Research Highlights

Abstract

Molecular Pathways Underlying Adaptive Repair of the Injured Kidney Orlando G, Danger R, Okut H, et al. Ann Surg. Published online July 24, 2018. DOI:10.1097/SLA.0000000000002946. Previous studies have used kidney biopsies for gene expression profiling to gain insights on mechanisms of acute injury. Profiling gene expression in peripheral blood offers a viable alternative strategy. Here, the authors tested, if a noninvasive approach, the expression of genes in peripheral blood, will provide insights into mechanisms of renal transplant repair and regeneration. The authors identified 15 patients who received kidney transplants from either living donors, donors with AKI, or kidneys from donors procured after circulatory death (n = 5, for each group). Because of the nature of AKI and DCD organ donation, many of these allograft recipients experienced delayed graft function. The authors compared gene expression profiles comparing changes after AKI or DCD donation compared with those in LD kidney recipients. Total RNA was isolated from peripheral blood and evaluated for quantity and quality. A comparative analysis of longitudinal peripheral blood gene expression was performed. This analysis revealed 2 gene clusters known to be involved in kidney development and repair with significant differences between LD and AKI/DCD samples. Notably, gene expression clusters remained elevated through the first week after in recipients of AKI or DCD donor grafts, suggesting a role for additional repair and regeneration activities. An analysis of longitudinal patterns showed that a large number of genes were upregulated from pretransplantation to 5 days posttransplant. By day 28 to day 30, most of the transcripts' expression levels had decreased significantly. Eleven genes were differentially expressed in both AKI and DCD recipients. These transcripts may represent biologically relevant gene targets that differentiate the molecular response in DCD and AKI recipients compared with LD recipients. These data support that the pattern, magnitude, and duration of gene expression changes are graft and injury-specific while providing information regarding molecular pathways and specific transcripts that are involved in injury and repair. These results provide further evidence that measuring gene expression in whole blood may represent a convenient and biologically relevant approach to monitoring kidney transplant patients. Analyses of the Short- and Long-term Graft Survival After Kidney Transplantation in Europe Between 1986 and 2015 Coemans M, Susal C, Dohler B, et al. Kidney Int. Published online July 20, 2018. DOI:10.1016/j.kint.2018.05.018. This interesting article presents data on the evolution of kidney transplant outcomes in Europe over the last 3 decades. The authors report on 108 787 transplanted patients documented in the Collaborative Transplant Study, analyzed by a stratified Cox model with a flexible time-dependent effect. Three periods were compared: (1), 1986-1995, (2), 1996-2005 decade, and 3), 2006-2015 thus covering 3 complete decades (1986-2015), reporting the full history of transplant practice since the beginning of its widespread clinical use (after the introduction of cyclosporine). Analyzing survival per decade showed a gradual improvement over each decade reflecting the progress in global posttransplant management. Between 1986 and 1999 improvement was mainly linked to the availability and improved experience in using powerful and innovative immunosuppressive regimens translating into a vastly improved management of alloimmunity and decreasing acute rejection rates. Other factors improving outcomes included an improved control of hypertension, anemia, hypercholesterolemia, and hyperglycemia; more standardized histological evaluation of kidney biopsies; better donor management; improved kidney storage and preservation; updated allocation procedures and (cross) matching techniques; better detection, prevention, and treatment of infections; better management of cardiovascular and urologic complications; moreover, a growing team experience may have contributed to the improvement of graft outcomes. Interestingly, the age of the recipient was inversely related to the hazard of graft failure with younger recipients showing a higher risk of graft failure, indicating that both compliance and immune senescence. There have been striking improvements in graft outcome during the period of 1986 to 1999; more recent developments have shown significant, however, less impressive improvements.