Marc Schiesser

We developed a multicentric Swiss protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. The aim of this study was to assess efficacy and safety of immunoadsorption column reuse in ABO-incompatible kidney transplantation. We performed a multicentric prospective trial including all ABO-incompatible kidney transplantations in Switzerland from 2005 to 2011. Patients received rituximab and standardized immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Antigen-specific perioperative immunoadsorption was performed. Immunoadsorption columns were reused after restoration. Graft survival, patient survival, kidney function, rejections, number of columns, adverse events after column reuse, and anti-A/anti-B antibody titers were assessed. Seventy-one ABO-incompatible patients underwent antigen-specific immunoadsorption and could be transplanted across the blood group barrier. Kaplan-Meier estimates for both, patient-censored and death-censored graft survivals were both 97.2% at 5 years. Allograft function was excellent with a mean estimated glomerular filtration rate of 54 mL per min after 1 year. The median number of pretransplant immunoadsorptions was 5. All centers performed column reuse. A total of 394 immunoadsorption procedures were performed with reused filters. Patient survival, graft survival, and adverse events did not differ when filters were reused. Column reuse resulted in cost savings of 21,458 USD per patient. We have introduced a national protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. Column reuse was efficient and safe.

Ischemia and reperfusion (IR) injury of the liver is associated with impaired bile secretion, but the effects of ischemic preconditioning (IPC) and intermittent ischemia (INT) on bile flow are unknown. A rat model of segmental (60%-70%) hepatic ischemia and reperfusion was employed to test the effects of IPC and INT on bile flow. Continuous clamping for 45 min (CC) substantially reduced bile flow, and this did not recover after 60 min of reperfusion. IPC and INT caused a significant recovery of bile flow. The elevation in plasma liver marker enzymes induced by CC was not reduced by IPC and INT. Light microscopy showed mild hepatocyte damage in all groups. In the CC group, the amount of F-actin localized around the bile canaliculi in the ischemic lobes was less than that in the nonischemic lobes, but this difference was not observed in the IPC and INT groups. It is concluded that IPC and INT substantially alleviate the decrease in bile flow induced by ischemia. Bile flow may be useful in the assessment of IR injury.

Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of this study was to investigate the effects of IPC and INT on ischemia reperfusion injury in aged livers. A rat model of segmental hepatic ischemia (45 min) and reperfusion (60 min) was used. Bile flow, as an indicator of early hepatocyte damage and dynamic liver function, plasma concentrations of bilirubin, liver marker enzymes, and liver histology were assessed. In young rats (8-13 weeks), IPC regimes of 10 min clamping and 10 min reperfusion, and 5 min clamping and 30 min reperfusion, restored bile flow to 23 and 42%, respectively, of the initial value, compared to 14 and 88% for continuous clamping and controls, respectively. An INT regime of three cycles of alternating 15 min perfusion and 15 min clamping gave a substantially greater (70%) restoration of bile flow. In aged rats (20-24 months), the IPC regimes did not give any restoration of bile flow. By contrast, the INT regime restored bile flow to 68%. Plasma bilirubin concentrations were lowest in the INT groups, whereas alanine transaminase concentrations for the IPC and INT groups compared with the continuous clamping groups showed no significant differences. In young rats, INT is more effective than IPC in restoring the immediate consequences of IP-induced damage to hepatocytes and liver function after ischemia-reperfusion. In aged rats INT, but not IPC, reverses hepatocyte damage and restores liver function. INT may promote better hepatocyte and liver function than IPC following the surgical resection of aged livers.