Showing papers by "Robert J. Stratta published in 2010"

Clinical Operational Tolerance After Renal Transplantation: Current Status and Future Challenges

Abstract: In solid organ transplantation, the achievement of an immunosuppression (IS)-free state [also referred to as clinical operational tolerance (COT)] represents the ultimate goal. Although COT is feasible and safe in selected cases after liver transplantation, it is an exceptional finding after other types of solid organ transplantation. In the field of renal transplantation (RT), approximately 100 cases of COT have been reported to date, mainly in patients who were not compliant with their immunosuppressive regimens or in individuals who had previously received a bone marrow transplant for hematological disorders. On the basis of promising results obtained in animal models, several tolerogenic protocols have been attempted in humans, but most have failed to achieve robust and stable COT after RT. Molecule-based regimens have been largely ineffective, whereas cell-based regimens have provided some encouraging results. In these latter regimens, apart from standard IS, patients usually receive perioperative infusion of donor bone marrow-derived stem cells, which are able to interact with the immune cells of the host and mitigate their response to engraftment. Unfortunately, most renal transplant patients who developed acute rejection-occurring either during the weaning protocol or after complete withdrawal of IS-eventually lost their grafts. Currently, the immune monitoring necessary for predicting the presence and persistence of donor-specific unresponsiveness is not available. Overall, the present review will provide a conceptual framework for COT and conclude that stable and robust COT after RT remains an elusive goal and that the different strategies attempted to date are not yet reproducibly safe or effective.

The pancreas allograft donor: current status, controversies, and challenges for the future

Abstract: The pancreas allograft is a scarce resource that is currently underutilized. The selection of appropriate deceased donors for pancreas procurement is of paramount importance for minimizing technical failure and optimizing long-term outcomes in pancreas transplantation. Despite the increasing demand for pancreas transplantation, increases in overall organ donation rates and the evolution of criteria that constitute an "acceptable" pancreas donor, the number of deceased donor pancreas transplants being performed in the United States has actually declined in recent years. Although there are many factors that must be considered during evaluation of the potential pancreas allograft donor to minimize morbidity and graft loss, it is evident that there are transplantable organs that are not used. In this review, deceased donor pancreas identification, management, selection, allocation, assessment, preservation, and the problem of pancreas underutilization will be discussed.

Relationship between assays of glycemia in diabetic subjects with advanced chronic kidney disease.

Abstract: Background: Relative to hemoglobin A1c (HbA1c), glycated albumin (GA) more accurately reflects recent glycemic control in diabetic patients on hemodialysis and

Renal Allograft Failure Due to Emphysematous Pyelonephritis: Successful Non-Operative Management and Proposed New Classification Scheme Based on Literature Review

Abstract: Emphysematous pyelonephritis (EPN) is a rare necrotizing infection of the kidney caused by gas-forming organisms, usually occurs in diabetic patients, and often requires nephrectomy for effective therapy. EPN is rarely reported in renal allografts, with only 20 cases found in the English literature. We report herein a case of EPN in a transplanted kidney resulting in acute renal failure and sepsis. The patient was managed non-operatively with subsequent recovery of renal allograft function. Based on this experience and a review of the literature, we suggest an amended classification system for EPN in kidney transplantation to plan and guide treatment options accordingly. However, the scarcity of this disease process, coupled with the lack of prospective validation of the new classification scheme, prevents drawing definitive conclusions regarding optimal management strategies including the role and timing of allograft nephrectomy.

Defining the Risks for Cytomegalovirus Infection and Disease After Solid Organ Transplantation

Abstract: Cytomegalovirus continues to be one of the most clinically significant infections after solid organ transplantation. Classic definitions of patients at high risk for infection and tissue-invasive disease are focused on recipient-donor serostatus, type of organ transplanted, and overall level of immunosuppression. However, recent trends in clinical practice call for a reevaluation of cytomegalovirus infection risks after solid organ transplantation. Indeed, whereas early-onset cytomegalovirus infection is usually controlled by antiviral prophylaxis with ganciclovir and derivatives, delayed- and late-onset cytomegalovirus infection can develop after the completion of a course of preventive therapy. In addition, indirect effects of cytomegalovirus infection may occur as a result of persistent low-level viremia. Suboptimal dosing of antiviral drugs due to specific drug toxicities may result in the development of ganciclovir-resistant cytomegalovirus disease. The relationship between organ allograft rejection and cytomegalovirus infection and disease has been recognized for some time. Transplantation of increasing numbers of extended-criteria donor organs increases the risk of delayed graft function and acute rejection, prompting the use of more intensive immunosuppression. In addition, the trend to spare long-term exposure to calcineurin inhibitors has contributed to a resurgence in the use of polyclonal T-cell induction immunosuppressive agents, which may reduce host anticytomegalovirus immunity. We discuss the current trends in solid organ transplantation that provide a foundation for defining risks for cytomegalovirus infection and disease, including identification of patients who would benefit from more aggressive cytomegalovirus monitoring and prevention strategies.

Cost-effective immunosuppressive options for solid organ transplantation: a guide to lower cost for the renal transplant recipient in the USA

Abstract: Of the numerous risks associated with immunotherapy for the prevention of rejection, cost is perhaps the most universal. In the USA and some other countries, the costs of immunosuppression make transplantation unavailable for some medically viable transplant candidates, and for others who receive a transplant, the long-term costs are economically crippling. Minimization and tapering of immunosuppression, use of generics, manipulation of metabolism, infection surveillance instead of prophylaxis, and advantageous routes of administration are some strategies that can be employed to reduce immunotherapy expense. Using these strategies, we describe an immunosuppression regimen for kidney transplantation that might be only a third of the cost of current ‘standard’ regimens in the USA. Such a regimen might allow some patients who might not otherwise qualify economically to safely receive a kidney transplant. The purpose of creating an alternative, lower-cost immunotherapy regimen is to give patients a choice. Re...

Short-term renal outcomes in African American and Caucasian donors following live kidney donation.

Abstract: Reeves-Daniel A, Freedman BI, Assimos D, Hartmann EL, Bleyer A, Adams PL, Westcott C, Stratta RJ, Rogers J, Farney AC, Daniel KR. Short-term renal outcomes in African American and Caucasian donors following live kidney donation. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01170.x © 2009 John Wiley & Sons A/S. Abstract: Introduction: Although African Americans (AA) are considered higher risk kidney donors than Caucasians, limited data are available regarding outcomes of AA donors. Methods: We performed a single-center retrospective review of all kidney donors from 1993 to 2007 and evaluated race/ethnic differences in post-donation changes in renal function, incident proteinuria, and systolic blood pressure (SBP) using linear mixed models. Results: A total of 336 kidney donors (63 AA, 263 Caucasian, 10 other) were evaluated. Before donation, AA had higher serum creatinine concentrations, estimated glomerular filtration rate (GFR) values, and SBP levels than Caucasians. No significant changes in SBP or renal function were observed between the two groups within the first year after donation, although results were limited by incomplete follow-up. Conclusion: AA had higher pre-donation serum creatinine, GFR, and SBP values compared to Caucasians; however, the degree of change in renal function and blood pressure did not differ between groups following kidney donation. Although long-term studies are needed, our study suggests that AA and Caucasians experience similar short-term consequences after donation. The incomplete data available on donor outcomes in our center and in prior publications also indicates a global need to implement systems for structured follow-up of live kidney donors.