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Item Associations between Intake of Calcium, Magnesium, and Phosphorus and Risk of Pancreatic Cancer: A Population-Based, Case-Control Study in Minnesota(Cambridge UP, 2021) Fan, Hao; Yu, Yunpeng; Nan, Haocheng; Hoyt, Margaret; Reger, Michael K.; Prizment, Anna; Anderson, Kristin E.; Zhang, Jianjun; Epidemiology, School of Public HealthExperimental studies suggest that abnormal levels of calcium, magnesium, and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994-1998. Cases of pancreatic cancer (n150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n459) were randomly selected from the general population and frequency matched to cases by age, sex, and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of calcium (936 vs. 1026 mg/day) and dietary intake of magnesium (315 vs. 331 mg/day) and phosphorus (1350 vs. 1402 mg/day) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of calcium, magnesium, and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of calcium, magnesium, and phosphorus were significantly associated with the risk of pancreatic cancer.Item Attributes of Organic Phosphorus Exported from a Central Indiana Agricultural Watershed: Effects of Season and Hydrologic Flowpath(2023-05) Pitcock, Rebecca Jo; Jacinthe, Pierre-Andre; Filippelli, Gabriel; Wang, LixinThe export of phosphorus (P) from agricultural watersheds has been extensively investigated but monitoring efforts have generally focused on inorganic P (Pi or soluble reactive phosphorus [SRP]), the P fraction thought to be immediately available to algae. However, in settings where no-till management is implemented and organic matter accumulates on soil surface, the amount of organic P (Po) in agricultural drainage waters can be significant and may represent another important P source to fuel algal growth in receiving water bodies. From a 2018 monitoring study at a Central Indiana agricultural watershed, measured total P and SRP loss amounted to 1.22 and 0.17 kg P/ha/year, respectively, indicating that the bulk (84%) of P exported from that watershed was in organic form. Results also showed that tile drainage was the main pathway for P transport (96% of Po loss). In light of these observations, the bioavailability of Po in agricultural drainage waters was investigated in 2019, and the effect of hydrologic flow path (surface versus subsurface flow) on the biochemical attributes of Po was examined. In these assessments, the iron strip method and a suite of enzymatic assays were used to gain a better understanding of the chemical composition of the exported Po. Higher concentration of labile Po was consistently measured in tile discharge than in surface runoff (59% versus 38% of the total bioavailable P). Further, the concentration of EHP (enzymatically hydrolysable P), in the form of monoester, diester, and phytate compounds, was highest during the summer season, for both tile and surface pathways. This elevated bioavailability of Po during the summer is a concern because, in combination with favorable water temperature and solar radiation during that period, this could lead to enhanced Po mineralization and release of Pi, resulting in further algal proliferation and continued degradation of water quality. Considering the high prevalence of tile drainage in agricultural landscapes of the US Midwest, this finding underscores the need for further investigation of the impact of land management and climate on the speciation and bioavailability of Po in the region’s agricultural waters.Item Carbon and Phosphorus Cycling in Arabian Sea Sediments across the Oxygen Minimum Zone(Longdom Publishing, 2017-11-09) Filippelli, Gabriel M.; Cowie, Gregory L.; Earth and Environmental Sciences, School of ScienceSeveral studies have focused on carbon, oxygen, and phosphorus dynamics across the modern oxygen minimum zone (OMZ) to constrain how signals of modern systems get “locked in” upon burial. In this study, a sequential phosphorus fractionation technique was applied to surficial and sub-surface sediments from stations at depths spanning the OMZ on the Pakistan margin of the Arabian Sea in order to test the oxygen-carbon-phosphorus connection in modern marine sediments. Some early diagenetic loss of phosphorus compared to organic carbon was observed, but a significant portion of the released phosphorus was retained by uptake on oxyhydroxides and by the formation of an authigenic phosphorus-bearing phase. This process is unaffected by station location relative to the OMZ, and results in an effective organic carbon-to-reactive-phosphorus sediment ratio that is close to the average observed for open-ocean sediments, regardless of bottom water oxygen content.Item A case of calciphylaxis in a patient with hypoparathyroidism and normal renal function(American Association of Clinical Endocrinologists, 2014-06-01) Erdel, Blake L.; Juneja, Rattan; Evans-Molina, Carmella; Department of Medicine, IU School of MedicineOBJECTIVE: To present the case of a patient with a history of thyroid cancer, postsurgical hypoparathyroidism, chronic calcitriol use, and normal renal function who presented with painful skin lesions secondary to calciphylaxis. METHODS: We describe the history, biochemistry, histopathology, evaluation, and management of this patient. RESULTS: A 47-year-old female with hypoparathyroidism, chronically treated with calcitriol and calcium, presented with exquisitely painful skin ulcerations. Four months prior to the onset of symptoms, she had initiated warfarin therapy for atrial fibrillation. Review of laboratory data from the past year revealed