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Renal transplantation is the treatment of choice for many patients with end stage renal disease. While significant progress has been achieved in short-term outcomes, long-term graft survival has only marginally improved. More than 50% of transplanted kidneys from deceased donors fail within ten years; and from living donors, within 12 years. A lack of clinical tools to accurately monitor the allograft is a major causative factor in this lack of progress. This paper discusses newly available methods used to assess allograft status with emphasis on the role of circulating chimerism in renal transplantation as a diagnostic indicator for rejection and injury.

Human renal microvascular endothelial cells (RMEC) express high levels of MHC class II proteins under normal physiologic conditions. They are positioned to interact with circulating leukocytes. Yet, under normal conditions kidney inflammation does not occur. Isolated RMEC can peptide presentation to influenza specific T cells. T cell proliferation and cytokine secretion are blocked by antibodies to CD40, CD58 and HLA-DR; and enhanced by antibodies to PDL1 (B7-H1,CD274). Using cytometry we find high levels of CD58 and CD274 on RMEC in normal human kidneys and CD40 on some RMEC of transplanted kidneys. We hypothesized that RMEC PDL1 interaction with T cell PD-1 (CD279) prevents T cell activation in human kidneys. New PD-1 blocking monoclonal antibodies, such as nivolumab, are being used to treat advanced cancers by selectively blocking PD-1 interactions with ligands PD-L1 (CD274, B7H1) and PD-L2 (CD273, B7H2) present on tumor cells. We have identified four cases of acute kidney injury in patients receiving PD-1 pathway blockade. Biopsies revealed an intense interstitial nephritis in the area of the class II expressing RMEC. Our interpretation of RMEC’s ability to activate T cells in a class II-peptide dependent manner, their high levels of PD-L1 (CD274) and now the development of interstitial inflammation in patients receiving anti-PD1 monoclonal therapy is that RMEC are poised to present peptide from circulating antigen as an immune surveillance system, with the PD1 pathway functioning to restrain T cell activation. Other human organs also express high levels of HLA class II on microvascular endothelial cells. Hence our hypothesis of a kidney capillary endothelium forming an immune surveillance system may also pertain to other organs.