Email updates

Keep up to date with the latest news and content from BMC Nephrology and BioMed Central.

Open Access Research article

Mineral bone disorder in chronic kidney disease: head-to-head comparison of the 5/6 nephrectomy and adenine models

Guaraciaba O Ferrari1, Juliana C Ferreira1, Raquel T Cavallari1, Katia R Neves1, Luciene M dos Reis1, Wagner V Dominguez1, Elizabeth C Oliveira1, Fabiana G Graciolli1, Jutta Passlick-Deetjen2, Vanda Jorgetti1 and Rosa MA Moysés1*

Author Affiliations

1 Nephrology Department, Universidade de São Paulo, Rua Iperoig, 690, apto 121, São Paulo, Brazil

2 Division of Nephrology, University of Dusseldorf, Dusseldorf, Germany

For all author emails, please log on.

BMC Nephrology 2014, 15:69  doi:10.1186/1471-2369-15-69

Published: 3 May 2014

Abstract

Background

Experimental models are important to the understanding of the pathophysiology of, as well as the effects of therapy on, certain diseases. In the case of chronic kidney disease-mineral bone disorder, there are currently two models that are used in evaluating the disease: 5/6 nephrectomy (Nx) and adenine-induced renal failure (AIRF). However, the two models have never been compared in studies using animals maintained under similar conditions. Therefore, we compared these two models, focusing on the biochemical, bone histomorphometry, and vascular calcification aspects.

Methods

Wistar rats, initially fed identical diets, were divided into two groups: those undergoing 5/6 Nx (5/6Nx group) and those that were switched to an adenine-enriched diet (AIRF group). After 9 weeks, animals were sacrificed, and we conducted biochemical and bone histomorphometry analyses, as well as assessing vascular calcification.

Results

At sacrifice, the mean body weight was higher in the 5/6Nx group than in the AIRF group, as was the mean blood pressure. No differences were seen regarding serum phosphate, ionized calcium, intact parathyroid hormone (PTH), or fibroblast growth factor 23 (FGF23). However, creatinine clearance was lower and fractional excretion of phosphate (FeP) was higher in the AIRF group rats, which also had a more severe form of high-turnover bone disease. Vascular calcification, as evaluated through von Kossa staining, was not observed in any of the animals.

Conclusions

Overt vascular calcification was not seen in either model as applied in this study. Under similar conditions of diet and housing, the AIRF model produces a more severe form of bone disease than does 5/6 Nx. This should be taken into account when the choice is made between these models for use in preclinical studies.

Keywords:
Bone disease; Chronic kidney disease; Hyperparathyroidism; Phosphate binder; Vascular calcification