Living donor renal transplantation: recent developments and perspectives.

Renal transplantation is the optimal treatment for patients of all ages with end-stage renal disease. Life expectancy of the population in general is increasing consistently, as is the age of the dialysis population. Consequently, the average ages of kidney donors and recipients are rising. The combination of a growing number of patients with end-stage renal disease and a shortage of organs poses a significant challenge to the transplant community. Donor shortage is associated with unfavorable consequences (e.g. prolonged waiting time, and compromised graft and patient survival). As such, multidirectional efforts are required to expand the donor pool. Increasing the frequency of living donation seems to be an efficient solution. Living donation is associated with superior results for the recipient, and relatively benign long-term outcomes for donors. Reluctance to use organs from living donors whose eligibility was previously considered marginal (e.g. elderly donors) is declining. Although increased donor age is associated with reduced graft survival rates, this should not preclude use of older living donors; transplantation is definitely superior to remaining on dialysis. Thorough, standardized evaluation and careful screening for premorbid conditions in both elderly donors and elderly recipients are essential. Here, we present various options for expanding the living donor pool, with emphasis on the utilization of elderly living donors and transplantation in elderly recipients.

Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs.

Cellular responses to oxygen are increasingly recognized as critical in normal development and physiology, and are implicated in pathological processes. Many of these responses are mediated by the transcription factors HIF-1 and HIF-2. Their regulation occurs through oxygen-dependent proteolysis of the alpha subunits HIF-1alpha and HIF-2alpha, respectively. Both are stabilized in cell lines exposed to hypoxia, and recently HIF-1alpha was reported to be widely expressed in vivo. In contrast, regulation and sites of HIF-2alpha expression in vivo are unknown, although a specific role in endothelium was suggested. We therefore analyzed HIF-2alpha expression in control and hypoxic rats. Although HIF-2alpha was not detectable under baseline conditions, marked hypoxic induction occurred in all organs investigated, including brain, heart, lung, kidney, liver, pancreas, and intestine. Time course and amplitude of induction varied between organs. Immunohistochemistry revealed nuclear accumulation in distinct cell populations of each tissue, which were exclusively non-parenchymal in some organs (kidney, pancreas, and brain), predominantly parenchymal in others (liver and intestine) or equally distributed (myocardium). These data indicate that HIF-2 plays an important role in the transcriptional response to hypoxia in vivo, which is not confined to the vasculature and is complementary to rather than redundant with HIF-1.