Summary of FDA workshop on ischemia reperfusion injury in kidney transplantation.

The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention. Animal models evaluating specific pathophysiological pathways were presented, as were the limitations of extrapolating animal results to humans. Clinical trials of various drug products administered in the peri-transplant period were summarized; a few demonstrated early improvements in DGF, but none demonstrated an improvement in late graft function. Clinical trial design for IRI and DGF were also discussed.

Summary of FDA antibody-mediated rejection workshop.

The Food and Drug Administration (FDA) held an open public workshop in June 2010 to discuss the current state of science related to antibody-mediated rejection (AMR) in kidney transplantation. Desensitization, acute AMR and chronic AMR (CAMR) were considered in the context of clinical trial design. Participants discussed experiences with HLA antibody detection and quantitation and the utility of monitoring donor-specific antibodies (DSAs) to inform the management of patients with AMR. The role for animal models was discussed. Diagnostic and prognostic features of histology were presented, followed by discussion of sensitivity and specificity of various criteria. The published literature on treatment of acute AMR was summarized, which consisted of case series and limited data from controlled clinical trials. Considerations for future clinical trials were presented, including endpoints and statistical evaluations of outcome. Although many issues need further consideration, the meeting enabled an important exchange of ideas between experts in the field.

Hydroxyproline and total protein levels in gingiva from patients treated with phenytoin and cyclosporine-A.

Hydroxyproline (Hyp) and total protein levels were studied in gingiva from patients treated with phenytoin (PHT) and cyclosporine-A (CSA). The study included 5 groups of subjects: PHT and CSA groups with and without gingival overgrowth (PHT-GO+), (PHT-GO-), (CSA-GO+), (CSA-GO-), and periodontally healthy controls (C). After taking clinical measurements, gingival samples were harvested by gingivectomy or excising one or two papillae from the posterior areas. The samples were analyzed biochemically. In the PHT groups, both Hyp and total protein levels were significantly higher than in the C group. The differences between the PHT-GO+ and PHT-GO- groups were not statistically significant. In the CSA groups, total protein levels were significantly higher than in controls while no significant difference was found in Hyp levels. The differences between the CSA-GO+ and CSA-GO- groups were not statistically significant. When the PHT and CSA groups were compared, Hyp levels were significantly higher in the PHT-GO+ group than in the CSA-GO+ group. Total protein level differences between the PHT and CSA groups were not statistically significant. Correlations between age, plaque index, gingival overgrowth index, Hyp and total protein levels were analyzed and most were found not to be statistically significant. PHT appears to stimulate both collagen and total protein synthesis in gingiva while CSA seems to have a stronger effect on total protein synthesis. This suggests that the mechanisms underlying PHT- and CSA-induced gingival overgrowth are different and further comparative studies are needed.