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. 2020 Feb;35(2):333-342.
doi: 10.1002/jbmr.3894. Epub 2019 Nov 15.

Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease-Mineral Bone Disorder

Colby J Vorland  1 , Annabel Biruete  2 , Pamela J Lachcik  1 , Shruthi Srinivasan  2 , Neal X Chen  2 , Sharon M Moe  2   3   4 , Kathleen M Hill Gallant  1   2
Affiliations

Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease-Mineral Bone Disorder

Colby J Vorland et al. J Bone Miner Res. 2020 Feb.

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 33 P 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 1,25OH2 D, 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 1,25OH2 D 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. © 2019 American Society for Bone and Mineral Research.

Keywords: ANIMAL MODELS; DISORDERS OF CALCIUM/PHOSPHATE METABOLISM; GENETIC ANIMAL MODELS; NUTRITION; PTH/VIT D/FGF23.

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Figures

Figure 1.
Figure 1.
Percent jejunal phosphorus absorption efficiency by age (20- or 30-weeks) and disease (CKD or NL) with sodium-containing and sodium-free absorption buffers. Phosphorus absorption efficiency was calculated as 1-(33P activity remaining in jejunal loop)/(Total 33P activity in dose) after 30 minutes post 33P injection into the jejunal loop. Means and standard error bars are shown for each group. For rats given the sodium-containing absorption buffer (left), there was a main effect for age where 20-week-old rats had higher absorption efficiency compared to both 30-week-olds, and CKD rats had higher absorption efficiency compared to NL, with no significant age x disease interaction. For the sodium-free absorption buffer (right), there was a significant age x disease interaction, where 30-week NL rats had a lower absorption efficiency vs 20-week NL and 20-week CKD rats. Sodium-containing buffer: CKD rats are shown with black bars and white dots, NL rats are shown with white bars and black dots. Sodium-free buffer: CKD rats are shown with black bars with white hashes and white dots, NL rats are shown with white bars with black hashes and black dots. ANOVA p-values for the overall model (PModel), main effect of age (PAge), main effect of disease (PDisease), and interaction of age and disease (PAxD) are shown. n=24 NL, n=24 CKD for sodium-containing buffer; n=24 NL, n=23 CKD for sodium-free buffer, * p < 0.05, ** p < 0.01, *** p < 0.0001.
Figure 2.
Figure 2.
Jejunal phosphorus absorption in plasma over 30 minutes by age (20- or 30-weeks) and disease (CKD or NL) with a sodium-containing absorption buffer (left) or sodium-free buffer (right). Phosphorus absorption from plasma was calculated as the area under the curve of the % of initial dose of 33P of each timepoint over the 30 minute test. Means and standard error bars are shown for each group. For rats given either the sodium-containing or sodium-free absorption buffer, there was a main effect for age where 20-week-old rats had higher absorption efficiency compared to both 30-week-olds, and CKD rats had higher balance compared to NL, with no significant age x disease interaction. Absorption with sodium-containing buffer (left): CKD rats are shown with black lines and black triangles, NL rats are shown with dashed lines and white squares. Absorption with sodium-free buffer: CKD rats are shown with black lines with black triangles, NL rats are shown with dashed lines with black dashes and white squares. ANOVA p-values for the overall model (PModel), main effect of age (PAge), main effect of disease (PDisease), and interaction of age and disease (PAxD) are shown. n=24 NL, n=24 CKD for sodium-containing buffer; n=24 NL, n=23 CKD for sodium-free buffer, ** p < 0.01, *** p < 0.0001.
Figure 3.
Figure 3.
A) Phosphorus balance by age (20- or 30-weeks) and disease (CKD or NL). There was a main effect for age where 20-week-old rats had a more positive phosphorus balance compared to both 30-week-olds, and CKD rats tended to have a more negative balance compared to NL, with no significant age x disease interaction. B) Calcium balance by age and disease. There was a main effect for age where 20-week-old rats had a more positive calcium balance compared to 30-week-olds, but there was no significant effect of disease and no significant age x disease interaction. Balance for each mineral was calculated as intake − fecal + urine. Means and standard error bars are shown for each group. The CKD group is shown in black bars and white circles, and NL white bars with black circles. ANOVA p-values for the overall model (PModel), main effect of age (PAge), main effect of disease (PDisease), and interaction of age and disease (PAxD) are shown. n=49 NL and n=47 CKD for both phosphorus and calcium, * p < 0.05, ** p < 0.01, *** p < 0.0001.
Figure 4.
Figure 4.
A) Percent net phosphorus absorption by age (20- or 30-weeks) and disease (CKD or NL). There was a main effect for age where 20-week-old rats had higher phosphorus absorption compared to 30-week-olds, and a main effect of disease, where CKD rats had higher phosphorus absorption, while no significant age x disease interaction. B) Percent net calcium absorption by age and disease. There was a main effect for age where 20-week-old rats had higher calcium balance compared to 30-week-olds, with no difference by disease and no significant age x disease interaction. Percent net absorption for each mineral was calculated as (intake - fecal)/intake. Means and standard error bars are shown for each group. The CKD group is shown in black bars and white circles, and NL white bars with black circles. ANOVA p-values for the overall model (PModel), main effect of age (PAge), main effect of disease (PDisease), and interaction of age and disease (PAxD) are shown. n=49 NL and n=47 CKD for both phosphorus and calcium, * p < 0.05, ** p < 0.01.
Figure 5.
Figure 5.
RNA expression of NaPi-2b, PiT-1 in jejunum and duodenum, and NaPi-2a and NaPi- 2c in kidney. A) NaPi-2b mRNA was not different between groups in the jejunum. B) PiT-1 mRNA was not different between groups in the jejunum. C) NaPi-2b mRNA was lower in CKD rats vs NL in the duodenum. D) PiT-1 mRNA was not different between groups in the duodenum. E) NaPi-2a was lower in CKD rats vs NL in the kidney. F) NaPi-2c was lower in CKD rats vs NL in the kidney. Outliers are excluded above 2 SD of the mean. The CKD group is shown in black bars and white circles, and NL white bars with black circles. ANOVA p-values for the overall model (PModel), main effect of age (PAge), main effect of disease (PDisease), and interaction of age and disease (PAxD) are shown. n=46 NL and n=44 CKD for jejunum NaPi-2b and PiT-1, n=48 NL and n=46 CKD for duodenum NaPi-2b and PiT-1, n=41 NL and n=44 CKD for kidney NaPi-2a, n=42 NL and n=44 CKD for kidney NaPi-2c, * p < 0.05, ** p < 0.01, *** p < 0.0001.
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References

    1. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69(11):1945–53. - PubMed
    1. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71(1):31–8. - PubMed
    1. Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79(12):1370–8. - PMC - PubMed
    1. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382(9889):339–52. - PubMed
    1. Miller PD. Chronic kidney disease and the skeleton. Bone Res. 2014;2:14044. - PMC - PubMed

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