Date Published: March 25, 2019
Author(s): Kristin Mai, Andreas Boldt, Hans-Michael Hau, Michael Kirschfink, Stephan Schiekofer, Frieder Keller, Joachim Beige, Athanassios Giannis, Ulrich Sack, Franz Maximilian Rasche.
Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft.
Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFβ, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD.
Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p < 0.001) and an increase in CD25+ T cells (p = 0.026), sCD30 (p < 0.001), HLA-DR+ regulatory T cells (p = 0.005), and regulatory T cells (p = 0.003). TGFβ and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.
Today, the dramatic descent of the frequencies of deceased kidney transplantations is determined by a decrease in the willingness for donating a deceased kidney and supported by strict political and legal conditions [1–4]. Therefore, the elimination of possible interfering or harming events to prevent acute rejections and to achieve an optimal conditioned organ in the highly complicated process of kidney transplantation is the main issue nowadays.
In this prospective study, we examined for the first time the relevant immunologic effects induced by HD with newer polynephron membranes which may have an impact on the outcome of renal allografts (Figure 2 and Table 5 [10–14, 16, 18]).
In CKD5D patients of our study, frequencies of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells were increased and frequencies of naïve CD8+ T cells were decreased. The concentration of sCD30—a biomarker used to predict rejection—was elevated in our patients and further increased during HD. HD increased regulatory T cells, decreased CD4- CD8- T cells, and causes a biphasic course with either a transient decline (natural killer T cells, CD8+ HLA-DR+ T lymphocytes, activation of the complement system, and higher concentration of TGFβ) or a transient increase (CD4+ T lymphocytes, CD4+ HLA-DR+ T lymphocytes). The results of our data suppose that in the first hours after the beginning of the HD intercurrent changes will be remarkable. This normalizes until the fourth hour. Therefore, we argue not to consider short-time dialysis before kidney transplantation. Further studies will be necessary with a detailed focus on the complement system, biocoating, and a follow-up of these patients after renal transplantation.