title: Rationale for and study design of the sulodexide trials in Type 2 diabetic, hypertensive patients with microalbuminuria or overt nephropathy.
abstract: BACKGROUND
  Patients with Type 2 diabetes and albuminuria are at high risk to progress to end-stage renal disease (ESRD). Although angiotensin receptor blockers confer renoprotection, many diabetic patients still develop overt nephropathy and reach ESRD. Glycosaminoglycans belong to the same family as heparin and heparinoids. Pilot studies with sulodexide, a glycosaminoglycan, have shown that sulodexide can reduce urinary albumin excretion rates in diabetic patients. No hard renal end-point data are available.
  
  
  METHODS
  Two multicentre, double-masked, randomized placebo controlled trials were designed to study the renoprotective potential of sulodexide. The Sulodexide Microalbuminuria Trial examined the efficacy of sulodexide given over 26 weeks in 1000 patients with Type 2 diabetes, hypertension and microalbuminuria. The Sulodexide Overt Nephropathy Trial examined the efficacy of sulodexide in 2240 patients with Type 2 diabetes, hypertension and proteinuria > or = 900 mg/24 h.
  
  
  RESULTS
  The primary outcome of The Sulodexide Microalbuminuria Trial was (i) conversion to normoalbuminuria and at least a 25% decrease in the urinary albumin creatinine ratio (UACR), or (ii) at least a 50% reduction in UACR. The primary outcome of The Sulodexide Overt Nephropathy Trial was time to a composite end point of doubling of serum creatinine or ESRD.
  
  
  CONCLUSIONS
  The sulodexide nephropathy programme will document whether therapy with sulodexide confers renal protection in Type 2 diabetes and nephropathy.
authors.affiliation: Department of Clinical Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. H.J.Lambers.Heerspink@med.umcg.nl
authors.forename: H J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.forename: M J
authors.initials: MJ
authors.lastname: Fowler
authors.forename: J
authors.initials: J
authors.lastname: Volgi
authors.forename: A T
authors.initials: AT
authors.lastname: Reutens
authors.forename: I
authors.initials: I
authors.lastname: Klein
authors.forename: T A
authors.initials: TA
authors.lastname: Herskovits
authors.forename: D K
authors.initials: DK
authors.lastname: Packham
authors.forename: I R
authors.initials: IR
authors.lastname: Fraser
authors.forename: S L
authors.initials: SL
authors.lastname: Schwartz
authors.forename: C
authors.initials: C
authors.lastname: Abaterusso
authors.forename: J
authors.initials: J
authors.lastname: Lewis
mesh_terms: D000419:Albuminuria / Q000139:chemically induced / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications*; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D016896:Treatment Outcome
chemical_list: D006025:Glycosaminoglycans; D007004:Hypoglycemic Agents; C007858:glucuronyl glucosamine glycan sulfate