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. 2021 Apr;99(4):977-985.
doi: 10.1016/j.kint.2020.07.041. Epub 2020 Sep 11.

Mineral bone disease in autosomal dominant polycystic kidney disease

Berenice Gitomer  1 , Renata Pereira  2 , Isidro B Salusky  2 , Jason W Stoneback  3 , Tamara Isakova  4 , Xuan Cai  4 , Lorien S Dalrymple  5 , Norma Ofsthun  5 , Zhiying You  1 , Harmut H Malluche  6 , Franklin Maddux  7 , Diana George  1 , Vicente Torres  8 , Arlene Chapman  9 , Theodore I Steinman  10 , Myles Wolf  11 , Michel Chonchol  12
Affiliations

Mineral bone disease in autosomal dominant polycystic kidney disease

Berenice Gitomer et al. Kidney Int. 2021 Apr.

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.

Keywords: ADPKD; bone; mineral metabolism.

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Figures

Figure 1
Figure 1. (a) Intact fibroblast growth factor-23 (iFGF23) increase is greater in patients with autosomal dominant polycystic kidney disease (ADPKD).
Unadjusted associations of iFGF23 with estimated glomerular filtration rate (eGFR) decline in the HALT-PKD and Chronic Renal Insufficiency Cohort (CRIC) cohorts. (b) Alkaline phosphatase is lower in patients with ADPKD. Unadjusted associations of alkaline phosphatase with eGFR decline in the HALT-PKD and CRIC cohorts. (c) Intact parathyroid hormone (PTH) in patients with ADPKD and non- ADPKD chronic kidney disease. Unadjusted associations of intact PTH with eGFR decline in the HALT-PKD and CRIC cohorts.
Figure 2
Figure 2. Immunohistochemical trabecular bone expression of fibroblast growth factor 23, dentin matrix acidic phosphoprotein1 (DMP1), and sclerostin in early autosomal dominant polycystic kidney disease (ADPKD).
BM, bone marrow, CB, cortical bone; TB, trabecular bone.
See this image and copyright information in PMC

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