Prabhakar K. Baliga

Organ donation and utilization in the United States, 2004

This article discusses issues directly related to the organ donation process, including donor consent, donor medical suitability, non‐recovery of organs, organs recovered but not transplanted, expanded criteria donors (ECD), and donation after cardiac death (DCD). The findings and topics covered have important implications for how to evaluate and share best practices of organ donation as implemented by organ procurement organizations (OPOs) and major donor hospitals in the same donation service areas (DSAs). In 2002 and 2003, US hospitals referred more than one million deaths or imminent deaths to the OPOs of their DSA. Referrals increased by nearly 10% from 2002 to 2003 (1,022,280 to 1,121,392). Donor consents have increased by about 5% and the number of total deceased donors has risen from 6,187 to 6,455. Since multiple organs are recovered from most donors, this increase allowed more than 500 additional wait‐listed candidates to receive an organ transplant than in the prior year. Non‐traditional donor sources have experienced a large rate of increase; in 2003 the number of ECD kidney donors increased by 8% and the number of DCD donors increased by 43%, from 189 donors in year 2002 to 271 donors in 2003.

Organ donation and utilization in the United States, 1999-2008: Special feature

Despite the Organ Donation Breakthrough Collaboratives work to engage the transplant community and the suggested positive impact from these efforts, availability of transplanted organs over the past 5 years has declined. Living kidney, liver and lung donations declined from 2004 to 2008. Living liver donors in 2008 dropped to less than 50% of the peak (524) in 2001. There were more living donors that were older and who were unrelated to the recipient. Percentages of living donors from racial minorities remained unchanged over the past 5 years, but percentages of Hispanic/Latino and Asian donors increased, and African American donors decreased. The OPTN/UNOS Living Donor Transplant Committee restructured to enfranchise organ donors and recipients, and to seek their perspectives on living donor transplantation. In 2008, for the first time in OPTN history, deceased donor organs decreased compared to the prior year. Except for lung donors, deceased organ donation fell from 2007 to 2008. Donation after cardiac death (DCD) has accounted for a nearly 10‐fold increase in kidney donors from 1999 to 2008. Use of livers from DCD donors declined in 2008 to 2005 levels. Understanding health risks associated with the transplantation of organs from ‘high‐risk’ donors has received increased scrutiny.

CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity.

T cell activation is the result of antigen-specific interactions with the TCR/CD3 complex and costimulation via other T cell surface receptors. Prevention of costimulation can result in clonal anergy. CTLA4Ig is a fusion protein that binds with high-affinity to the B7/BB1 ligand and blocks the interaction of this ligand with CD28 and CTLA4. We explored the immunosuppressive effects of CTLA4Ig in a murine nonvascularized heterotopic cardiac transplant model and in a model of cell mediated immunity. CTLA4Ig administered in vivo for two days at the time of transplantation resulted in significant prolongation of allograft survival (55 +/- 2.0 vs. 12.2 +/- 0.5 days for control, P < 0.03). Administration at later times or to previously primed animals produced no prolongation of graft survival. CTLA4Ig administered during in vivo immunization to the hapten TNP suppressed the contact sensitivity response and inhibited the subsequent in vitro generation of secondary TNP-specific CTL. CTLA4Ig administered in vivo had no effect on subsequent primary alloantigen-specific CTL or MLR responses--however, when added to culture the fusion protein inhibited the MLR response by 80%, but not the alloantigen-specific CTL response. CTLA4Ig inhibited CD4+ and CD8+ proliferative and cytokine responses to alloantigen. Flow cytometry showed no changes in distribution of subpopulations of T cells. These results confirm the immunosuppressive activity of CTLA4Ig in vivo in an allograft model and show that both CD4+ and CD8+ T cells are suppressed by CTLA4Ig. The most efficacious time of administration is during priming of the immune response at the time of antigen presentation.

A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C

This randomized, prospective, multicenter trial compared the safety and efficacy of steroid‐free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA–positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid‐free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid‐free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS. Liver Transpl, 2011.

