title: Chronic kidney disease induced by adenine: a suitable model of growth retardation in uremia.
abstract: Growth retardation is a major manifestation of chronic kidney disease (CKD) in pediatric patients. The involvement of the various pathogenic factors is difficult to evaluate in clinical studies. Here, we present an experimental model of adenine-induced CKD for the study of growth failure. Three groups (n = 10) of weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD), and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen, creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous front advance as an index of longitudinal growth rate, growth plate histomorphometry, chondrocyte proliferative activity, bone structure, aorta calcifications, and kidney histology were analyzed. Results are means ± SE. AD rats developed renal failure (serum urea nitrogen: 70 ± 6 mg/dl and creatinine: 0.6 ± 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 ± 31 pg/ml). Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 ± 4.8 g, control rats: 112.6 ± 4.7 g, and PF rats: 60.0 ± 3.8 g) and length (AD rats: 7.2 ± 0.2 cm, control rats: 11.1 ± 0.3 cm, and PF rats: 8.1 ± 0.3 cm) gains as well as lower osseous front advances (AD rats: 141 ± 13 μm/day, control rats: 293 ± 16 μm/day, and PF rats: 251 ± 10 μm/day). The processes of chondrocyte maturation and proliferation were impaired in AD rats, as shown by lower growth plate terminal chondrocyte height (21.7 ± 2.3 vs. 26.2 ± 1.9 and 23.9 ± 1.3 μm in control and PF rats) and proliferative activity index (AD rats: 30 ± 2%, control rats: 38 ± 2%, and PF rats: 42 ± 3%). The bone primary spongiosa structure of AD rats was markedly disorganized. In conclusion, adenine-induced CKD in young rats is associated with growth retardation and disturbed endochondral ossification. This animal protocol may be a useful new experimental model to study growth in CKD.
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and.
authors.forename: Débora
authors.initials: D
authors.lastname: Claramunt
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Gil-Peña
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and.
authors.forename: Rocío
authors.initials: R
authors.lastname: Fuente
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: García-López
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Loredo
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and.
authors.forename: Olaya
authors.initials: O
authors.lastname: Hernández-Frías
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and.
authors.forename: Flor A
authors.initials: FA
authors.lastname: Ordoñez
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Rodríguez-Suárez
authors.affiliation: Universidad de Oviedo, Asturias, Spain; and Hospital Universitario Central de Asturias, Oviedo, Spain fsantos@uniovi.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos
mesh_terms: D000225:Adenine; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006128:Growth; D006130:Growth Disorders / Q000209:etiology* / Q000503:physiopathology; D006132:Growth Plate / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D009752:Nutritional Status; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology
chemical_list: D000225:Adenine
keywords: adenine; animal model; chronic kidney disease; growth impairment; growth plate