title: Simultaneous pancreas-kidney transplantation in patients with type 1 diabetes reverses elevated MBL levels in association with MBL2 genotype and VEGF expression.
abstract: OBJECTIVE
  High levels of circulating mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy and hyperglycaemia-induced vasculopathy. Here, we aimed to assess the effect of glycaemic control on circulating levels of MBL and the relationship of these levels with vascular damage.
  
  
  METHODS
  We assessed MBL levels and corresponding MBL2 genotype, together with vascular endothelial growth factor (VEGF) levels as a marker of vascular damage, in type 1 diabetes patients with diabetic nephropathy before and after simultaneous pancreas-kidney (SPK) transplantation. We included diabetic nephropathy patients (n = 21), SPK patients (n = 37), healthy controls (n = 19), type 1 diabetes patients (n = 15) and diabetic nephropathy patients receiving only a kidney transplant (n = 15). Fourteen diabetic nephropathy patients were followed up for 12 months after SPK.
  
  
  RESULTS
  We found elevated circulating MBL levels in diabetic nephropathy patients, and a trend towards elevated circulating MBL levels in type 1 diabetes patients, compared with healthy control individuals. MBL levels in SPK patients completely normalised and our data indicate that this predominantly occurs in patients with a polymorphism in the MBL2 gene. By contrast, MBL levels in kidney transplant only patients remained elevated, suggesting that glycaemic control but not reversal of renal failure is associated with decreased MBL levels. In line, levels of glucose and HbA1c, but not creatinine levels and estimated GFR, were correlated with MBL levels. VEGF levels were associated with levels of MBL and HbA1c in an MBL-polymorphism-dependent manner.
  
  
  CONCLUSIONS
  Taken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands. r.bijkerk@lumc.nl.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. r.bijkerk@lumc.nl.
authors.forename: Roel
authors.identifier: http://orcid.org/0000-0002-6438-4133
authors.initials: R
authors.lastname: Bijkerk
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Pol
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Meriem
authors.initials: M
authors.lastname: Khairoun
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: van Gijlswijk-Jansen
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Lievers
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Aiko P J
authors.initials: AP
authors.lastname: de Vries
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Eelco J
authors.initials: EJ
authors.lastname: de Koning
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Hans W
authors.initials: HW
authors.lastname: de Fijter
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Rolf H A M
authors.initials: RH
authors.lastname: Vossen
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
mesh_terms: D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000601:surgery*; D005260:Female; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics; D016035:Pancreas Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D042461:Vascular Endothelial Growth Factor A
keywords: Diabetic nephropathy; MBL; Mannan-binding lectin; Simultaneous pancreas–kidney transplantation; Type 1 diabetes; VEGF; Vascular injury