Cyclophilin a as a Mediator of Tissue Injure and Nephrotoxicity

Cyclophilin A (CypA) belongs to the peptidyl-prolil isomerase (PPlase) family of proteins and it is also known as the cellular receptor for cyclosporine A (CsA). CsA binds to CypA and inhibits the PPIase activity, but the CypA-CsA complex also binds to calcineurin that promotes the expression of genes encoding cytokines and other proteins required for immune response. In addition, the polymorphism variation of CypA promoter seems to have an influence on the expression of CypA in in vitro studies. CypA was also implicated in inflammatory processes (such as, among others, those observed in rheumatoid arthritis, atherosclerotic disease, nephrotoxicity) and it can be secreted by cells in response to inflammatory stimuli. CypA can also have a role in the molecular mechanisms by which CsA induces nephroxicity but these remain poorly understood. Recent studies suggest that CsA inhibition of CypA PPlase activity is a possible mechanism of this drug toxicity. In addition, CypA overexpression could be protective against CsA nephrotoxicity. Finally, the putative common mechanism by which CypA could be involved in CsA nephrotoxicity and tissue injury is related to its proinflammatory effects in cells.

Early Surgical Complications after Single Kidney Transplantation from Heart-Beating Deceased Donor

To evaluate early surgical complications occurring in the first year after kidney transplantation, and their correlation with one-year patient and graft survival, we retrospectively evaluated 504 single kidney transplantations from heart-beating deceased donors performed in our center from 1993 to 2008. Twenty-seven re-transplanted patients, 10 living related, 8 double kidney, 9 combined liver-kidney, 3 heart-kidney, one heart-kidney-pancreas, and 12 kidney-pancreas transplantations were excluded from our study. Cases of immunological complications, systemic infections or primary disease recurrence were also excluded. There were 25 (4.96%) vascular complications: 3 cases of arterial thrombosis (0.6%), 11 of venous thrombosis (2.18%), and 2 cases of concomitant arterial and venous thrombosis (0.4%). There were 6 cases (1.2%) of arterial rupture due to pseudo-aneurysm; in 3 patients (0.6%) Candida Albicans was diagnosed as principal cause of arthritis. Fortythree (8.5%) patients developed early urinary complications, differentiated in leakage or stenosis. Intestinal complications occurred in 13 cases (2.6%), and 3 patients (0.6%) developed acute pancreatitis. In our series, complicated lymphoceles treated by open or laparoscopic surgery, or by the positioning of a Tenchkoff catheter occurred in 61 patients (12.10%). Median time between diagnosis and treatment was four days (range 1–12 days). Despite early surgical complications, one year patient and graft survival was 95.7% and 85.3%, respectively, similar to patients without complications (96.8% and 87.9%, respectively) (P=0.04). Kidney transplantation is currently considered a safe therapeutic option for endstage renal disease, with low morbidity, and very low mortality. Prompt diagnosis and immediate treatment of early surgical complications can have a positive impact on one-year patient and graft survival.