Consensus conference on best practices in live kidney donation: Recommendations to optimize education, access, and care

Live donor kidney transplantation is the best treatment option for most patients with late‐stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5–6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

Mobile Health Medication Adherence and Blood Pressure Control in Renal Transplant Recipients: A Proof-of-Concept Randomized Controlled Trial

Background Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities (eg, hypertension, diabetes). These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients’ physiological data. This technology is also relatively inexpensive, has an intuitive interface, and provides the capability for real-time personalized feedback to help motivate patient self-efficacy. Automated summary reports of patients’ adherence and blood pressure can easily be uploaded to providers’ networks helping reduce clinical inertia by reducing regimen alteration time. Objective The aim of this study was to assess the feasibility, acceptability, and preliminary outcomes of a prototype mobile health (mHealth) medication and blood pressure (BP) self-management system for kidney transplant patients with uncontrolled hypertension. Methods A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design. The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback. A 3-month proof-of-concept randomized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray. Participants randomized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging. Controls received standard of care and their adherence continued to be monitored with the medication tray reminders turned off. Providers received weekly summary reports of patient medication adherence and BP readings. Results Participation and retention rates were 41/55 (75%) and 31/34 (91%), respectively. The prototype system appears to be safe, highly acceptable, and useful to patients and providers. Compared to the standard care control group (SC), the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations. Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the standard care group (7 adjustments in 5 patients versus 3 adjustments in 3 patients) during the 3-month trial based on the information provided in the weekly reports. Conclusions These data support the acceptability and feasibility of the prototype mHealth system. Further trials with larger sample sizes and additional biomarkers (eg, whole blood medication levels) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control after kidney transplantation over longer time periods. Trial Registration Clinicaltrials.gov NCT01859273; http://clinicaltrials.gov/ct2/show/NCT01859273 (Archived by WebCite at http://www.webcitation.org/6IqfCa3A3).

Posttransplant survival in pediatric fulminant hepatic failure: The SPLIT experience

Pediatric patients with fulminant hepatic failure (FHF) tend to be the sickest and have the most urgent need for a liver transplant. The purpose of this analysis was to identify factors associated with posttransplant survival in this subset of patients. Data on all FHF patients registered in the Studies of Pediatric Liver Transplantation (SPLIT) registry from 1995 to 2002 were analyzed. Demographics such as age, gender, race, weight, and etiology of liver disease were recorded. Pretransplant degree of encephalopathy; intubation; dialysis; laboratory parameters such as serum bilirubin and international normalized ratio of coagulopathy (INR); and type of graft: cadaveric whole, cadaveric technical variant, or living donor were analyzed to determine effects on patient survival. Overall, FHF accounted for 12.9% (141 / 1,092) of primary transplants performed between 1995 and 2002. The etiology of liver disease was unknown in the vast majority of children (126 / 141; 89.4%). Mortality while on the waiting list for FHF children is significantly higher than for children with other liver disease (P < .0001). Six‐month survival posttransplant for patients with FHF (74.5%) is significantly lower (P < .0001) than those with chronic liver disease (88.9%). A multivariate model demonstrates that the highest risk group includes those children with grade 4 encephalopathy (P < .0001), infants less than 1 year of age (P = .018), and children requiring dialysis prior to transplantation (P = .002). Pretransplant bilirubin and INR were not significant predictors of posttransplant survival after controlling for the other significant factors. Living donor and split / reduced grafts did not have a significantly increased risk of posttransplant death compared to whole grafts. In conclusion, despite advances in the surgical techniques and changes in organ allocation, pediatric patients with FHF continue to have a high pretransplant mortality and less successful posttransplant survival compared to children with chronic liver disease. (Liver Transpl 2004;10:1364–1371.)

Patient Attitudes Toward Mobile Phone-Based Health Monitoring: Questionnaire Study Among Kidney Transplant Recipients

