Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation.

Autor: Reine TM; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: t.m.reine@medisin.uio.no., Kolseth IB; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Meen AJ; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Lindahl JP; Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Jenssen TG; 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., Reinholt FP; Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway., Zaia J; Department of Biochemistry, Boston University School of Medicine, Boston University Medical Campus, Boston, MA, USA., Shao C; Department of Biochemistry, Boston University School of Medicine, Boston University Medical Campus, Boston, MA, USA., Hartmann A; Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Kolset SO; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Jazyk: angličtina
Zdroj: Diabetes research and clinical practice [Diabetes Res Clin Pract] 2015 Jan; Vol. 107 (1), pp. 46-53. Date of Electronic Publication: 2014 Oct 28.
DOI: 10.1016/j.diabres.2014.10.006
Abstrakt: Aims: 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.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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