Mineral bone disease in autosomal dominant polycystic kidney disease

Berenice Gitomer; Renata Pereira; Isidro B. Salusky; Jason W. Stoneback; Tamara Isakova; Xuan Cai; Lorien S. Dalrymple; Norma Ofsthun; Zhiying You; Harmut H. Malluche; Franklin Maddux; Diana George; Vicente Torres; Arlene Chapman; Theodore I. Steinman; Myles Wolf; Michel Chonchol

doi:10.1016/j.kint.2020.07.041

Mineral bone disease in autosomal dominant polycystic kidney disease

Berenice Gitomer
, Renata Pereira
, Isidro B. Salusky
, Jason W. Stoneback
, Tamara Isakova
, Xuan Cai
, Lorien S. Dalrymple
, Norma Ofsthun
, Zhiying You
, Harmut H. Malluche
, Franklin Maddux
, Diana George
, Vicente Torres
, Arlene Chapman
, Theodore I. Steinman
, Myles Wolf
, Michel Chonchol

Internal Medicine

Producción científica: Article › revisión exhaustiva

23 Citas (Scopus)

Resumen

Mice with disruption of Pkd1 in osteoblasts demonstrate reduced bone mineral density, trabecular bone volume and cortical thickness. To date, the bone phenotype in adult patients with autosomal dominant polycystic kidney disease (ADPKD) with stage I and II chronic kidney disease has not been investigated. To examine this, we characterized biochemical markers of mineral metabolism, examined bone turnover and biology, and estimated risk of fracture in patients with ADPKD. Markers of mineral metabolism were measured in 944 patients with ADPKD and other causes of kidney disease. Histomorphometry and immunohistochemistry were compared on bone biopsies from 20 patients with ADPKD with a mean eGFR of 97 ml/min/1.73m² and 17 healthy individuals. Furthermore, adults with end stage kidney disease (ESKD) initiating hemodialysis between 2002-2013 and estimated the risk of bone fracture associated with ADPKD as compared to other etiologies of kidney disease were examined. Intact fibroblast growth factor 23 was higher and total alkaline phosphatase lower in patients with compared to patients without ADPKD with chronic kidney disease. Compared to healthy individuals, patients with ADPKD demonstrated significantly lower osteoid volume/bone volume (0.61 vs. 1.21%) and bone formation rate/bone surface (0.012 vs. 0.026 μm³/μm²/day). ESKD due to ADPKD was not associated with a higher risk of fracture as compared to ESKD due to diabetes (age adjusted incidence rate ratio: 0.53 (95% confidence interval 0.31, 0.74) or compared to other etiologies of kidney disease. Thus, individuals with ADPKD have lower alkaline phosphatase, higher circulating intact fibroblast growth factor 23 and decreased bone formation rate. However, ADPKD is not associated with higher rates of bone fracture in ESKD.

Idioma original	English
Páginas (desde-hasta)	977-985
Número de páginas	9
Publicación	Kidney International
Volumen	99
N.º	4
DOI	https://doi.org/10.1016/j.kint.2020.07.041
Estado	Published - abr 2021

Nota bibliográfica

Publisher Copyright:
© 2020 International Society of Nephrology

Financiación

This study was funded with federal funds from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (R01 DK094796). The authors analyzed and interpreted the data for this manuscript. All aspects of manuscript writing were carried out by the authors. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. This study was funded with federal funds from the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health ( R01 DK094796 ). The authors analyzed and interpreted the data for this manuscript. All aspects of manuscript writing were carried out by the authors. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. MC reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases (during the conduct of the study) as well as from the Department of Defense, Otsuka, Sanofi, and Corvidia (outside the submitted work). All the other authors declared no competing interests.

