title: Association between pharmacodynamic biomarkers and clinical events in the early phase after kidney transplantation: a single-center pilot study.
abstract: BACKGROUND
  Strategies based on monitoring pharmacodynamic effects are increasingly evaluated to individualize immunosuppressive therapy. In the present investigation, both drug-specific and general pharmacodynamic biomarkers were assessed and their association with clinical events early after kidney transplantation was examined.
  
  
  METHODS
  Thirty-five de novo kidney transplant patients receiving basiliximab, enteric-coated mycophenolate sodium (2×720 mg/day), steroids, and tacrolimus (target: 6-8 μg/L) were included. Blood was drawn on days 7(±1) and 21(±2) after transplantation. Mononuclear leucocytes were isolated and the following parameters were investigated: inosine monophosphate dehydrogenase activity (high-performance liquid chromatography-diode array detection), cell proliferation (bromodeoxyuridine test), and CD marker cell surface expression (CD25, CD71, CD26) on stimulated (phytohemagglutinin 2.5 μg/10(6) cells) and nonstimulated CD3 cells. Acute rejection, gastrointestinal adverse effects, leucopenia, and infections were monitored over 3 months.
  
  
  RESULTS
  There was no association between clinical events and inosine monophosphate dehydrogenase activity apart from patients with diarrhea showing a significantly higher inosine monophosphate dehydrogenase activity 2 hours after the enteric-coated mycophenolate sodium dose (P<0.05). Cell proliferation was significantly reduced in patients with leucopenia (P<0.05). CD71 expression was less inducible in patients with infections (P<0.05). A lower CD26 expression on non stimulated CD3 cells predicted freedom from rejection (Day 7; negative predictive value 100%). No associations were found between CD25 expression and events.
  
  
  CONCLUSIONS
  A potential benefit of pharmacodynamic monitoring to optimize immunosuppressive combination therapy has been demonstrated. In particular, CD26 and CD71 may be promising biomarkers to assess adequate immunosuppression in the early phase after kidney transplantation. The results of this pilot study require verification in further trials with more patients and events as well as with different graft types.
authors.affiliation: Zentralinstitut für Klinische Chemie und Laboratoriumsmedizin, Klinikum Stuttgart, Germany. e.wieland@klinikum-stuttgart.de
authors.forename: Eberhard
authors.initials: E
authors.lastname: Wieland
authors.forename: Maria
authors.initials: M
authors.lastname: Shipkova
authors.forename: Yanina
authors.initials: Y
authors.lastname: Martius
authors.forename: Georg
authors.initials: G
authors.lastname: Hasche
authors.forename: Corinne
authors.initials: C
authors.lastname: Klett
authors.forename: Renate
authors.initials: R
authors.lastname: Bolley
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Olbricht
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human