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

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. Sodiumdependent 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 1,25OH 2 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 1,25OH 2 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.Baseline blood biochemistries at 16 weeks of age in groups randomized to 20-week-old and 30-week-old groups. ANOVA p values for the main effect of disease (P Disease ) are shown, and means AE SE are shown for each group. Bold p values are significant, p < 0.05. Plasma creatinine was higher in CKD versus NL. Plasma PTH did not differ between groups. iFGF23 was higher in CKD rats versus NL. Plasma 1,25D was lower in CKD versus NL.Journal of Bone and Mineral Research n 336 VORLAND ET AL.35. Lee D, Walling MW, Corry DB. Phosphate transport across rat jejunum: influence of sodium, pH, and 1, 25-dihydroxyvitamin D3. Am J Physiol Gastrointest Liver Physiol. 1986;251(1):G90-5.36.

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

“…OVX also resulted in a non-significant trend towards lower whole-body phosphorus and calcium balance. In a separate study of Cy/+ and WT male rats, we found that phosphorus and calcium balance are also marginally lower in Cy/+ males with CKD compared to normal WT controls 44 . The lower phosphorus and calcium balance in the present study is likely reflective of the loss of bone mass in the OVX rats compared with Sham.…”

Adverse Effects of Autoclaved Diets on the Progression of Chronic Kidney Disease and Chronic Kidney Disease-Mineral Bone Disorder in Rats

“…Composition of the diets is in online supplementary Table 1. CKD and NL were given 3 different diets (n = 8-11 rats per group): (1) AC group: AC grain diet from birth to 28 week, studied at Indiana, (2) AC + Casein group: AC grain diet until 17 weeks then casein diet until 28 weeks, studied at Indiana, (3) Non-AC + Casein group: Non-AC grain from birth to 16 weeks then switched to casein diet until 30 week of age, studied at Purdue [8]. All groups had access to water and food ad libitum light-dark cycle from 6 a.m. to 6 p.m. At the end of the studies, rats were anesthetized with isoflurane, the thoracic cavity was opened, blood collected from the vena cava resulting in death, and intestinal tissues were collected (online suppl.…”

“…For the AC and AC + Casein groups, at 28 weeks, duodenum and jejunum were dissected according to Moe et al [4] and for the Non-AC + Casein according to Vorland et al [8]. Tissues were flushed with 0.9% saline using a gavage needle to remove luminal contents, cut transversally with scissors, the mucosa scraped with microscope cover slip, and the tissue placed in a microcentrifuge tube and flash-frozen with liquid nitrogen.…”

Phosphate Balance and CKD–Mineral Bone Disease

“…Dietary phosphate is absorbed passively via the nonsaturable paracellular pathway and actively via the saturable transcellular pathway. 54 , 117 , 118 , 119 Although it was previously believed that the active transcellular phosphate transport pathway was responsible for the majority of phosphate absorption, there is a growing body of evidence that the paracellular pathway is the dominant site of gastrointestinal phosphate absorption when luminal phosphate concentrations are high, 23 , 120 , 121 consistent with the consumption of a Western diet. 110 The paracellular route, in which phosphate passes through the tight junctions between the cell membranes, is the major phosphate absorption pathway under normal dietary conditions that contain high amounts of phosphate.…”

“… 110 The paracellular route, in which phosphate passes through the tight junctions between the cell membranes, is the major phosphate absorption pathway under normal dietary conditions that contain high amounts of phosphate. 120 , 121 , 122 , 123 Given this new knowledge and the understanding that maladaptive hyperabsorption of phosphate limits the efficacy of low phosphate diets and phosphate binders, 21 , 22 there is a call for new therapies that leverage these data to effectively control phosphate and avoid the negative outcomes associated with hyperphosphatemia and CKD-MBD.…”