Abstract
The Cy/+ rat has been characterized as a progressive model of chronic kidney disease–mineral bone disorder (CKD-MBD). We aimed to determine the effect of kidney disease progression on intestinal phosphorus absorption and whole-body phosphorus balance in this model. A total of 48 Cy/+ (CKD) and 48 normal littermates (NL) rats were studied at two ages: 20 weeks and 30 weeks, to model progressive kidney function decline at approximately 50% and 20% of normal kidney function. Sodium-dependent and sodium-independent intestinal phosphorus absorption efficiency were measured by the in situ jejunal ligated loop method using 33P radioisotope. Our results show that CKD rats had slightly higher sodium-dependent phosphorus absorption compared to NL rats, and absorption decreased from 20 to 30 weeks. These results are in contrast to plasma 1,25OH 2D, which was lower in CKD rats. Gene expression of the major intestinal phosphorus transporter, NaPi-2b, was not different between CKD and NL rats in the jejunum but was lower in CKD rats versus NL rats in the duodenum. Jejunal ligated loop phosphorus absorption results are consistent with percent net phosphorus absorption results obtained from metabolic balance: higher net percent phosphorus absorption values in CKD rats compared with NL, and lower values in 30-week-olds compared with 20-week-olds. Phosphorus balance was negative (below zero) in CKD rats, significantly lower in 30-week-old rats compared with 20-week-old rats, and lower in CKD rats compared with NL rats at both ages. These results demonstrate no reduction in intestinal phosphorus absorption with progression of CKD despite lower 1,25OH 2D status when assessed by an in situ ligated loop test, which is in contrast to the majority of in vitro studies, and if confirmed in further studies, could challenge the physiological relevance of in vitro findings.
Original language | English (US) |
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Pages (from-to) | 333-342 |
Number of pages | 10 |
Journal | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research |
Volume | 35 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2020 |
Bibliographical note
Funding Information:AB reports personal fees from Amgen; and grants from Keryx, outside the submitted work. SMM reports grants from Chugai and grants from Keryx, during the conduct of the study; and personal fees from Amgen outside the submitted work. KMHG reports grants from NIH NIDDK K01 DK102864, and grants from USDA NIFA 1008923, during the conduct of the study; personal fees from Relypsa, Inc, grants from Chugai Pharmaceutical Co., Ltd, and personal fees from Tricida, Inc, outside the submitted work. CJV, PJL, SS, and NXC have nothing to disclose.
Funding Information:
This work was supported through NIH K01 DK102864 (to KMHG), the Ralph W. and Grace M. Showalter Research Trust Fund (to KMHG), and a USDA NIFA Hatch Project (grant #1008923, to KMHG). SMM was supported by NIH R01 DK11087103 and a Veterans Affairs Merit Award (BX001471). AB was supported by NIH T32 (AR065971‐04). We thank Dr. James Fleet for his scientific and technical guidance, and Courtney Nelson and Rebecca Lapides for their technical assistance. Author's roles: Study design: KMHG, SMM, and CJV; Study conduct: CJV, PJL, and KMHG; Data collection: CJV, AB, PJL, SS, and NXC; Data analysis: CJV and KMHG; Data interpretation: CJV and KMHG; Drafting manuscript: CJV and KMHG; Revising manuscript content: CJV, AB, NXC, SMM, and KMHG; Approving final version of manuscript: all authors. CJV and KMHG take responsibility for the integrity of the data analysis. Data Sharing : The data and diet datasheet that support the findings of this study are openly available in OSF at https://doi.org/10.17605/OSF.IO/BUECQ .
Publisher Copyright:
© 2019 American Society for Bone and Mineral Research
Keywords
- ANIMAL MODELS
- DISORDERS OF CALCIUM/PHOSPHATE METABOLISM
- GENETIC ANIMAL MODELS
- NUTRITION
- PTH/VIT D/FGF23
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.