title: Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation.
abstract: OBJECTIVE
  Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9-12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys.
  
  
  METHODS
  Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass-spectrometry.
  
  
  RESULTS
  The SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40 mmol/mol) and 8.6% (70 mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients.
  
  
  CONCLUSIONS
  Patients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: t.m.reine@medisin.uio.no.
authors.forename: Trine Marita
authors.initials: TM
authors.lastname: Reine
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Ingrid Benedicte Moss
authors.initials: IB
authors.lastname: Kolseth
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Astri Jeanette
authors.initials: AJ
authors.lastname: Meen
authors.affiliation: Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Jørn Petter
authors.initials: JP
authors.lastname: Lindahl
authors.affiliation: Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Health Science, University of Tromsø, Tromsø, Norway.
authors.forename: Trond Geir
authors.initials: TG
authors.lastname: Jenssen
authors.affiliation: Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Finn Per
authors.initials: FP
authors.lastname: Reinholt
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston University Medical Campus, Boston, MA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston University Medical Campus, Boston, MA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Svein Olav
authors.initials: SO
authors.lastname: Kolset
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology; D005260:Female; D006497:Heparan Sulfate / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011509:Proteoglycans / Q000097:blood
chemical_list: D006497:Heparan Sulfate; D011509:Proteoglycans
keywords: Diabetes; Heparan sulfate; Hyperglycemia; Kidney; Proteoglycans