Mood, body image, fear of kidney failure, life satisfaction, and decisional stability following living kidney donation: Findings from the KDOC study.

Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.

Outpatient Management of Delayed Graft Function Is Associated With Reduced Length of Stay Without an Increase in Adverse Events.

Delayed graft function (DGF) is a common and costly complication of kidney transplantation. In July 2011, we established a multidisciplinary DGF clinic managed by nurse practitioners to facilitate early discharge and intensive management of DGF in the outpatient setting. We compared length of stay, 30-day readmission, acute rejection, and patient/graft survival in 697 consecutive deceased donor kidney transplantations performed between July 2009 and July 2014. Patients were divided into three groups: no DGF (n = 487), DGF before implementation of the DGF clinic (n = 118), and DGF clinic (n = 92). Baseline characteristics including age, gender, panel reactive antibody, retransplantation rates, HLA mismatches, induction, and maintenance immunosuppression were not significantly different between pre- and post-DGF clinic groups. Length of stay was significantly longer in pre-DGF clinic (10.9 ± 6.2 vs. 6.1 ± 2.1 days, p < 0.001). Thirty-day readmission (21% vs. 16%), graft loss (7% vs. 20%), and patient death (2% vs. 11%) did not differ significantly between pre- and post-DGF clinic. Patients in the DGF clinic were less likely to develop acute rejection (21% vs. 40%, p = 0.006). Outpatient management of DGF in a specialized clinic is associated with substantially shorter hospitalization and lower incidence of acute rejection without significant difference in 30-day readmission or patient and graft survival.

Direct and Indirect Costs Following Living Kidney Donation: Findings From the KDOC Study.

Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman's ρ = 0.26, p < 0.001), lower household income (Spearman's ρ = -0.25, p < 0.001), and more unpaid work hours missed (Spearman's ρ = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large.

In kidney transplant recipients with BK polyomavirus infection, early BK nephropathy, microvascular inflammation, and serum creatinine are risk factors for graft loss.

BACKGROUND: Little information is available on the risk factors for graft loss in kidney transplant recipients with BK polyomavirus (BKPyV) nephropathy (BKVN) in the presence or absence of antibody-mediated rejection (AMR). METHODS: We examined the risk factors for graft loss in consecutive kidney allograft recipients with biopsy-confirmed BKVN, with or without concomitant AMR. RESULTS: A total of 1904 kidney transplants were performed at our institution during 2005-2011. Of these, 330 (17.33%) were diagnosed with BKPyV viremia, and 69 were diagnosed with BKVN (3.6%). Eleven patients had a concomitant diagnosis of AMR. Patients with AMR were characterized by significantly higher peak panel-reactive antibody, retransplant rates, and desensitization preconditioning at the time of transplantation, as well as microvascular inflammation (MVI = glomerulitis + peritubular capillaritis), C4d score, and donor-specific antibody at the time of diagnosis (P ≤ 0.01). Treatment with plasma exchange, intravenous immunoglobulin, and cidofovir was more prevalent in this group (P ≤ 0.02). Univariate analyses assessing the risk factors for graft loss in all patients with BKVN, identified an independent association of African-American race, deceased-donor transplantation, serum creatinine (Scr), MVI, and early disease (BKVN within 6 months of transplant) with poor outcomes. Multivariate analyses retained only 3 variables: Scr >2 mg/dL (hazard ratio [HR] = 4.3, 95% confidence interval [CI] 1.9-9.7, P = 0.0004), early BKVN (HR = 2.7, 95% CI 1.3-5.3, P = 0.004), and MVI (HR = 1.8, 95% CI 1.2-2.8, P = 0.008). CONCLUSIONS: These observations suggest that, in patients with BK infection, early BKVN, Scr >2, and MVI are predictors of poor outcomes. Further studies are needed to determine effective treatment strategies for BKVN, with or without AMR.

The independent living donor advocate: a guidance document from the American Society of Transplantation's Living Donor Community of Practice (AST LDCOP).

