Project description:Mycophenolic acid is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. Despite its widespread use, there is a clinical need to reduce solid-organ transplant rejection and improve rates of complete therapeutic response in autoimmunity. Single-cell RNA-sequencing (n=6) in lymphocytes was performed at baseline, post-stimulation, and post-mycophenolate treatment. This study identifies a polygenic transcriptomic signature in lymphocyte sub-populations predictive of mycophenolate response.
Project description:Tacrolimus (TAC) is an immunosuppressant widely used in kidney transplantation. TAC displays considerable inter-individual variability in pharmacokinetics (PK). Genetic and clinical factors play important roles in TAC PK. To define genetic factors associated with tacrolimus blood trough concentration, we performed a genome-wide association study of renal transplant samples from 251 Chinese renal transplant recipients. We identified 23 single nucleotide polymorphisms (SNPs) related to TAC PK variability. All 23 genome-wide significant SNPs (p<5E-8) were located on chromosome 7, including rs776746. These findings suggest that these SNPs may be associated with the unexlained TAC PK variability in renal transplant recipients and require further investigation.
Project description:In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft.
Project description:In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft. A single centre, prospective, randomized, open label trial investigating the additional effect of paricalcitol 2ug/day to standard care was performed. Participants were included 8 weeks after engraftment irrespective of PTH-level and followed for 44 weeks. Microarray analyses were performed in kidney biopsies at study end for the investigation of potential effects on gene expression profile. This dataset is part of the TransQST collection.
Project description:Mycophenolic acid (MPA) is a potent inhibitor of the inosine monophosphate dehydrogenase and commonly used as an immunosuppressive drug in transplantation. MPA inhibits proliferation of both T- and B-lymphocytes by guansoin depletion. Since fibroblasts rely on the de novo synthesis of guanosin nucleotides, it is assumed that MPA interacts with fibroblasts causing an increased frequency of wound healing problems. We show a downregulation of the cytoskeletal proteins actin, vinculin and tubulin in human dermal fibroblasts exposed to pharmacologic doses of MPA using microarray technology and western blot. This reduction in protein content is accompanied by a substantial derangement of the cytoskeleton in MPA-treated fibroblasts as documented by confocal microscopy. The dysfunctional fibroblast growth was validated by scratch test documenting impaired migrational capacity. The results of the cultured dermal fibroblasts were applied to skin biopsies of renal transplant recipients. Skin biopsies of patients treated with MPA expressed less tubulin and actin as compared to control biopsies which could explain potential wound healing problems post transplantation. The perspective of MPA-induced cytoskeletal dysfunction may go beyond wound healing disturbances and has potential beneficial effects on (renal) allografts with respect to scarring. Keywords: Timecourse and MPA and/or Guanosin response
Project description:TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients and longitudinal data from renal and liver transplant recipients.