The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease.
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.
Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Fabiana G
FG
Graciolli
Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Katia R
KR
Neves
Nephrology Division, Internal Medicine Department, Universidade Federal do Paraná, Curitiba, Brazil.
Fellype
F
Barreto
Internal Medicine Division, Marcelino Champagnat Hospital, Curitiba, Brazil.
Daniela V
DV
Barreto
Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Luciene M
LM
Dos Reis
Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil.
Maria E
ME
Canziani
Rare Disease Division, SanofiGenzyme, Framingham, Massachusetts, USA.
Yves
Y
Sabbagh
Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil.
Aluizio B
AB
Carvalho
Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Vanda
V
Jorgetti
Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Rosilene M
RM
Elias
PreciThera, Montreal, Quebec, Canada.
Susan
S
Schiavi
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.
Rosa M A
RMA
Moysés
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010766:Phosphorylation; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D012720:Severity of Illness Index; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C495270:CTNNB1 protein, human; C000717427:FGF23 protein, human; D005819:Genetic Markers; D053244:Osteoprotegerin; C470125:PTH protein, human; C473449:PTH1R protein, human; D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; C422903:SOST protein, human; C506030:TNFRSF11B protein, human; D051176:beta Catenin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium
FGF23; bone; chronic kidney disease; hemodialysis; hyperparathyroidism; mineral metabolism