Browsing by Author "Gallant, Kathleen M. Hill"

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    Dietary Phosphorus and FGF23: Is More Restriction Better?
    (American Society of Nephrology, 2019-10-01) Gallant, Kathleen M. Hill; Medicine, School of Medicine
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    Effect of dietary phosphorus intake and age on intestinal phosphorus absorption efficiency and phosphorus balance in male rats
    (PLOS, 2018-11-19) Vorland, Colby J.; Lachcik, Pamela J.; Aromeh, Loretta O.; Moe, Sharon M.; Chen, Neal X.; Gallant, Kathleen M. Hill; Anatomy and Cell Biology, IU School of Medicine
    Intestinal phosphorus absorption is an important component of whole-body phosphorus metabolism, and limiting dietary phosphorus absorption is particularly of interest as a therapeutic target in patients with chronic kidney disease to manage mineral bone disorders. Yet, mechanisms and regulation of intestinal phosphorus absorption have not been adequately studied and discrepancies in findings exist based on the absorption assessment technique used. In vitro techniques show rather consistent effects of dietary phosphorus intake level and age on intestinal sodium-dependent phosphate transport. But, the few studies that have used in vivo techniques conflict with these in vitro studies. Therefore, we aimed to investigate the effects of dietary phosphorus intake level on phosphorus absorption using the in situ ligated loop technique in three different aged rats. Male Sprague-Dawley rats (n = 72), were studied at 10-, 20-, and 30-weeks-of-age on a low (0.1%), normal (0.6%), or high (1.2%) phosphorus diet in a 3x3 factorial design (n = 8/group). Rats were fed their assigned diet for 2-weeks prior to absorption testing by jejunal ligated loop as a non-survival procedure, utilizing 33P radioisotope. Metabolic cages were used for determination of calcium and phosphorus balance over the final four days prior to sacrifice, and blood was collected at the time of sacrifice for biochemistries. Our results show that phosphorus absorption was higher in 10-week-old rats compared with 20- and 30-week-olds and this corresponded to higher gene expression of the major phosphate transporter, NaPi-2b, as well as higher whole-body phosphorus balance and net phosphorus absorption. Dietary phosphorus intake level did not affect jejunal phosphorus absorption or NaPi-2b gene expression. Our results contrast with studies utilizing in vitro techniques, but corroborate results of other rodent studies utilizing in situ or in vivo methods. Thus, there is need for additional studies that employ more physiological methods of phosphorus absorption assessment.
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    Effects of Excessive Dietary Phosphorus Intake on Bone Health
    (Springer Nature, 2017-10) Vorland, Colby J.; Stremke, Elizabeth R.; Moorthi, Ranjani N.; Gallant, Kathleen M. Hill; Medicine, School of Medicine
    PURPOSE OF REVIEW: The purpose of this review is to provide an overview of dietary phosphorus, its sources, recommended intakes, and its absorption and metabolism in health and in chronic kidney disease and to discuss recent findings in this area with a focus on the effects of inorganic phosphate additives in bone health. RECENT FINDINGS: Recent findings show that increasing dietary phosphorus through inorganic phosphate additives has detrimental effects on bone and mineral metabolism in humans and animals. There is new data supporting an educational intervention to limit phosphate additives in patients with chronic kidney disease to control serum phosphate. The average intake of phosphorus in the USA is well above the recommended dietary allowance. Inorganic phosphate additives, which are absorbed at a high rate, account for a substantial and likely underestimated portion of this excessive intake. These additives have negative effects on bone metabolism and present a prime opportunity to lower total phosphorus intake in the USA. Further evidence is needed to confirm whether lowering dietary phosphorus intake would have beneficial effects to improve fracture risk.
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    Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years
    (Wiley, 2017-07) Kindler, Joseph M.; Pollock, Norman K.; Laing, Emma M.; Oshri, Assaf; Jenkins, Nathan T.; Isales, Carlos M.; Hamrick, Mark W.; Ding, Ke-Hong; Hausman, Dorothy B.; McCabe, George P.; Martin, Berdine R.; Gallant, Kathleen M. Hill; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.; Department of Medicine
    IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.
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    Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease–Mineral Bone Disorder
    (Wiley, 2019) Vorland, Colby J.; Biruete, Annabel; Lachcik, Pamela J.; Srinivasan, Shruthi; Chen, Neal X.; Moe, Sharon M.; Gallant, Kathleen M. Hill; Medicine, School of Medicine
    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 1,25OH2D, 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 1,25OH2D 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.
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    Phosphorus Balance in Adolescent Girls and the Effect of Supplemental Dietary Calcium
    (Wiley, 2018) Vorland, Colby J.; Martin, Berdine R.; Weaver, Connie M.; Peacock, Munro; Gallant, Kathleen M. Hill; Medicine, School of Medicine
    There are limited data on phosphorus balance and the effect of dietary calcium supplements on phosphorus balance in adolescents. The purpose of this study was to determine phosphorus balance and the effect of increasing dietary calcium intake with a supplement on net phosphorus absorption and balance in healthy adolescent girls. This study utilized stored urine, fecal, and diet samples from a previously conducted study that focused on calcium balance. Eleven healthy girls ages 11 to 14 years participated in a randomized crossover study, which consisted of two 3-week periods of a controlled diet with low (817 ± 19.5 mg/d) or high (1418 ± 11.1 mg/d) calcium, separated by a 1-week washout period. Phosphorus intake was controlled at the same level during both placebo and calcium supplementation (1435 ± 23.5 and 1453 ± 28.0 mg/d, respectively, p = 0.611). Mean phosphorus balance was positive by about 200 mg/d and was unaffected by the calcium supplement (p = 0.826). Urinary phosphorus excretion was lower with the calcium supplement (535 ± 42 versus 649 ± 41 mg/d, p = 0.013), but fecal phosphorus and net phosphorus absorption were not significantly different between placebo and calcium supplement (553 ± 60 versus 678 ± 63 versus mg/d, p = 0.143; 876 ± 62 versus 774 ± 64 mg/d, p = 0.231, respectively). Dietary phosphorus underestimates using a nutrient database compared with the content measured chemically from meal composites by ∼40%. These results show that phosphorus balance is positive in girls during adolescent growth and that a calcium dietary supplement to near the current recommended level does not affect phosphorus balance when phosphorus intake is at 1400 mg/d, a typical US intake level.
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    Plant-Based Diets in CKD
    (American Society of Nephrology, 2019-01-07) Clegg, Deborah J.; Gallant, Kathleen M. Hill; Medicine, School of Medicine