Faculty Bibliography

Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insufficiency was associated with transplant failure of whole grafts, which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx.

OBJECTIVE: The purpose of this study was to determine the prevalence and types of renal and extrarenal abnormalities that preclude renal donation or lead to alteration of the surgical approach on the basis of abdominal CT angiography (CTA) in a large group of potential renal donors. MATERIALS AND METHODS: In this retrospective study, 654 potential renal donors undergoing dual-phase CTA were identified from January 2005 to January 2009. The CT reports were systemically reviewed by two radiologists to determine the presence of renal and extrarenal abnormalities. The operative notes of the renal donors were reviewed by one radiologist to determine whether the presence of renal pathology had affected the surgical approach. In the candidates who did not proceed to kidney donation, the reasons that precluded kidney donation were abstracted from the transplant database. RESULTS: Four hundred seventeen potential donors (269 men and 385 women; mean age, 44.0 years; age range, 17-79 years) proceeded to renal donation and 237 did not. The most common renal abnormalities were cysts (34%) and renal stones (4.4%). Renal artery disease was identified in 3.4% of potential donors, including renal artery stenosis, possible fibromuscular dysplasia, and renal artery aneurysm. Suspicious renal masses were incidentally found in 0.5% of potential donors. The most common extrarenal pathology was an incidental adrenal nodule (2.6%). Other significant extrarenal pathology identified included gallbladder mass (0.2%), Crohn disease (0.2%), ovarian mass (0.2%), and possible sarcoidosis (0.2%). Although renal and extrarenal abnormalities were present in 41% of potential renal donors, abnormalities seen on CT only contributed to exclusion of 27 potential donors (4.1%). The most common reason for exclusion was the presence of renal stones or scarring (1.8%). Significant CT findings also contributed to the selection of the right kidney in 29 donors, most commonly due to presence of ipsilateral vascular disease or complex left vascular anatomy. CONCLUSION: Renal parenchymal and vascular abnormalities are common in asymptomatic potential kidney donors. Although most of these represent incidental CT findings, abnormalities can exclude potential renal donors and alter the surgical approach in a small minority of cases.

BACKGROUND: Availability of kidney paired donation (KPD) is increasing in the United States, and a national system through UNOS is forthcoming. However, little is known about attitudes toward KPD among the general public, from which donors (particularly non-directed) are drawn. METHODS: In a national study, we assessed the public's attitudes regarding participation in KPD. RESULTS: Among 845 randomly selected participants, 85.2% of respondents were either "extremely willing" or "very willing" to participate in KPD. Experiences with the medical or organ transplant systems, such as undergoing surgery, having a primary medical provider, a living will, a friend who donated or received an organ, and considering donation after death, were associated with increased willingness. However, increased age, male sex, African American race, Hispanic ethnicity, distrust of the medical system, and not understanding organ allocation were associated with less willingness. CONCLUSIONS: We identify strong support for KPD but some important potential barriers to participation which should be considered as KPD programs are implemented.

BACKGROUND AND OBJECTIVES: ABO-incompatible kidney transplant recipients may have a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO-compatible recipients. It is unclear whether HLA-incompatible recipients share this risk or whether this phenomenon is unique to ABO-incompatible recipients. DESIGN, SETTING, PARTICIPATION, MEASUREMENTS: This study analyzed adult incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by biopsy (per protocol or for cause). This was a retrospective analysis of a prospectively maintained database that compared BKVAN incidence and outcomes between ABO- and HLA-incompatible recipients, respectively. BKVAN link to rejection and graft accommodation phenotype were also explored. The Johns Hopkins Institutional Review Board approved this study. RESULTS: Risk for BKVAN was greater among ABO-incompatible than HLA-incompatible patients (17.7% versus 5.9%; P=0.008). Of BKVAN cases, 42% were subclinical, diagnosed by protocol biopsy. ABO-incompatibility and age were independent predictors for BKVAN on logistic regression. C4d deposition without histologic features of glomerulitis and capillaritis (graft accommodation-like phenotype) on 1-year biopsies of ABO-incompatible patients with and without BKVAN was 40% and 75.8%, respectively (P=0.04). Death-censored graft survival (91%) and serum creatinine level among surviving kidneys (1.8 mg/dl) were identical in ABO- and HLA-incompatible patients with BKVAN (median, 1399 and 1017 days after transplantation, respectively). CONCLUSIONS: ABO-incompatible kidney recipients are at greater risk for BKVAN than HLA-incompatible kidney recipients. ABO-incompatible recipients not showing the typical graft accommodation-like phenotype may be at heightened risk for BKVAN, but this observation requires replication among other groups.

PURPOSE OF REVIEW: Human leukocyte antigen (HLA) sensitization is a major public health problem that limits access to renal transplantation for 30% of the patients awaiting a kidney transplant. This review describes the transplantation modalities available to the sensitized patient and discusses aspects of the donor/recipient phenotypes that determine the most suitable option for a particular patient. RECENT FINDINGS: Patients, who undergo desensitization have a significant survival benefit compared with similar patients, who either remain on dialysis or wait for a compatible donor. The initial donor-specific antibody (DSA) strength is the best predictor of outcome and cost of desensitization. In small, uncontrolled single center trials, complement inhibitors, proteasome inhibitors and anti-CD20 have been used to both prevent and reverse antibody-mediated rejection (AMR). SUMMARY: With new agents being introduced into the armamentarium, which have not undergone rigorous investigation, it is important to emphasize that plasmapheresis, intravenous immunoglobulin, increased sharing, and kidney-paired donation are very effective strategies for transplanting sensitized patients. However, a significant population of patients will not benefit from either kidney-paired donation or desensitization and will require a hybrid technique in which the goal of matching is to reduce the strength of the DSA to facilitate desensitization.

PURPOSE OF REVIEW: To identify factors that affect the choice of route to renal transplantation for the sensitized patient. The evolution of protocols for transplanting sensitized patients has been desensitization (DES), paired donation, and most recently, paired donation combined with DES. Use of these protocols has revealed various factors that influence which route is the most likely to work for a given patient. RECENT FINDINGS: The data indicate that patient blood type and HLA sensitization have the dominant influence on what route is best for a patient but numerous other factors, particularly the number, HLA type, and ABO type of donors a patient brings to a program will also affect the likelihood of transplantation. The distribution of these factors among patients transplanted or unable to find a compatible donor can be used to calculate the probability of transplantation via paired donation. SUMMARY: Kidney paired donation with or without DES provides benefits that cannot be achieved with DES alone. However, DES may provide the fastest route to transplantation.

BACKGROUND: Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). METHODS: We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. RESULTS: Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. CONCLUSIONS: This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.