Financiadores	Número del financiador
Otsuka America
National Institutes of Health (NIH)
U.S. Department of Defense
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK094796
National Institute of Diabetes and Digestive and Kidney Diseases
U.S. Department of Veterans Affairs
Sanofi

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Nephrology

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10.1016/j.kint.2020.07.041

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Gitomer, B., Pereira, R., Salusky, I. B., Stoneback, J. W., Isakova, T., Cai, X., Dalrymple, L. S., Ofsthun, N., You, Z., Malluche, H. H., Maddux, F., George, D., Torres, V., Chapman, A., Steinman, T. I., Wolf, M., & Chonchol, M. (2021). Mineral bone disease in autosomal dominant polycystic kidney disease. Kidney International, 99(4), 977-985. https://doi.org/10.1016/j.kint.2020.07.041

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title = "Mineral bone disease in autosomal dominant polycystic kidney disease",

abstract = "Mice with disruption of Pkd1 in osteoblasts demonstrate reduced bone mineral density, trabecular bone volume and cortical thickness. To date, the bone phenotype in adult patients with autosomal dominant polycystic kidney disease (ADPKD) with stage I and II chronic kidney disease has not been investigated. To examine this, we characterized biochemical markers of mineral metabolism, examined bone turnover and biology, and estimated risk of fracture in patients with ADPKD. Markers of mineral metabolism were measured in 944 patients with ADPKD and other causes of kidney disease. Histomorphometry and immunohistochemistry were compared on bone biopsies from 20 patients with ADPKD with a mean eGFR of 97 ml/min/1.73m2 and 17 healthy individuals. Furthermore, adults with end stage kidney disease (ESKD) initiating hemodialysis between 2002-2013 and estimated the risk of bone fracture associated with ADPKD as compared to other etiologies of kidney disease were examined. Intact fibroblast growth factor 23 was higher and total alkaline phosphatase lower in patients with compared to patients without ADPKD with chronic kidney disease. Compared to healthy individuals, patients with ADPKD demonstrated significantly lower osteoid volume/bone volume (0.61 vs. 1.21\%) and bone formation rate/bone surface (0.012 vs. 0.026 μm3/μm2/day). ESKD due to ADPKD was not associated with a higher risk of fracture as compared to ESKD due to diabetes (age adjusted incidence rate ratio: 0.53 (95\% confidence interval 0.31, 0.74) or compared to other etiologies of kidney disease. Thus, individuals with ADPKD have lower alkaline phosphatase, higher circulating intact fibroblast growth factor 23 and decreased bone formation rate. However, ADPKD is not associated with higher rates of bone fracture in ESKD.",

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author = "Berenice Gitomer and Renata Pereira and Salusky, \{Isidro B.\} and Stoneback, \{Jason W.\} and Tamara Isakova and Xuan Cai and Dalrymple, \{Lorien S.\} and Norma Ofsthun and Zhiying You and Malluche, \{Harmut H.\} and Franklin Maddux and Diana George and Vicente Torres and Arlene Chapman and Steinman, \{Theodore I.\} and Myles Wolf and Michel Chonchol",

note = "Publisher Copyright: {\textcopyright} 2020 International Society of Nephrology",

year = "2021",

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doi = "10.1016/j.kint.2020.07.041",

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Gitomer, B, Pereira, R, Salusky, IB, Stoneback, JW, Isakova, T, Cai, X, Dalrymple, LS, Ofsthun, N, You, Z, Malluche, HH, Maddux, F, George, D, Torres, V, Chapman, A, Steinman, TI, Wolf, M & Chonchol, M 2021, 'Mineral bone disease in autosomal dominant polycystic kidney disease', Kidney International, vol. 99, n.º 4, pp. 977-985. https://doi.org/10.1016/j.kint.2020.07.041

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T1 - Mineral bone disease in autosomal dominant polycystic kidney disease

AU - Gitomer, Berenice

AU - Pereira, Renata

AU - Salusky, Isidro B.

AU - Stoneback, Jason W.

AU - Isakova, Tamara

AU - Cai, Xuan

AU - Dalrymple, Lorien S.

