title: Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.
abstract: Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown.
  
  
  
  In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin-angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs). All participants had an eGFR >45 ml/min, duration of diabetes >20 years and no history of CVD. Serum soluble Klotho levels were measured by a validated immunoassay.
  
  
  
  Participants with microalbuminuria had significantly lower levels of serum Klotho compared with those without microalbuminuria (median [interquartile range], 659.3 [525.3, 827.6] vs 787.7 [629.5, 1007]; p = 0.023). This difference persisted after adjustment for variables including age and eGFR. In a subgroup of 30 individuals with and without microalbuminuria, other markers of phosphate balance were not significantly different.
  
  
  
  In individuals with type 1 diabetes, microalbuminuria is associated with soluble Klotho deficiency. Further studies are required to determine whether soluble Klotho is causally related to the development of cardio-renal disease in type 1 diabetes.
authors.affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK. giuseppe.maltese@kcl.ac.uk.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maltese
authors.affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Fountoulakis
authors.affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Siow
authors.affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
authors.affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Janaka
authors.initials: J
authors.lastname: Karalliedde
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000419:Albuminuria / Q000097:blood* / Q000503:physiopathology / Q000517:prevention & control; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Microalbuminuria; Soluble Klotho; Type 1 diabetes