TY - JOUR
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
N1 - Funding Information:
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.
Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2020 International Society of Nephrology
PY - 2021/4
Y1 - 2021/4
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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UR - http://www.scopus.com/inward/citedby.url?scp=85101306022&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2020.07.041
DO - 10.1016/j.kint.2020.07.041
M3 - Article
C2 - 32926884
AN - SCOPUS:85101306022
SN - 0085-2538
VL - 99
SP - 977
EP - 985
JO - Kidney International
JF - Kidney International
IS - 4
ER -
