The Effect of the Gut Microbiota on Transplanted Kidney Function.

The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.

Lack of association of C599T polymorphism in the glutathione peroxidase (GPX1) gene with delayed graft function, acute kidney graft rejection and chronic allograft nephropathy.

BACKGROUND: The glutathione peroxidase/glutathione system is a major defense in oxidative stress. Glutathione peroxidase (GPx) is a selenium-containing antioxidant enzyme that effectively reduces hydrogen peroxide and lipid peroxides to water and lipid alcohols, respectively, and in turn oxidizes glutathione to glutathione disulfide. Previous studies have shown that the activity of glutathione peroxidase is genetically determined and is associated with polymorphisms in GPX1 gene. The aim of the present study was to examine the association between the C599T polymorphism in the glutathione peroxidase (GPX1) gene and delayed graft function of kidney allografts, acute rejection and chronic allograft nephropathy. MATERIAL/METHODS: One hundred eighty-seven recipients of first cadaveric renal transplants from the Department of Nephrology, Transplantology and Internal Medicine of Pomeranian Medical University were included in this retrospective study. Genotyping of C599T polymorphism in the GPX1 gene was performed using PCR-RFLP method. RESULTS: There were no significant associations between this polymorphism and delayed graft function, acute rejection and chronic allograft nephropathy. CONCLUSIONS: The present results suggest that GPX1 C599T polymorphism has no influence on the graft function in the first phase after transplantation, as well as on the acute kidney graft rejection and chronic allograft nephropathy.

Conjugated linoleic acid increases intracellular ROS synthesis and oxygenation of arachidonic acid in macrophages.

OBJECTIVE: Conjugated linoleic acids (CLAs) have potential antiatherosclerotic properties: they may inhibit atherosclerotic processes by reducing the intensity of inflammatory processes. However, in vivo studies have shown that the application of trans-10, cis-12 CLA in obese men increased their oxidative stress. The objective of this study was to determine whether CLA can lead to an increase in oxidative stress and to isoprostane synthesis in macrophages. METHODS: Monocytes from peripheral blood and human monocytic leukemia cells were used in this study. Monocytes were differentiated to macrophages, and were incubated with 30 microM cis-9, trans-11 CLA and trans-10, cis-12 CLA or linoleic acid for 2 days. In some experiments the inhibitors of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) or respiratory chain were added. After incubation, synthesis of reactive oxygen species (ROS), total cellular concentration of adenosine triphosphate, concentration of 8-epi-prostaglandin F2 alpha, activity of cytoplasolic phospholipase A2 (cPLA2), activity of mitochondria, and expression of mRNA of PPAR-alpha were measured. RESULTS: In cells cultured with CLAs intercellular ROS synthesis increased. In this condition the mitochondrial energy potential was high, and the inhibitors of the respiratory chain and PPAR-alpha reduced ROS concentration. At the same time, the cPLA2 activity was abolished. In contrast, 8-iPF2 alpha III synthesis increased in CLA cells. CONCLUSION: Cultivation of cells with CLA leads to an increased ROS synthesis, partly by PPAR-alpha mechanism. An increase in ROS concentration and inhibition of cPLA2 activity can stimulate oxygenation of arachidonic acid and contribute to an increase in 8-epi-PF2 alpha III level and in the apoptosis process in macrophages.