Mineral bone disease in autosomal dominant polycystic kidney disease.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • April 2021

Published In

Volume / Issue

  • 99 / 4

Start / End Page

  • 977 - 985

PubMed ID

  • 32926884

Pubmed Central ID

  • PMC7993988

Electronic International Standard Serial Number (EISSN)

  • 1523-1755

Digital Object Identifier (DOI)

  • 10.1016/j.kint.2020.07.041

Language

  • eng

Conference Location

  • United States