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The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease.
Kidney Int. 2017 06; 91(6):1436-1446.KI

Abstract

Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated β-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.

Authors+Show Affiliations

Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.Nephrology Division, Internal Medicine Department, Universidade Federal do Paraná, Curitiba, Brazil.Internal Medicine Division, Marcelino Champagnat Hospital, Curitiba, Brazil.Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil.Rare Disease Division, SanofiGenzyme, Framingham, Massachusetts, USA.Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil.Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.PreciThera, Montreal, Quebec, Canada.Nephrology Division, Universidade de São Paulo, São Paulo, Brazil; Medicine Master Degree Program, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil. Electronic address: rosa.moyses@uol.com.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28318623

Citation

Graciolli, Fabiana G., et al. "The Complexity of Chronic Kidney Disease-mineral and Bone Disorder Across Stages of Chronic Kidney Disease." Kidney International, vol. 91, no. 6, 2017, pp. 1436-1446.
Graciolli FG, Neves KR, Barreto F, et al. The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease. Kidney Int. 2017;91(6):1436-1446.
Graciolli, F. G., Neves, K. R., Barreto, F., Barreto, D. V., Dos Reis, L. M., Canziani, M. E., Sabbagh, Y., Carvalho, A. B., Jorgetti, V., Elias, R. M., Schiavi, S., & Moysés, R. M. A. (2017). The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease. Kidney International, 91(6), 1436-1446. https://doi.org/10.1016/j.kint.2016.12.029
Graciolli FG, et al. The Complexity of Chronic Kidney Disease-mineral and Bone Disorder Across Stages of Chronic Kidney Disease. Kidney Int. 2017;91(6):1436-1446. PubMed PMID: 28318623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease. AU - Graciolli,Fabiana G, AU - Neves,Katia R, AU - Barreto,Fellype, AU - Barreto,Daniela V, AU - Dos Reis,Luciene M, AU - Canziani,Maria E, AU - Sabbagh,Yves, AU - Carvalho,Aluizio B, AU - Jorgetti,Vanda, AU - Elias,Rosilene M, AU - Schiavi,Susan, AU - Moysés,Rosa M A, Y1 - 2017/03/18/ PY - 2015/11/18/received PY - 2016/12/19/revised PY - 2016/12/22/accepted PY - 2017/3/21/pubmed PY - 2018/3/23/medline PY - 2017/3/21/entrez KW - FGF23 KW - bone KW - chronic kidney disease KW - hemodialysis KW - hyperparathyroidism KW - mineral metabolism SP - 1436 EP - 1446 JF - Kidney international JO - Kidney Int VL - 91 IS - 6 N2 - Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated β-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/28318623/The_complexity_of_chronic_kidney_disease_mineral_and_bone_disorder_across_stages_of_chronic_kidney_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(17)30025-X DB - PRIME DP - Unbound Medicine ER -