Background Mobile phone based remote monitoring of medication adherence and physiological parameters has the potential of improving long-term graft outcomes in the recipients of kidney transplants. This technology is promising as it is relatively inexpensive, can include intuitive software and may offer the ability to conduct close patient monitoring in a non-intrusive manner. This includes the optimal management of comorbidities such as hypertension and diabetes. There is, however, a lack of data assessing the attitudes of renal transplant recipients toward this technology, especially among ethnic minorities. Objective To assess the attitudes of renal transplant recipients toward mobile phone based remote monitoring and management of their medical regimen; and to identify demographic or clinical characteristics that impact on this attitude. Methods After a 10 minute demonstration of a prototype mobile phone based monitoring system, a 10 item questionnaire regarding attitude toward remote monitoring and the technology was administered to the participants, along with the 10 item Perceived Stress Scale and the 7 item Morisky Medication Adherence Scale. Results Between February and April 2012, a total of 99 renal transplant recipients were identified and agreed to participate in the survey. The results of the survey indicate that while 90% (87/97) of respondents own a mobile phone, only 7% (7/98) had any prior knowledge of mobile phone based remote monitoring. Despite this, the majority of respondents, 79% (78/99), reported a positive attitude toward the use of a prototype system if it came at no cost to themselves. Blacks were more likely than whites to own smartphones (43.1%, 28/65 vs 20.6%, 7/34; P=.03) and held a more positive attitude toward free use of the prototype system than whites (4.25±0.88 vs 3.76±1.07; P=.02). Conclusions The data demonstrates that kidney transplant recipients have a positive overall attitude toward mobile phone based health technology (mHealth). Additionally, the data demonstrates that most kidney transplant recipients own and are comfortable using mobile phones and that many of these patients already own and use smart mobile phones. The respondents felt that mHealth offers an opportunity for improved self-efficacy and improved provider driven medical management. Respondents were comfortable with the idea of being monitored using mobile technology and are confident that their privacy can be protected. The small subset of kidney transplant recipients who are less interested in mHealth may be less technologically adept as reflected by their lower mobile phone ownership rates. As a whole, kidney transplant recipients are receptive to the technology and believe in its utility.

Racial disparities in living kidney donation : Is there a lack of willing donors or an excess of medically unsuitable candidates?

Background. Live kidney donation is safe for healthy donors and an effective treatment for patients with end-stage renal disease. Many potential donors are referred for live kidney donation, but only a small percentage donate. This study aims to determine reasons for nondonation and establish if racial differences exist. Methods. A retrospective database and chart review of all patients that were referred for potential live kidney donation from January 1, 2000 to December 31, 2004 was conducted. Results. In all, 30.3% of referred potential live kidney donors were lost to follow-up. Primary reasons for nondonation (n=1,050) included unsuitable donor health (43.1%) and recipient-based causes (41.3%). Immunologic incompatibility accounted for 9.7% of all nondonations. Racial differences indicated more African Americans had incompatible blood types (P=0.01) or ineligible recipients (26.7% vs. 14.4%, P<0.01). More non-African Americans donated (13.2% vs. 4.6%, P<0.01) or were halted because the potential recipient received another organ (living/cadaveric) (20.0% versus 7.9%), P<0.01). Nondonation due to overall donor health (including diabetes and hypertension) did not differ between races, but subanalysis indicated more African American nondonation was due to high body mass index (P=0.01). Conclusions. Determining the reason behind nondonation is a first step towards understanding low rates of live kidney donation. More African American donor referrals are lost to follow-up while rates of other reasons were similar among races. This may indicate that African Americans are not more frequently medically unsuitable, but that the divergence in rates of live kidney donation is caused by a disparity in willingness to donate among African Americans.

Racial disparities in organ donation and why.

Purpose of reviewHigh prevalence of comorbidities such as diabetes, hypertension, obesity, hepatitis B and C, in minority groups, results in racial minorities being disproportionally represented on transplant waiting lists. Organ transplantation positively impacts patient survival but greater access is limited by a severe donor shortage. Recent findingsUnfortunately, minority groups also suffer from disparities in deceased and living donation. African-Americans comprise 12.9% of the population and 34% of the kidney transplant waiting list but only 13.8% of deceased donors. Barriers to minority deceased donation include: decreased awareness of transplantation, religious or cultural distrust of the medical community, fear of medical abandonment and fear of racism. Furthermore, African-Americans comprise only 11.8% of living donors. Barriers to minority living donation include: unwillingness to donate, medical comorbid conditions, trust or fear of medical community, loss to follow-up, poor coping mechanisms, financial concerns, reluctance to ask family members and friends, fear of surgery, and lack of awareness about living donor kidney transplantation. SummaryTransplant center-based education classes significantly and positively impact African-American concerns and beliefs surrounding living donation. Community and national strategies utilizing culturally sensitive communication and interventions can ameliorate disparities and improve access to transplantation.