The independent living donor advocate (ILDA) serves a mandated and supportive role in the care of the living organ donor, yet qualifications and role requirements are not clearly defined. Guidance comes from Centers for Medicare and Medicaid Services (CMS) Conditions for Transplant Center Participation and interpretive guidelines, Organ Procurement and Transplantation Network (OPTN) Policy and CMS and OPTN site surveys, yet interpretation of regulations varies. Herein, the AST Living Donor Community of Practice (LDCOP) offers seven recommendations to clarify and optimize the ILDA role: (a) the ILDA must have a certain skill set rather than a specific profession, (b) the ILDA must be educated and demonstrate competence in core knowledge components, (c) the ILDA's primary role is to assess components of informed consent, (d) centers must develop a transparent system to define ILDA independence, (e) the ILDA should have a reporting structure outside the transplant center, (f) the ILDA's role should be integrated throughout the donor care continuum, (g) the ILDA role should include a narrow "veto power." We address controversies in ILDA implementation, and offer pathways to maximize benefits and minimize limitations of approaches that may each meet regulatory requirements but confer different practice benefits. We propose a research agenda to explore the impact of the ILDA.

Critical Factors Associated With Missing Follow-Up Data for Living Kidney Donors in the United States.

Follow-up care for living kidney donors is an important responsibility of the transplant community. Prior reports indicate incomplete donor follow-up information, which may reflect both donor and transplant center factors. New UNOS regulations require reporting of donor follow-up information by centers for 2 years. We utilized national SRTR data to evaluate donor and center-level factors associated with completed follow-up for donors 2008-2012 (n = 30 026) using multivariable hierarchical logistic models. We compared center follow-up compliance based on current UNOS standards using adjusted and unadjusted models. Complete follow-up at 6, 12, and 24 months was 67%, 60%, and 50% for clinical and 51%, 40%, and 30% for laboratory data, respectively, but have improved over time. Donor risk factors for missing laboratory data included younger age 18-34 (adjusted odds ratio [AOR] = 2.03, 1.58-2.60), black race (AOR = 1.17, 1.05-1.30), lack of insurance (AOR = 1.25, 1.15-1.36), lower educational attainment (AOR = 1.19, 1.06-1.34), >500 miles to center (AOR = 1.78, 1.60-1.98), and centers performing >40 living donor transplants/year (AOR = 2.20, 1.21-3.98). Risk-adjustment moderately shifted classification of center compliance with UNOS standards. There is substantial missing donor follow-up with marked variation by donor characteristics and centers. Although follow-up has improved over time, targeted efforts are needed for donors with selected characteristics and at centers with higher living donor volume. Adding adjustment for donor factors to policies regulating follow-up may function to provide more balanced evaluation of center efforts.

Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus.

This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of ramipril on urinary protein excretion in renal transplant patients treated with sirolimus following conversion from a calcineurin inhibitor. Patients received ramipril or placebo for up to 6 weeks before conversion and 52 weeks thereafter. Doses were increased if patients developed proteinuria (urinary protein/creatinine ratio ≥0.5); losartan was given as rescue therapy for persistent proteinuria. The primary end point was time to losartan initiation. Of 295 patients randomized, 264 met the criteria for sirolimus conversion (ramipril, 138; placebo, 126). At 52 weeks, the cumulative rate of losartan initiation was significantly lower with ramipril (6.2%) versus placebo (23.2%) (p < 0.001). No significant differences were observed between ramipril and placebo for change in glomerular filtration rate from baseline (p = 0.148) or in the number of patients with biopsy-confirmed acute rejection (13 vs. 5, respectively; p = 0.073). One patient in the placebo group died due to cerebrovascular accident. Treatment-emergent adverse events were consistent with the known safety profile of sirolimus and were not potentiated by ramipril co-administration. Ramipril was effective in reducing the incidence of proteinuria for up to 1 year following conversion to sirolimus in maintenance renal transplant patients.

Predonation Direct and Indirect Costs Incurred by Adults Who Donated a Kidney: Findings From the KDOC Study.

Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate's family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them.

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.

Disclosing recipient information to potential living donors: preferences of donors and recipients, before and after surgery.

Consensus guidelines, while recommending that potential living donors should be given information that could impact their donation decision, are nonspecific about the types of information that should be disclosed. We surveyed potential (n = 36) and past (n = 45) living donors and transplant candidates (n = 45) and recipients (n = 45) about their preferences for sharing or knowing specific information about the recipient, how this information would impact decision-making, and who should be responsible for disclosing information. Potential donors were less likely than all others to feel that recipient information should be disclosed to potential donors. Donors and recipients felt most strongly about disclosing if the recipient lost a previously transplanted kidney due to medication nonadherence as well as the likelihood of 1- and 5-year graft survival. Most donors would be less likely to pursue donation if the recipient lost a previously transplanted kidney due to medication nonadherence or generally had problems with taking medications as prescribed. Transplant programs should consider how to best balance the potential donor's right to receive information that could reasonably be expected to affect their decision-making process with the recipient's right to privacy and confidentiality.

