Showing papers by "Anil Chandraker published in 2006"

Polyomavirus-associated nephropathy: update on antiviral strategies.

Abstract: Polyomavirus-associated nephropathy (PVAN) is a major complication of kidney transplantation. Many centers respond to PVAN by reducing immunosuppression. Concern over precipitating rejection, as well as situations in which some PVAN-afflicted individuals have multi-organ transplants, can make reduction of immunosuppression undesirable. In these cases, effective antiviral strategies would be useful. This article describes clinical observations and experiences with 3 different antiviral protocols. Two protocols address antiviral treatment of nephropathy (cidofovir in one, and leflunomide in the other). The third protocol examines fluoroquinolone control of polyoma urinary excretion. Patients responded to all 3 strategies. These promising approaches deserve further evaluation with prospective controlled studies.

Mechanisms and Role of HLA and non-HLA Alloantibodies

Abstract: The role of alloantibodies against HLA and non-HLA targets is becoming increasingly recognized as critical in the pathogenesis of acute and chronic renal allograft outcomes. This review discusses the antigenic targets, the mechanisms of T and B cell activation that result in the production of antibody, the complement cascade, methods of antibody detection, and the evidence that alloantibody-mediated mechanisms are active in acute and chronic rejection.

A prospective study of anaemia and long-term outcomes in kidney transplant recipients

Abstract: Background. Anaemia is prevalent in kidney transplant recipients (KTR), and only few KTR with anaemia receive treatment with erythropoietin. Some have claimed that this undertreatment might contribute to suboptimal outcomes such as mortality and cardiovascular events in these patients. However, no evidence is currently available that anaemia is actually associated with such risks in KTR. Methods. We merged two cohorts of KTR to study the associations between anaemia and two outcomes: all-cause mortality and kidney allograft loss. Detailed information on the demographic and clinical characteristics of these 825 patients was available at baseline. As recommended by the American Society of Transplantation, anaemia was considered present if the haemoglobin concentration was � 13 g/dl in men or � 12 g/dl in women. Patients were followed using the Austrian Dialysis and Transplant Registry. Results. After 8.2 years of follow-up, 251 patients died and 401 allografts were lost. In multivariate analyses, anaemia was not associated with all-cause mortality (HR: 1.08; 95% CI: 0.80–1.45), but it was associated with 25% greater risk of allograft loss (HR ¼ 1.25; 95% CI: 1.02–1.59). This association was even more pronounced in death-censored analyses. Analyses using haemoglobin as a continuous variable or in categories also found no association with mortality. Conclusions. Anaemia may not be associated with mortality in KTR. In light of the recent findings of increased mortality in chronic kidney disease patients with higher haemoglobin treatment target, further evidence is needed to guide clinicians in the treatment of anaemia in these patients.

Modifying graft immunogenicity and immune response prior to transplantation: potential clinical applications of donor and graft treatment.

Abstract: Many studies have shown a strong association between initial graft injury and poor long-term graft outcome. Events initiated by unspecific immune-activating processes including brain death and ischemia/reperfusion injury occurring prior to transplantation reduce graft functionality and amplify the host immune response. These events may be particularly relevant for less than optimal grafts with reduced resistance to unspecific injuries. Several approaches to ameliorate immune activation of the graft by treating the donor or the graft have been studied. While various substances have been shown to have protective effects in experimental transplantation, only a few drugs have been tested clinically and have demonstrated beneficial effects. We review the results of experimental and clinical studies on donor or graft immunomodulation prior to transplantation and analyze the evidence to support clinical application of these strategies.

BK viral reactivation in cardiac transplant patients: evidence for a double-hit hypothesis.

Abstract: Background BK nephropathy is a significant cause of renal dysfunction in renal allograft recipients. The question of whether BK viral infection plays a role in renal dysfunction in cardiac transplantation patients remains to be answered. Methods We prospectively examined the prevalence of BK viral reactivation in the setting of cardiac transplantation and performed a cross-sectional analysis of 111 cardiac transplantation patients. We also assessed the prevalence of viremia in a cohort of 29 renal transplant recipients. Results We found urinary decoy cells in 28 cardiac transplantation patients. Of these, 14 patients had evidence of BK viral DNA in the urine. None, however, had evidence of BK viremia. Mean age, gender, levels of pre- and post-transplant serum creatinine, cardiopulmonary bypass time, and ischemic time were not significantly different between the groups. We found that 7 of 29 renal transplant recipients studied had BK viral DNA in their urine. Conclusion These findings are evidence of BK virus reactivation in the setting of cardiac transplantation at a percentage similar to that seen in renal allograft recipients. In contrast to renal allograft recipients, none had evidence of viremia. Thus, even in the setting of established BK virus reactivation, immunosuppression in combination with renal allograft dysfunction and renal ischemic injury is usually insufficient to cause BK viremia and nephropathy, and it appears that a second, organ-specific hit is necessary, such as kidney inflammation, kidney ischemia, or donor-recipient human leukocyte antigen mismatch.

Induction Therapy: Are We Picking Our Battles?

Abstract: Over the past 10 years the number of patients receiving induction therapy before transplantation has increased dramatically. United Network for Organ Sharing data indicate that while 8.6% of kidney transplants recipients received an induction agent in 1992, the percentage had increased to 59.7% by 2001 and continues to rise (1). The most popular induction agents currently being used are anti-thymocyte globulin, anti-IL-2 receptor antibodies, and most recently the anti-CD52 antibody, alemtuzumab, also known as Campath-1H. While induction therapy has become more popular, several questions regarding the efficacy of different agents as well as the long-term consequences of induction therapy remain to be answered. The popularity of induction therapy has stemmed from its ability to tame the initial immune response, reducing the chances of acute rejection while lowering maintenance immunosuppression. The downside to induction therapy has been the increased potential for malignancies and infections, which is harder to quantify but still needs to be considered a very serious risk. Both recipient and donor populations have continued to change over recent years, with an increasing trend to transplant older patients who have …

Does belatacept provide equivalent suppression of acute renal transplant rejection to ciclosporin

Abstract: Does belatacept provide equivalent suppression of acute renal transplant rejection to ciclosporin?