title: The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood.
abstract: The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.
authors.affiliation: Department of Pediatrics, University of Chieti, Via dei Vestini 5, 66100, Chieti, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Giannini
authors.forename: Ebe
authors.initials: E
authors.lastname: D'Adamo
authors.forename: Tommaso
authors.initials: T
authors.lastname: de Giorgis
authors.forename: Valentina
authors.initials: V
authors.lastname: Chiavaroli
authors.forename: Alberto
authors.initials: A
authors.lastname: Verrotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.forename: Angelika
authors.initials: A
authors.lastname: Mohn
mesh_terms: D002648:Child; D003928:Diabetic Nephropathies / Q000209:etiology*; D005260:Female; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D008297:Male; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D012044:Regression Analysis
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic