that will prospectively evaluate therapeutic interventions should help the transplant community better define how to monitor and manage the kidney transplant optimally. In the meantime, Kidney Diseases: Improving Global Outcomes (KDIGO) provides an evidence-based approach toward monitoring and managing the kidney transplant.

Solid-organ transplantation in childhood: transitioning to adult health care.

Pediatric solid-organ transplantation is an increasingly successful treatment for solid-organ failure. With dramatic improvements in patient survival rates over the last several decades, there has been a corresponding emergence of complications attributable to pretransplant factors, transplantation itself, and the management of transplantation with effective immunosuppression. The predominant solid-organ transplantation sequelae are medical and psychosocial. These sequelae have a substantial effect on transition to adult care; as such, hurdles to successful transition of care arise from the patients, their families, and pediatric and adult health care providers. Crucial to successful transitioning is the ongoing development of a sense of autonomy and responsibility for one's own care. In this article we address the barriers to transitioning that occur with long-term survival in pediatric solid-organ transplantation. Although a particular transitioning model is not promoted, practical tools and strategies that contribute to successful transitioning of pediatric patients who have received a transplant are suggested.

Causes of re-hospitalization in different post kidney transplantation periods.

BACKGROUND: Post kidney transplantation Re-admissions are focused because they are costly and cause morbidity, or may end with unsatisfactory endpoints namely graft loss or death. We compared the pattern, outcome and cost of re-admissions in different post-kidney transplantation periods. MATERIAL/METHODS: In a retrospective study, 562 consecutive re-admissions of kidney recipients categorized to early (during first 6 months; n=278); intermediate (6-24 months; n=115); and late (24 months and afterwards, n=169) hospitalizations. Primary outcome measures included hospitalization pattern (cause and length of hospital stay), and secondary outcome measure were assessed (mortality and graft loss during hospitalization) and costs. RESULTS: The causes of rehospitalization were surgical complication (84 percent), infection (51 percent), graft rejection (45 percent), and malignancy (0.6 percent), in early phase, graft rejection (44 percent), infection (42 percent), surgical complication (13 percent), and malignancy (5 percent), in intermediate phase, and graft rejection (45 percent), infection (39 percent), surgical complication (3 percent), and malignancy (0.06 percent), in late phase. So, infections and surgical complications showed a decreasing trend from early to late post transplant phase, while malignancies showed a peak in intermediate phase. The length of hospital stay (12+/-11, 10+/-10, 9+/-7, p=0.001) and hospitalization charges (708+/-36, 468+/-333, 413+/-262 united states Dollars, p=0.035) were significantly higher in the early post transplant phase. Mortality (p=0.755) and graft loss during hospitalization (p=0.246) remained the same in all time intervals. CONCLUSIONS: Early post-kidney transplantation phase, with a higher risk of infections and surgical complications, health care system experience longer and more costly hospitalizations.

KDIGO clinical practice guideline for the care of kidney transplant recipients.

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression, graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially on the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.

Postlung transplant rehospitalization: a study of causes, health care burden, and outcomes.

OBJECTIVES: Rehospitalization is a significant burden for transplant systems, which use data on hospitalization to monitor practice outcomes. In this study, all rehospitalizations after successful lung transplant performed in our medical center during an 8-year period were assessed for cause, health care resource use, cost, and outcome. MATERIALS AND METHODS: We performed a retrospective chart review of all rehospitalizations of lung transplant recipients in Masih Daneshvari Hospital in Darabad, Tehran, between 2000 and 2008. Baseline data (each patient's age at transplant and rehospitalization, sex, primary lung disease, medications used), cause of rehospitalization (infection, graft rejection, surgical complications, type of infection), health care resources use (length of hospital stay, intensive care unit stay, physician visits, imaging), rehospitalization costs (accommodations, personnel, drugs, paraclinical [ie, laboratory] tests, supplies, procedures) and outcome (death, survival) were noted. RESULTS: In 69% of patients who were rehospitalized after having received a lung transplant, the cause was infection. Other causes were acute rejection in 31% and surgical complications in 6.9%. In 10.3% of those patients, the primary cause for rehospitalization could not be specified. The mean (SD) duration of rehospitalization was 12.8 -/+ 10.4 days. Treatment in the intensive care unit was necessary for 93.1% of the study subjects. The mean (SD) number of physician visits was 27.8 -/+ 27.7, and the fatality rate in the patients studied was 13.8%. CONCLUSIONS: These data may guide the monitoring of the causes, burden, and outcomes of lung transplants performed in our medical center in Iran and in other medical centers.

