期刊论文详细信息
BMC Nephrology
Mineral bone disorder in chronic kidney disease: head-to-head comparison of the 5/6 nephrectomy and adenine models
Rosa MA Moysés2  Vanda Jorgetti2  Jutta Passlick-Deetjen1  Fabiana G Graciolli2  Elizabeth C Oliveira2  Wagner V Dominguez2  Luciene M dos Reis2  Katia R Neves2  Raquel T Cavallari2  Juliana C Ferreira2  Guaraciaba O Ferrari2 
[1] Division of Nephrology, University of Dusseldorf, Dusseldorf, Germany;Nephrology Department, Universidade de São Paulo, Rua Iperoig, 690, apto 121, São Paulo, Brazil
关键词: Vascular calcification;    Phosphate binder;    Hyperparathyroidism;    Chronic kidney disease;    Bone disease;   
Others  :  1082693
DOI  :  10.1186/1471-2369-15-69
 received in 2013-12-10, accepted in 2014-04-30,  发布年份 2014
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【 摘 要 】

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.

【 授权许可】

   
2014 Ferrari et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Kidney Disease: Improving global outcomes (KDIGO) CKD-MBD work group KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009, 113:S1-S130.
  • [2]Chauntin A, Ferris EB: Experimental renal insufficiency produced by partial nephrectomy. Arch Intern Med 1932, 49:767-787.
  • [3]Shobeiri N, Adams MA, Holden RM: Vascular calcification in animal models of CKD: a review. Am J Nephrol 2010, 31:471-481.
  • [4]Yokozawa T, Oura T, Okada T: Metabolic effects of dietary purine in rats. J Nutr Sci Vitaminol 1982, 28:519-526.
  • [5]Katsumata K, Kusano K, Hirata M, Tsunemi K, Nagano N, Burke SK, Fukushima N: Sevelamer hydrochloride prevents ectopic calcification and renal osteodystrophy in chronic renal failure rats. Kidney Int 2003, 64:441-450.
  • [6]Tamagaki K, Yuan Q, Ohkawa H, Imazeki I, Moriguchi Y, Imai N, Sasaki S, Takeda K, Fukagawa M: Severe Hyperparathyroidism with bone abnormalities and metastatic calcifications in rats with adenine-induced uraemia. Nephrol Dial Transplant 2006, 21:651-659.
  • [7]Nagano N, Myata S, Abe M, Kobayashi N, Wakita S, Yamashita T, Wada M: Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Kidney Int 2006, 69:531-537.
  • [8]Gouveia CH, Jorgetti V, Bianco AC: Effects of thyroid hormone administration and estrogen deficiency on bone mass of female rats. J Bone Miner Res 1997, 12:2098-2107.
  • [9]Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G: Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006, 69:1945-1953.
  • [10]Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Maluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM: Standardized symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2013, 28:2-17.
  • [11]Gagnon RF, Duguid WP: A reproducible model for chronic renal failure in the mouse. Urol Res 1983, 11:11-14.
  • [12]Terai K, Mizukami K, Okada M: Comparison of chronic renal failure rats and modification of the preparation protocol as a hyperphosphataemia model. Nephrology 2008, 13:139-146.
  • [13]Oste L, Behets G, Dams G, Bervoets AR, Marynissen RL, Geryl H, van Hoof VO, de Broe ME, D’Haese PC: Role of dietary phosphorus and degree of uremia in the development of renal bone disease in rats. Ren Fail 2007, 29:1-12.
  • [14]Nagano N, Myiata S, Obana S, Kobayashi N, Abe M, Fukushima N, Wada M: Sevelamer hydrochloride, a calcium free phosphate binder, inhibits parathyroid cell proliferation in partially nephrectomized rats. Nephrol Dial Transplant 2003, 18(3):81-85.
  • [15]Jokihaara J, Porsti IH, Koobi P, Jolma PM, Mustonem JT, Saha HH, Sievanen H, Kannus P, Iwaniec UT, Turner RT, Jarvinen TL: Treatment of experimental renal osteodystrophy with pamidronate. Kidney Int 2008, 74:319-327.
  • [16]Graciolli FG, Neves KR, dos Reis LM, Graciolli RG, Noronha IL, Moysés RM, Jorgetti V: Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia. Nephrol Dial Transplant 2009, 24(5):1416-1421.
  • [17]Damment S, Secker R, Shen V, Lorenzo V, Rodriguez M: Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure. Nephrol Dial Transplant 2011, 26:1803-1812.
  • [18]Neven E, Dams G, Postnov A, Postnov A, Chen B, de Clerck N, de Bro ME, D’Haese PC, Persy V: Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats. Nephrol Diet Transplant 2009, 14:1-10.
  • [19]Moe S, Chen N, Seifert MF, Sinders RM, Duan D, Chen X, Liang Y, Radcliff JS, White KE, Gattone VH 2nd: A rat model of chronic kidney disease-mineral bone disorder. Kidney Int 2009, 75:176-184.
  • [20]Ali BH, Ziada A, Al Husseni I, Beegam S, Nemmar A: Motor and behavioral changes in rats with adenine-induced chronic renal failure: influence of acacia gum treatment. Exp Biol Med 2011, 236(1):107-112.
  • [21]Okabe C, Borges RL, de Almeida DC, Fanelli C, Barlette GP, Machado FG, Arias SC, Malheiros DM, Camara NO, Zatz R, Fujihara CK: NF-κB activation mediates crystal translocation and interstitial inflammation in adenine overload nephropathy. Am J Physiol Renal Physiol 2013, 15(305(2)):F155-F163.
  • [22]Sabbagh Y, Graciolli FG, O’Brien S, Tang W, dos Reis LM, Ryan S, Phillips L, Boulanger J, Song W, Bracken C, Liu S, Ledbetter S, Dechow P, Canziani ME, Carvalho AB, Jorgetti V, Moyses RM, Schiavi SC: Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 2012, 27(8):1757-1772.
  • [23]Stubbs JR, He N, Idiculla A, Gilihan R, Liu S, David V, Hong Y, Quarles LD: Longitudinal evaluation of FGF23 changes and mineral metabolism abnormalities in a mouse model of chronic kidney disease. J Bone Miner Res 2012, 27(1):38-46.
  • [24]Orris I, Burnstock G, Arnett T: Purinergic signaling and bone remodeling. Curr Opin Pharmacol 2010, 10(3):322-330.
  • [25]Cozzolino M, Staniforth M, Liapis H, Finch J, Burke SK, Dusso AS, Slatopolsky E: Sevelamer Hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia. Kidney Int 2003, 64:1653-1661.
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