AU - Ofsthun, Norma

AU - You, Zhiying

AU - Malluche, Harmut H.

AU - Maddux, Franklin

AU - George, Diana

AU - Torres, Vicente

AU - Chapman, Arlene

AU - Steinman, Theodore I.

AU - Wolf, Myles

AU - Chonchol, Michel

PY - 2021/4

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N2 - Mice with disruption of Pkd1 in osteoblasts demonstrate reduced bone mineral density, trabecular bone volume and cortical thickness. To date, the bone phenotype in adult patients with autosomal dominant polycystic kidney disease (ADPKD) with stage I and II chronic kidney disease has not been investigated. To examine this, we characterized biochemical markers of mineral metabolism, examined bone turnover and biology, and estimated risk of fracture in patients with ADPKD. Markers of mineral metabolism were measured in 944 patients with ADPKD and other causes of kidney disease. Histomorphometry and immunohistochemistry were compared on bone biopsies from 20 patients with ADPKD with a mean eGFR of 97 ml/min/1.73m2 and 17 healthy individuals. Furthermore, adults with end stage kidney disease (ESKD) initiating hemodialysis between 2002-2013 and estimated the risk of bone fracture associated with ADPKD as compared to other etiologies of kidney disease were examined. Intact fibroblast growth factor 23 was higher and total alkaline phosphatase lower in patients with compared to patients without ADPKD with chronic kidney disease. Compared to healthy individuals, patients with ADPKD demonstrated significantly lower osteoid volume/bone volume (0.61 vs. 1.21%) and bone formation rate/bone surface (0.012 vs. 0.026 μm3/μm2/day). ESKD due to ADPKD was not associated with a higher risk of fracture as compared to ESKD due to diabetes (age adjusted incidence rate ratio: 0.53 (95% confidence interval 0.31, 0.74) or compared to other etiologies of kidney disease. Thus, individuals with ADPKD have lower alkaline phosphatase, higher circulating intact fibroblast growth factor 23 and decreased bone formation rate. However, ADPKD is not associated with higher rates of bone fracture in ESKD.

AB - Mice with disruption of Pkd1 in osteoblasts demonstrate reduced bone mineral density, trabecular bone volume and cortical thickness. To date, the bone phenotype in adult patients with autosomal dominant polycystic kidney disease (ADPKD) with stage I and II chronic kidney disease has not been investigated. To examine this, we characterized biochemical markers of mineral metabolism, examined bone turnover and biology, and estimated risk of fracture in patients with ADPKD. Markers of mineral metabolism were measured in 944 patients with ADPKD and other causes of kidney disease. Histomorphometry and immunohistochemistry were compared on bone biopsies from 20 patients with ADPKD with a mean eGFR of 97 ml/min/1.73m2 and 17 healthy individuals. Furthermore, adults with end stage kidney disease (ESKD) initiating hemodialysis between 2002-2013 and estimated the risk of bone fracture associated with ADPKD as compared to other etiologies of kidney disease were examined. Intact fibroblast growth factor 23 was higher and total alkaline phosphatase lower in patients with compared to patients without ADPKD with chronic kidney disease. Compared to healthy individuals, patients with ADPKD demonstrated significantly lower osteoid volume/bone volume (0.61 vs. 1.21%) and bone formation rate/bone surface (0.012 vs. 0.026 μm3/μm2/day). ESKD due to ADPKD was not associated with a higher risk of fracture as compared to ESKD due to diabetes (age adjusted incidence rate ratio: 0.53 (95% confidence interval 0.31, 0.74) or compared to other etiologies of kidney disease. Thus, individuals with ADPKD have lower alkaline phosphatase, higher circulating intact fibroblast growth factor 23 and decreased bone formation rate. However, ADPKD is not associated with higher rates of bone fracture in ESKD.

KW - ADPKD

KW - bone

KW - mineral metabolism

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Mineral bone disease in autosomal dominant polycystic kidney disease

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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