Publications Archive

Alport Syndrome is an X-linked progressive glomerular basement disorder with a prevalence of 1/50,000 live births. This retrospective analysis of data reported to the Organ Procurement Transplant Network examines outcomes associated with the disease.

Since 2000, despite the shortage of kidneys from deceased donors for transplantation, only about 100 kidney transplants each year were performed with donors older than age 70. Kidneys from these older donors represent only 6% of those allocated in the United States as expanded criteria donors. In this study, we examine how these kidneys might be optimally utilized.

The 20-60 simultaneous heart-kidney (SHK) transplants performed in the United States every year provide a unique setting for comparing transplant care provided by nephrologists and cardiologists. This study examines rates of heart and kidney rejection and graft loss in the thoracic and kidney analytic files provided by the Organ Procurement Transplant Network.

As a possible consequence of public disclosure of center survival rates in the United States, organs from consenting donors may not be utilized because of a low expected benefit to the recipient. This study examines the reasons for non-utilization with the aim of identifying characteristics of organs not suitable for transplantation in the United States, which could possibly be implanted elsewhere.

IL-6 is a key pro-inflammatory cytokine unregulated after Brain Death (BD) in humans. It leads to adhesion molecule activation and leukocyte invasion in all organs. Pre-explantation organ dysfunction is a direct consequence of inflammation, and renders many organs unsuitable for transplantation. Functionally, IL-6 elevation correlates with deteriorating donor cardiac function in humans and its unregulation in kidney and liver donors worsens ischemia-reperfusion injury in recipients. Etc.

Gastrointestinal (GI) symptoms are the most common complications with mycophenolic acid (MPA) therapy. MRP2 and UGT2B7 which are involved in the excretion and production of the metabolites of MPA respectively may play a role in the presentation of GI symptoms.

Recent advances in vector technology now allow the possibility of genetically engineering graft tissues to express reduced levels of HLA. Reducing HLA expression could help to overcome the limitations imposed by polymorphisms which restrict availability of suitable donors, complicate logistics of procuring and delivering matched tissues and organs, and necessitate life-long immunosuppression. We have previously shown that lentiviral vectors can be used to deliver short hairpin RNAs (shRNA) that knock down HLA expression in a class- or allele-specific manner in established human cell lines, and thereby allow evasion from immune recognition by alloreactive T cells. Here we have further characterized and quantitated the effects of dose-dependent gene transfer and shRNA-mediated knockdown of HLA in human cell lines and primary cells on their ability to be recognized by alloreactive cytotoxic T lymphocytes (alloCTL).

The development of diabetes after transplantation is a significant problem that dramatically increases patient morbidity and mortality. The principle cause of NOPTDM is the use of diabetogenic drugs, especially steroids and calcineurin inhibitors (CNIs), and yet only a proportion of recipients develop the disease. This suggests an individuality in susceptibility that may have a genetic component.

It is very important to investigate whether specific pediatric allocation schemes can not only lead to minimization of waiting time, but also to better clinical outcomes for children with end-stage renal disease (ESRD).

HLA matching is important and necessary for renal and bone marrow transplants (Curr Opin Organ Transpl 2004 9:1-7, NEJM 1990.323:1818-1822). Zero-mismatched renal transplants are associated with fewer rejection episodes and longer graft survival, and require less immunosuppression. In adult bone marrow transplantation, it is necessary to have no more than one allele mismatch to obtain maximum engraftment and minimize graft vs host disease. siRNA is a ubiquitous regulatory system which selectively inhibits gene expression; accordingly, we investigated whether siRNA mediated knockdown of Class I HLA would enable allogeneic cells to evade immune recognition.