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

Abstract

BackgroundExperimental 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.MethodsWistar 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.ResultsAt 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.ConclusionsOvert 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.

Fragility fractures and bone remodeling in type 2 diabetes mellitus

“…Особенно значимым влияние этого осложнения СД2 на кость становится при развитии хронической по-чечной недостаточности (ХПН) [42]. ХПН в сочетании со специфическими нарушениями в костной системе приводит к увеличению риска переломов шейки бедра [43].…”

Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease

“…Adenine – induced CKD is a well – tested animal model [8-11], and has been used to investigate the effectiveness of several agents against experimental CKD [12, 13]. …”

A Novel Model of Chronic Kidney Disease in Rats: Dietary Adenine in Combination with Unilateral Nephrectomy

“…Decreases in body weight are known to occur upon pair feeding [6] or oral gavage administration [15] of adenine. In this study, UNx had no immediate impact on weight gain since the body weights of the AD-1K and AD-2K animals were similar during the first 17 days of AD feeding.…”

“…Upon removal of adenine at 0.75% in the diet (AD) after 2 weeks of exposure, some of the effects are reversed and animals partly recover [4]. Longer exposure of rats to AD results in severe, irreversible kidney damage with high mortality, which makes this study protocol unsuitable as a model for testing novel therapeutic agents [4-6]. Some researchers tried to circumvent the limited longer-term tolerability of AD by exposing the rats to lower adenine concentrations (0.25%) for up to 16 weeks [7, 8].…”