Restarting the clock...again: ethical considerations in retransplantation.

Cardiac and pulmonary transplantation has revolutionized end-stage heart and lung therapy. With the advent of cyclosporine and other immunosuppressive therapies, many patients lead productive lives. Unfortunately, other patients who have undergone cardiac and/or pulmonary transplantation do not have favorable results. In fact, some require retransplantation to live. Because of organ scarcity, healthcare professionals and patients must examine not only retransplantation survival rates but also the ethical considerations when dealing with resource-limited organs. Given that retransplantation survival rates are not as favorable as those for primary transplantation and that no studies involving quality of life and morbidity could be located, considerable thought should be given to this controversial practice.

Lung transplantation at Duke University.

Clinical lung transplantation continues to grow worldwide. Advances in donor selection and management have been critical to support the expanded growth of lung transplant as a therapeutic option for patients with advanced lung disease. In recent years, allocation in the US has changed to a disease severity based system that has led to a dramatic reduction of deaths on the waiting list with concomitant increases in transplantation of recipients who are now sicker, older, and more likely to have interstitial lung disease. Increased experience with the LAS will help to further refine optimal recipient selection and balance urgency with utility. Our center's experience demonstrates survival is comparable post-LAS as compared to pre-LAS despite transplantation of increasingly ill recipients. After transplantation, the incidence of severe PGD has decreased in recent years with advances in donor lung management and perseveration. In cases of severe PGD, VV ECMO has provided our center with a successful method of supporting patients and reducing mortality immediately following transplantation. Long-term outcomes after lung transplantation continue to be limited by BOS, a condition of progressive allograft dysfunction. Our center has led research that identified gastric reflux as a potential contributing factor to posttransplant allograft dysfunction and suggested that Nissen fundoplication surgery might help prevent the development of BOS. Continued refinements in donor management and selection, prevention and treatment of PGD, and enhanced understanding of the mechanisms of BOS will support further growth of lung transplantation and further improvements in overall posttransplant outcomes.

Renal transplantation today.

BACKGROUND: The first successful renal transplant was carried out more than five decades ago between identical twins. At these early days, acute rejection was the limiting factor. DISCUSSION: Due to tremendous progress in immunosuppressive therapy and surgical technique, today, renal transplantation is the gold standard therapy for patients with end-stage renal disease. In fact, in comparison with chronic hemodialysis, renal transplantation offers an increase in quality of life while reducing comorbidities associated with dialysis treatment. RESULTS: Despite numerous beneficial achievements, no further improvement regarding patient outcome can be observed over the last two decades. Graft survival rates remain unchanged. The leading causes for graft loss are chronic allograft nephropathy and death with functioning graft. This might be related to a constant increase of the proportion of donors presenting extended donor criteria as well as a more liberal acceptance of candidates for a renal transplant. CONCLUSION: In the near future, one has to focus more closely on the posttransplant patient care to minimize factors associated with chronic allograft damage. These include post-transplant diabetes, hyperlipidemia, high blood pressure, cytomegalovirus infection, etc.

Identification of medication non-adherence factors in adolescent transplant patients: the patient's viewpoint.

Studies report a clear association between medication non-adherence and an unfavorable transplant outcome. The adolescent population, in particular, has difficulty adhering to post-transplant medication regimens. The purpose of this study is to identify, categorize and understand the opinions of adolescent transplant patients regarding why they may not take their medications as prescribed. From January to August 2005, nine adolescent kidney transplant patients at an urban medical center were surveyed and asked to rank-order 33 statements regarding their opinions on why adolescents may not take their medications as prescribed. Q-methodology, a powerful tool in subjective study, was used to identify and categorize the viewpoints of adolescents on this subject. Three factors emerged and were labeled to reflect their distinct viewpoints: (1) Medication Issues (e.g. taste, size, frequency, schedule), (2) Troubled Adolescent (e.g. poor home life, depression, overwhelming situation), and (3) Deliberate Non-Adherer (e.g. attention-seeker, infallible attitude). By understanding these different viewpoints and the factors that contribute to them, it may be easier to identify which management approach to non-adherence works best in specific subgroups of patients.