ABSTRACT
This corrects the article DOI: 10.1038/pr.2017.95.
ABSTRACT
BackgroundIn a model of growth retardation secondary to chronic kidney disease (CKD) induced by adenine, this study explores the effects of growth hormone (GH) therapy on growth plate and mineral metabolism.MethodsWeaning female rats receiving a 0.5% adenine diet during 21 days, untreated (AD) or treated with GH (ADGH) for 1 week, were compared with control rats receiving normal diet, either ad libitum or pair-fed with AD animals. AD and ADGH rats had similarly elevated serum concentrations of urea nitrogen, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).ResultsUremia induced by adenine caused growth retardation and disturbed growth cartilage chondrocyte hypertrophy. We demonstrated marked expression of aquaporin 1 in the growth plate, but its immunohistochemical signal and the expression levels of other proteins potentially related with chondrocyte enlargement, such as Na-K-2Cl cotransporter, insulin-like growth factor 1 (IGF-1), and IGF-1 receptor, were not different among the four groups of rats. The distribution pattern of vascular endothelial growth factor was also similar. AD rats developed femur bone structure abnormalities analyzed by micro-computerized tomography.ConclusionGH treatment accelerated longitudinal growth velocity, stimulated the proliferation and enlargement of chondrocytes, and did not modify the elevated serum PTH or FGF23 concentrations or the abnormal bone structure.
Subject(s)
Growth Hormone/pharmacology , Growth Plate/drug effects , Minerals/metabolism , Uremia/metabolism , Adenine , Animals , Blood Urea Nitrogen , Chondrocytes/metabolism , Female , Fibroblast Growth Factors/blood , Inflammation , Parathyroid Hormone/blood , Rats , Rats, Sprague-Dawley , Uremia/chemically induced , Vascular Endothelial Growth Factor A/metabolism , X-Ray MicrotomographyABSTRACT
La enfermedad renal crónica (ERC) tiene características específicas. De manera especial, el retraso del crecimiento es una manifestación clínica importante de la ERC que se inicia en la infancia ya que se presenta en un gran número de lactantes y niños con ERC, y repercute profundamente en la autoestima e integración social de los pacientes afectados. Varios factores asociados con la ERC pueden provocar retraso del crecimiento por interferencia con la fisiología normal de la placa de crecimiento, el órgano donde se produce el ritmo de crecimiento longitudinal. Apenas es posible estudiar la placa de crecimiento en seres humanos y ello justifica el uso de modelos animales. El modelo más utilizado para investigar el retraso del crecimiento en la ERC son ratas jóvenes que se convierten en urémicas por nefrectomía 5/6. Este artículo revisa las características de este modelo y analiza el uso de la ERC inducida por una dieta con elevado contenido de adenina como protocolo de investigación alternativo (AU)
Pediatric chronic kidney disease (CKD) has peculiar features. In particular, growth impairment is a major clinical manifestation of CKD that debuts in pediatric age because it presents in a large proportion of infants and children with CKD and has a profound impact on the self-esteem and social integration of the stunted patients. Several factors associated with CKD may lead to growth retardation by interfering with the normal physiology of growth plate, the organ where longitudinal growth rate takes place. The study of growth plate is hardly possible in humans and justifies the use of animal models. Young rats made uremic by 5/6 nephrectomy have been widely used as a model to investigate growth retardation in CKD. This article examines the characteristics of this model and analyzes the utilization of CKD induced by high adenine diet as an alternative research protocol (AU)
Subject(s)
Animals , Rats , Renal Insufficiency, Chronic/physiopathology , Growth Disorders/physiopathology , Growth Plate/physiopathology , Disease Models, Animal , Adenine/adverse effects , Uremia/chemically induced , NephrectomyABSTRACT
Pediatric chronic kidney disease (CKD) has peculiar features. In particular, growth impairment is a major clinical manifestation of CKD that debuts in pediatric age because it presents in a large proportion of infants and children with CKD and has a profound impact on the self-esteem and social integration of the stunted patients. Several factors associated with CKD may lead to growth retardation by interfering with the normal physiology of growth plate, the organ where longitudinal growth rate takes place. The study of growth plate is hardly possible in humans and justifies the use of animal models. Young rats made uremic by 5/6 nephrectomy have been widely used as a model to investigate growth retardation in CKD. This article examines the characteristics of this model and analyzes the utilization of CKD induced by high adenine diet as an alternative research protocol.
Subject(s)
Adenine/toxicity , Disease Models, Animal , Nephrectomy/adverse effects , Renal Insufficiency, Chronic/etiology , Administration, Oral , Adolescent , Animals , Chemokines/physiology , Child , Child, Preschool , Dwarfism/etiology , Dwarfism/pathology , Dwarfism/physiopathology , Female , Growth Plate/pathology , Humans , Infant , Infant, Newborn , Male , Mesothelin , Nephrectomy/methods , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Rats , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Young AdultABSTRACT
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.