B7-1 or B7-2 is required to produce the lymphoproliferative phenotype in mice lacking cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).

The costimulatory molecules B7-1 and B7-2 regulate T lymphocyte activation by delivering activating signals through CD28 and inhibitory signals through cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). The importance of CTLA-4-mediated inhibition was demonstrated by the uncontrolled T cell activation and lymphoproliferative disease that develops in CTLA-4-deficient (-/-) mice. To examine the role of B7 signaling in the activation of CTLA-4-deficient T cells, we bred CTLA-4(-/-) mice with mice lacking B7-1, B7-2, or both B7 molecules. The CTLA-4/B7-1(-/-) and the CTLA-4/B7-2(-/-) mice develop lymphoproliferation and enhanced T cell activation. Mice lacking CTLA-4, B7-1, and B7-2 have a normal life-span, and do not have lymphocytic infiltrates in any organs, or increased T cell activation. Therefore, the two B7 molecules have overlapping functions, since either B7-1 or B7-2 alone can cause the CTLA-4(-/-) phenotype. Elimination of both B7-1 and B7-2 from the CTLA-4- deficient mouse abrogates the lymphocyte activation and disease, and does not reveal evidence for additional stimulatory CD28 ligands. The CTLA-4(-/-) phenotype can be reproduced with anti-CD28 antibody in mice lacking CTLA-4, B7-1, and B7-2, but wild-type mice are unaffected by the same treatment. This suggests that the inhibitory function of CTLA-4 can overcome strong CD28-mediated signaling in vivo.

Molecular basis for leukocyte integrin alpha(E)beta(7) adhesion to epithelial (E)-cadherin.

Cadherins are expressed in tissue-restricted patterns and typically mediate homophilic adhesion. Cadherins also mediate lymphocyte adhesion, providing the opportunity for lymphocyte attachment to parenchymal cells. The best characterized example of lymphocyte adhesion to a tissue-specific cell adhesion molecule, as opposed to a vascular endothelial adhesion molecule, is the interaction between integrin alpha(E)beta(7) on intraepithelial lymphocytes and E-cadherin on epithelial cells. However, the molecular basis for an integrin-cadherin interaction is not well defined. Realization that the cadherin domain adopts a topology similar to the immunoglobulin (Ig) fold suggested that integrin recognition of E-cadherin might be similar to recognition of Ig superfamily ligands. Thus, we modeled domain 1 of human E-cadherin and studied the role of solvent-exposed loops that connect Ig-like core-forming beta strands. Mutational analyses localized the integrin alpha(E)beta(7) recognition site to the top of domain 1 at the face formed by the BC and FG loops, a site distinct from the region recognized in intercellular adhesion molecule (ICAM)-1, -2, and -3, mucosal addressin cell adhesion molecule 1 (MAdCAM-1), vascular cell adhesion molecule 1 (VCAM-1), and fibronectin by their integrin ligands. Moreover, the integrin alpha(E)beta(7) binding site is distinct from the homophilic binding site on E-cadherin. These studies provide a conceptual basis for integrin-cadherin binding and extend the model that an Ig-like fold can serve as a scaffold for recognition.

Successful DCD kidney transplantation using early corticosteroid withdrawal.

Organs from donors after cardiac death (DCD) are being increasingly utilized. Prior reports of DCD kidney transplantation involve the use of prednisone-based immunosuppression. We report our experience with early corticosteroid withdrawal (ECSW). Data on 63 DCD kidney transplants performed between 2002 and 2007 were analyzed. We compared outcomes in 28 recipients maintained on long-term corticosteroids (LTCSs) with 35 recipients that underwent ECSW. DGF occurred in 49% of patients on ECSW and 46% on LTCS (p=0.8). There was no difference between groups for serum creatinine or estimated GFR between 1 and 36 months posttransplant. Acute rejection rates at 1 year were 11.4% and 21.4% for the ECSW and LTCS group (p=0.2). Graft survival at 1 and 3 years was 94% and 91% for the ECSW group versus 82% and 78% for the LTCS group (p>or=0.1). Death censored graft survival was significantly better at last follow-up for the ECSW group (p=0.02). Multivariate analysis revealed no correlation between the use of corticosteroids and survival outcomes. In conclusion, ECSW can be used successfully in DCD kidney transplantation with no worse outcomes in DGF, rejection, graft loss or the combined outcome of death and graft loss compared to patients receiving LTCS.

Sirolimus oral ulcer with Cedecea davisae superinfection.

