RESUMEN
Background: Aiming at understanding whether there are cases of near-tolerance among long-term surviving kidney transplant recipients in our center, or even operant tolerance can be attempted based on their immune status, we analyzed changes of immune cell subsets and cytokines in various groups, and evaluated immune status of long-term survival recipients. Methods: A real-world, observational, retrospective cohort study was conducted in our hospital. Twenty-eight long-term recipients were selected as study subjects, 15 recent postoperative stable recipients, and 15 healthy subjects as controls. T and B lymphocyte subsets, MDSCs, and cytokines were detected and analyzed. Results: Treg/CD4 T cells, total B and B10 cells in long-term and recent renal recipients were lower than healthy controls (HC). The level of IFN-γ and IL-17A in long-term survival patients was obviously higher than that in recent postoperative stable recipients and HC, while TGF-ß1 level was significantly lower in long-term survival group than in short-term postoperative group and HC. Notably, compared with short-term recipients, it has been found that the IL-6 level in both positive and negative HLA groups were obviously lower (all P<0.05). In the long-term survival group, 43% of recipients were positive for urinary protein and 50% were positive for HLA antibody. Conclusion: This "real-world" study validates the findings of real status of long-term survival recipients observed in clinical trials. Contrary to a state of proper tolerance as expected, the group recipients in long-term survival were accompanied by the increased indicators of immune response, while those related to immune tolerance were not significantly increased. Long-term survival recipients with stable renal function may be in an immune equilibrium state where immunosuppression and rejection coexist under the action of low-intensity immune agents. If immunosuppressive agents are reduced or even removed, rejection may occur.
Asunto(s)
Trasplante de Riñón , Humanos , Estudios Retrospectivos , Terapia de Inmunosupresión , Tolerancia Inmunológica , Citocinas/metabolismoRESUMEN
Immunosuppressive therapy is complex and challenging to do correctly due to on-target and off-target side effects. However, it is vital to successful allotransplantation. In this article, we analyzed the critical classes of immunosuppressants used in renal transplantation, highlighting the mechanisms of action and typical clinical applications used to develop predictive models for the diagnosis of various diseases, including the prediction of survival after kidney transplantation. In patients, the authors used a dataset with two immunosuppressants (tacrolimus and cyclosporin). The primary task was investigating critical risk factors associated with early transplant rejection. For this, the censored Kaplan-Meier survival estimation method was used. Our study shows a pairwise correlation between taking and not using a particular immunosuppressant. Therefore, the correct choice of immunosuppressive drugs is necessary to improve the prognosis of transplant survival.
Asunto(s)
Trasplante de Riñón , Humanos , Inmunosupresores/uso terapéutico , Ciclosporina/uso terapéutico , Tacrolimus/uso terapéutico , Terapia de Inmunosupresión , Rechazo de Injerto/tratamiento farmacológicoRESUMEN
Currently, kidney transplantation is the best treatment option for kidney failure for a majority of eligible patients. It is associated with a better quality of life and reduced mortality as compared to staying on dialysis. Many of the improvements in kidney transplant outcomes, observed in recent decades, are due to more efficient immunosuppression strategies. Therefore, developing expertise in the management of immunosuppressive drugs is key to the success of kidney transplantation. In this review, the historical aspects of organ transplant immunosuppression are briefly addressed and the basis of the allograft immune response to contextualize the main topic is provided, which is a deeper view of the immunosuppressive agents, including their known mechanisms of action, pharmacokinetics, interactions, toxicities, and clinical use. The most commonly used immunosuppressive protocols employed based on patients' and donors' characteristics are also presented here.
Asunto(s)
Trasplante de Riñón , Inhibidores de la Calcineurina , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Humanos , Terapia de Inmunosupresión , Inmunosupresores , Calidad de VidaRESUMEN
Renal transplantation is the best treatment for patients with end-stage renal disease. Over the last decades, the introduction of new immunosuppressive agents resulted into the reduction of the incidence of acute rejection and early graft loss. Despite this progress, there has been little improvement in the average life of the transplant. The main reasons of late failure are patient's death due to several complications (e.g. cancer, infectious or metabolic), and progressive deterioration of renal function caused by immunological and non-immunological factors. The immunosuppressive therapy can be distinguished into two components: the induction therapy and the maintenance therapy. The former has the aim to implement intense and immediate immunosuppression. This therapy is mostly useful in transplant with high immunological risk, although it is correlated with an increased risk of cytopenias and viral infections. The latter offers the rationale to prevent organ rejection and minimize drug toxicity. This is generally constituted by the association of two or three drugs with different mechanism of action. The most common application of this scheme includes a calcineurin inhibitor in combination with an antimetabolite and a minimum dose of steroids. Immunosuppressive therapy is also associated to an increased risk of infections and cancer development. For instance, each class of drugs is related to a different profile of toxicity. The choice of treatment protocol should take into account the clinical characteristics of the donor and recipient. Furthermore, this treatment may change anytime when clinical conditions result into complications.