I. SPECIFIC AIMS
1. Prospectively assess primary and secondary outcomes of living kidney donation.
Primary outcomes of interest include surgical, medical, functional, and psychological outcomes. Our primary hypothesis is that, while living donors may experience short-term functional limitations, they are not at any increased risk of medical morbidity, functional impairment, or psychological complications at the final study endpoint (2 yrs). Secondary outcomes include donation costs (direct, indirect), satisfaction, decision stability, and miscellaneous consequences (e.g., problems getting and/or maintaining health or life insurance). Our secondary hypothesis is that living donors incur moderate non-reimbursed costs, but report very high levels of satisfaction and decision stability over time.
2. Identify the donor, recipient, and center variables that are most strongly associated with living donor outcomes at the 2-year follow-up assessment.
On the basis of previous literature, we will examine variables hypothesized or shown to be predictive of key donor outcomes, including sociodemographic characteristics, donor-recipient relationship type, obesity, smoking history, isolated medical complexities, mental health history, donation knowledge, dispositional optimism, and recipient characteristics (e.g., graft function, QOL). In addition, an important question in transplantation is the impact of provider/facility-level characteristics on outcomes and whether these differences exacerbate disparities in outcomes in certain patient populations. In this aim, we are evaluating whether the primary outcomes vary significantly between the seven centers based on several characteristics, including live donor kidney transplantation (LDKT) volume, ratio of LDKT to deceased donor transplants, pre-emptive LDKT volume, donor travel distance, and number of competing transplant centers within 100 miles, among other characteristics of the donor populations.
3. Identify disparities in donor outcomes and factors that are associated with such disparities.There are several potential disparities in living donor outcomes that have not yet been systematically examined. First, certain minorities have higher incidence of health conditions that can lead to kidney disease (e.g., hypertension, obesity, diabetes). The expansion of living donor eligibility criteria to include donors with well-controlled hypertension, obesity, or metabolic syndrome may place certain groups of individuals at higher risk for long-term negative outcomes following living kidney donation. Second, women historically represent the majority of living donors and we know little about gender disparities in donor outcomes. Third, there is some evidence that older living donors may be at higher risk of poorer outcomes, but this also warrants further examination. Finally, the relative impact of donation on those of lower socioeconomic status is largely unknown. It is possible that those with higher indirect donation expenses and/or without health insurance may have disparate outcomes relative to those with more financial resources and health insurance. We are evaluating whether disparities exist along these parameters and, if so, the factors associated with them.
II. RESEARCH DESIGN AND METHODS
A. Design OverviewThis is a seven center, prospective observational cohort study. A total of 280 living kidney donors, 280 LDKT recipients, and 160 healthy comparison subjects meeting all eligibility criteria are being enrolled. Participants complete the assessment protocol at 5 time points: prior to surgery (Baseline, T1), 1 month after surgery (T2), 6 months after surgery (T3), 12 months after surgery (T4), and 24 months after surgery (T5). The rationale for selecting these time points is that they correspond to the assessment intervals currently required by the Organ Procurement and Transplantation Network (United Network for Organ Sharing).