Cedecea davisae is a member of the Enterobacteriaceae family and is an uncommon pathogen. This organism has been isolated from the blood, sputum, and cutaneous ulcers of only a handful of patients, most of these being elderly or otherwise medically compromised. This is a report of a patient, status post renal transplantation, who developed an oral ulcer associated with sirolimus use and superinfected with C. davisae. According to the literature, this is the first case of C. davisae detected in the oral cavity. Antibiotic therapy led to prompt resolution of this very large ulcer.

Very Early Cytomegalovirus Infection After Renal Transplantation: A Single-Center 20-Year Perspective.

BACKGROUND: Cytomegalovirus (CMV) infection risk in the first month after transplantation is felt to be minimal; however, the epidemiology has not been specifically investigated, particularly in the modern era of potent immunosuppressive regimens and universal CMV prophylaxis. OBJECTIVE: The aim of this study was to describe the incidence of and risk factors associated with CMV occurring less than 30 days after transplant and evaluate the effect of very early CMV on outcomes. METHODS: Retrospective, single-center study of adult renal transplant (RTX) recipients between January 1, 1994 and December 31, 2014. RESULTS: A total of 5225 patients who received a renal transplant in the study time period were reviewed for the presence of CMV infection occurring less than 30 days after transplant. Of these, only 14 patients demonstrated this finding for an overall incidence of 0.27%. Half of these patients were considered to be at heightened risk due to being a recipient of a non-primary transplant or on chronic immunosuppression. This left seven patients without known risk factors for very early CMV to evaluate. In this group, time from transplant to CMV infection was 13.5 ± 7 days. The majority (57.1%, n = 4) were high-risk serostatus (CMV D+/R-) and occurred in the valganciclovir era (71.4%, n = 5). Lymphocyte-depleting induction predominated (57.1%, n = 4). Average cold ischemic time (CIT) was 19.7 ± 7.7 hours. Three patients had post-operative complications, two required exploratory-laparotomy for hemorrhage. When evaluating outcomes, 43% (n = 3) had subsequent episodes of CMV infection, 28.6% (n = 2) developed rejection, and 28.6% (n = 2) died. Outcomes between patients with CMV infection less than 30 days and those with CMV infection more than 30 days after transplant were not significantly different. CONCLUSIONS: In our review of over 5000 kidney transplants, the incidence of CMV infection in the first 30 days after renal transplant is 0.2%. Notable common patient characteristics include hemorrhage requiring re-operation and prolonged CIT. Outcomes were similar to CMV occurring more than 30 days after transplant. This study should provide the clinician with some reassurance; despite potent immunosuppressive therapy, CMV infection in the first 30 days is unlikely.

Investigator Assessment of the Utility of the TruGraf Molecular Diagnostic Test in Clinical Practice.

BACKGROUND: TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. METHODS: In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. RESULTS: When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. CONCLUSIONS: TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.

Application of TruGraf v1: A Novel Molecular Biomarker for Managing Kidney Transplant Recipients With Stable Renal Function.

TruGraf v1 is a laboratory-developed DNA microarray-based gene expression blood test to enable proactive noninvasive serial assessment of kidney transplant recipients with stable renal function. It has been previously validated in patients identified as Transplant eXcellence (TX: stable serum creatinine, normal biopsy results, indicative of immune quiescence), and not-TX (renal dysfunction and/or rejection on biopsy results). TruGraf v1 is intended for use in subjects with stable renal function to measure the immune status as an alternative to invasive, expensive, and risky surveillance biopsies. MATERIALS AND METHODS: In this study, simultaneous blood tests and clinical assessments were performed in 192 patients from 7 transplant centers to evaluate TruGraf v1. The molecular testing laboratory was blinded to renal function and biopsy results. RESULTS: Overall, TruGraf v1 accuracy (concordance between TruGraf v1 result and clinical and/or histologic assessment) was 74% (142/192), and a result of TX was accurate in 116 of 125 (93%). The negative predictive value for TruGraf v1 was 90%, with a sensitivity 74% and specificity of 73%. Results did not significantly differ in patients with a biopsy-confirmed diagnosis vs those without a biopsy. CONCLUSIONS: TruGraf v1 can potentially support a clinical decision enabling unnecessary surveillance biopsies with high confidence, making it an invaluable addition to the transplant physician's tool kit for managing patients. TruGraf v1 testing can potentially avoid painful and risky invasive biopsies, reduce health care costs, and enable frequent assessment of patients with stable renal function to confirm the presence of immune quiescence in the peripheral blood.