Faculty Bibliography

PURPOSE: Retrorsine selectively inhibits hepatocyte proliferation and following liver injury evokes small hepatocyte-like progenitor cells. The aim of this study is to find out whether endogenous extrahepatic cells contribute to small hepatocyte-like progenitor cells after retrorsine treatment. METHODS: Wild-type Lewis rat liver exposed to retrorsine was transplanted into GFP transgenic Lewis rat. GFP positive, albumin-producing polygonal cells were expected as reciepient-derived hepatocyte-like cells. RESULTS: Four weeks after transplantation of 50% volume of retrorsine-pretreated liver, the rate of GFP positive hepatocyte-like cells was 0.02365%. Majority of these cells resided as single cells and their cell size was significantly larger than that of normal hepatocytes (mean cell size; 799.4 um(2) vs. 451.3 um(2), p<0.0001). At eight weeks, clusters of GFP positive small-size albumin-producing cells appeared and occupied 0.00759% of hepatocytes. The morphology of these cells was similar to that of small hepatocyte-like progenitor cells, 12.5% of them were Ki67 positive, majority of them were negative for CYP1A2 staining, and some clusters contained larger cells indicating further maturation. CONCLUSION: Endogenous extrahepatic cells can form a cluster of small cells resembling small hepatocyte-like progenitor cells in a transplanted retrorsine-pretreated liver. The contribution of extrahepatic cells to liver mass maintenance is quite low and its importance is unclear.

A component necessary for successful transplantation of the sensitized patient is timely and high quality support from the histocompatibility laboratory that helps guide selection of the best route to transplantation and the clinical care of the patient. Responsibilities of the laboratory include risk assessment, HLA typing, and accurate antibody characterization.

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.

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.