B. Study ParticipantsA total of 280 living kidney donors, 280 LDKT recipients, and 160 healthy comparison subjects meeting all eligibility criteria will be enrolled. We are enrolling both English and Spanish speaking participants into the study. The primary focus of the study is on assessing donor outcomes. The rationale for including the recipient is to examine the role that recipient factors play in predicting donor outcomes. There is preliminary evidence that some aspects of the recipient’s functioning (e.g., graft survival, QOL) are associated with certain functional and psychological outcomes in living donors. The inclusion of transplant recipients in the study permits further examination of this association over time and allows us to include other recipient variables that heretofore have been neglected (e.g., perceptions of the donor-recipient relationship). Also, we are recruiting a healthy, non-donor comparison group. A healthy comparison group allows us to address the question, “What if I had not donated my kidney?” These will be adults who completed one or more parts of the donor evaluation, but who did not proceed further for various non-medical reasons.Importantly, we are recruiting living donors into the study regardless of their recipient’s participation status. Even in the absence of the recipient’s participation, we will obtain valuable data about donor outcomes. However, because this is first-and-foremost a study evaluating donor outcomes, if a donor does not consent to participate in the study, we will not approach their recipient about study participation.Non-directed donors are being recruited into the study. If it is an anonymous donation, their recipient is not being approached about the study. In this case, only the donor is enrolled. If the non-directed donor has established a relationship (albeit a new one) with the intended recipient, then we attempt to enroll both the donor and the recipient into the study, just like any other donor-recipient pair.Donors participating in a kidney paired donation program (KPD) are being recruited into the study. In this instance, we enroll KPD donors and their intended recipient (i.e., the recipient with whom they are incompatible, not the recipient of their specific kidney).For each transplant recipient enrolled in the study, we determine if s/he had other potential donors who were initially screened or evaluated but who did not progress to donation surgery. This initial screening or evaluation may include an initial health history, ABO testing, and/or other preliminary tests. To qualify as a control subject, the non-donor may or may not have completed the entire evaluation, but none of the studies performed will have excluded them from donation. If an enrolled donor has more than one potential healthy control subject, we attempt to recruit them all into the study.
C. Inclusion and Exclusion CriteriaInclusion criteria:• ≥ 18 years old• residential or cell phone service• written informed consent• medically cleared for donor nephrectomy (donor)• medically cleared for transplant surgery (recipient)• did not progress to donation, although medically eligible (control)• completed preliminary labs (control)Exclusion criteria:• inability or unwillingness to provide informed consent• inability to speak and read English or Spanish
D. Primary and Secondary OutcomesPrimary Outcomes:Surgical: surgical complications, re-operation, length of hospital stay, wound pain intensity, surgical scarring, hospital re-admissionsMedical: blood pressure, creatinine, proteinuria, hematuria, diabetes, anemia, hyperlipidemia, body mass indexFunctional: quality of life, fatigue, physical activity, return to work/schoolPsychological: pressure/coercion, mood, body image, perceived donation benefits and consequences, life satisfaction, fear of kidney failure, donor-recipient relationship satisfactionSecondary Outcomes:
Direct costs, indirect costs, overall satisfaction, decision stability, unanticipated outcomes, inconvenience
E. Schedule of Assessments and ProceduresParticipants complete the assessment protocol at 5 time points: prior to surgery (Baseline, T1), 1 month after surgery (T2), 6 months after surgery (T3), 12 months after surgery (T4), and 24 months after surgery (T5). The exception to this schedule is that wound pain intensity data is collected at a more frequent interval during the first 8 post-donation weeks. Data from study participants are collected via medical record review, face-to-face visits, data acquired from their PCPs, telephone interviews, and/or web-based data entry portal.
III. PROTECTION OF HUMAN RESEARCH PARTICIPANTS
IRB approval to conduct the study has been obtained at all participating sites.Risks are minimized by employing the screening criteria for enrollment into the study, thorough training of the research team in the protection of human research participants, training of site research assistants in recognizing emotional distress and responding appropriately, and implementing and evaluating procedures to ensure confidentiality throughout the study and beyond.To reduce any emotional distress caused by answering questions during the data collection processes, participants are told that they can decline to answer any questions.To ensure protection of confidentiality, all study personnel are carefully trained about the importance of confidentiality and are required to complete instruction/education on human research participant protection. All forms are stored in a secure location. Questionnaire data completed via website portal are encrypted using modern technologies and accessible only by password. A password-protected study directory is established for all database files and analysis files. All databases are cleaned, verified, archived with documentation and then used to create documented statistical analysis files. Access is available only by password and only to study staff. Complete backups of the database files are made on a weekly, monthly, quarterly, and yearly basis. No participant identifying information is linked to patient results. Each study participant is assigned a unique study identification number. For the purposes of retention, we also collect name, address, day and evening telephone numbers, and alternate contact information for each enrolled participant. Such tracking information is stored in a separate database. Throughout the study, we notify participants of any new information that may become available and that might affect their decision to remain in the study.