Transplanting the elderly: Balancing aging with histocompatibility.

Across the world, the proportions of senior citizens (i.e. those ≥65years) increase rapidly and are predicted to constitute over 25% of the general population by 2050. In 2012 already 48% of the population with end stage renal disease (ESRD) was aged 65years or older. Transplantation is considered the preferred treatment option for ESRD offering survival advantage over long-term dialysis in the majority of patients. Indeed, acceptable outcomes have been documented for selected patients over the age of 70years or even cases over 80years. The reality of organ scarcity and prolonged waiting times for a deceased donor kidney transplantation, however, indicate that at best 50% of the selected elderly may have realistic expectations to receive a timely transplant offer. By choice or medical selection, access to transplantation also decreases with increasing age. In order to expedite the chance for elderly to receive a kidney transplant dedicated allocation systems have been developed. These allocation systems, like the Eurotransplant Senior Program (ESP), support preferential local allocation of kidneys from older donors to older patients in order to match recipient and graft life while disregarding histocompatibility for HLA antigens. The consequence has been more acute rejection episodes and an increase in immunosuppressive load. In the elderly, the most common cause of graft loss is death with functioning graft and death from infectious diseases is one of the dominant causes. The Eurotransplant Senior DR-compatible Program (ESDP) was designed to further improve the perspective of successful transplantation in the elderly in terms of life and quality of life by re-introducing matching criteria for HLA-DR in the old-for-old algorithm.

Hyaluronic acid uptake in the assessment of sinusoidal endothelial cell damage after cold storage and normothermic reperfusion of rat livers.

The uptake of hyaluronic acid (HA) was used to assess preservation damage to sinusoidal endothelial cells (SEC) during cold storage and subsequent normothermic reperfusion of rat livers. After 8, 16, 24, and 48 h storage in University of Wisconsin (UW) solution, livers were gravity-flushed via the portal vein with a standard volume of cold UW solution containing 50 micrograms/l HA. The effluent was collected for analysis of HA, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). The mean uptake of HA at 0 h was 59.1% +/- 4.6% (mean +/- SEM). After 8 h of storage, HA uptake was similar (55.5% +/- 7.3%), whereas after 16 h of storage it was reduced to 34.7% +/- 5.8%. At 24 and 48 h of storage, no uptake of HA was found. In a second series of experiments, livers were stored in UW solution and subsequently reperfused for 90 min with a Krebs-Henseleit solution (37 degrees C) in a recirculating system containing 150 micrograms/l HA. Following 8 h of storage, 34.6% +/- 8.0% of the initial HA concentration was taken up from the perfusate. After 16 and 24 h of storage, no uptake of HA was found. The results of this study indicate that damage to SEC occurs progressively during storage, leading to zero uptake of HA by the rat livers at 24 h of cold ischemia time. Additional reperfusion injury to the SEC was demonstrated by the reduced ability of the SEC to take up HA following normothermic reperfusion. The uptake of exogenous HA in preserved livers, used as a tool to assess SEC injury, enables the detection of early preservation damage.