elevated calcium and phosphorus levels. A diagnosis of calciphylaxis was made based upon pathologic evaluation of a skin biopsy. Management included titration of calcitriol and calcium to maintain serum calcium and phosphate levels in the low-normal range. Sodium thiosulfate was administered at a dose of 25 mg intravenously 3 times a week with some resolution in the patient's pain. Unfortunately, the patient battled recurrent bacteremia and sepsis, presumably related to her calciphylaxis wounds, and ultimately succumbed to complications from sepsis. CONCLUSION: Although calciphylaxis is typically associated with renal insufficiency and secondary hyperparathyroidism, we highlight the case of a patient with normal renal function and hypoparathyroidism. Patients treated with chronic calcitriol should have serum calcium and phosphorus monitored closely and may benefit from non-calcium-based phosphate binders if hyperphosphatemia becomes unavoidable. This is especially important in the presence of other risk factors for calciphylaxis, including warfarin use.Item Dietary Phosphorus Levels Influence Protein-Derived Uremic Toxin Production in Nephrectomized Male Rats(MDPI, 2024-06-08) Cladis, Dennis P.; Burstad, Kendal M.; Biruete, Annabel; Jannasch, Amber H.; Cooper, Bruce R.; Hill Gallant, Kathleen M.; Nutrition and Dietetics, School of Health and Human SciencesGut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.Item Effect of Soil Type and Fertilizer Application Timing on Phosphorus Leaching From Gypsum-Treated Agricultural Soils(2020-12) Cox, Kristiana; Jacinthe, Pierre-Andre; Wang, Lixin; Gilhooly, William P., IIIPhosphorus is an essential plant nutrient and an important contributor to the eutrophication of aquatic ecosystems. Studies have shown that gypsum (CaSO4∙H2O) applications can potentially reduce phosphorus export from agricultural fields. Most studies have examined the effect of gypsum application rates on treatment effectiveness, but limited research has been conducted to determine how the timing of gypsum application can affect soil phosphorus mobility and phosphorus leaching. A greenhouse experiment was conducted to address this question and further our understanding of the effect of gypsum addition on soil phosphorus chemistry. For the experiment, two soil types with different background phosphorus levels (low P, high P), and three different time intervals between gypsum and phosphorus fertilizer application (2, 28 and 56 days) were applied. A total of 18 soil columns (L: 15 cm; diam: 10 cm) packed with sieved soil were treated with gypsum (3.9 g) and separated into three sets corresponding to each of the phosphorus application times. An equal number of columns not treated with gypsum were also included to serve as controls. Phosphorus fertilizer (0.34 mg P cm-1) was added as KH2PO4 solution. Rainwater (58 mL) was applied every 2-4 days to generate leachate that was collected and analyzed for ortho-P, total P, and SO4-2. At the end of each time series, the set of soil columns were sliced into 2-4 cm increments, and water extractable and bicarbonate extractable phosphorus (Olsen-P) was determined to examine downward phosphorus movement. Results of the study showed that Olsen-P levels were not affected by the gypsum treatment, indicating no interference of gypsum treatment with the P-supplying capacity of soils. The gypsum treatment reduced water-extractable P levels in the high-P soil, but treatment effect was not significant in the low-P soil. Likewise, in the high-P soil, gypsum treatment resulted in leachate ortho-P reduction during the second and third period of collection. For the low-P soil, there was no significant reduction in ortho-P. Overall, these results indicated that the beneficial effect of gypsum on phosphorus export from agricultural fields is dependent on soil-P status and time interval between gypsum amendment and P fertilizer application.Item 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 MedicinePURPOSE 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.Item FGF23 and Associated Disorders of Phosphate Wasting(YS Medical Media, 2019-09-01) Gohil, Anisha; Imel, Erik A.; Pediatrics, School of MedicineFibroblast growth factor 23 (FGF23), one of the endocrine fibroblast growth factors, is a principal regulator in the maintenance of serum phosphorus concentration. Binding to its cofactor αKlotho and a fibroblast growth factor receptor is essential for its activity. Its regulation and interaction with other factors in the bone-parathyroid-kidney axis is complex. FGF23 reduces serum phosphorus concentration through decreased reabsorption of phosphorus in the kidney and by decreasing 1,25 dihydroxyvitamin D (1,25(OH)2D) concentrations. Various FGF23-mediated disorders of renal phosphate wasting share similar clinical and biochemical features. The most common of these is X-linked hypophosphatemia (XLH). Additional disorders of FGF23 excess include autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia, and tumor-induced osteomalacia. Treatment is challenging, requiring careful monitoring and titration of dosages to optimize effectiveness and to balance side effects. Conventional therapy for XLH and other disorders of FGF23-mediated hypophosphatemia involves multiple daily doses of oral phosphate salts and active vitamin D analogs, such as calcitriol or alfacalcidol. Additional treatments may be used to help address side effects of conventional therapy such as thiazides to address hypercalciuria or nephrocalcinosis, and calcimimetics to manage hyperparathyroidism. The recent development and approval of an anti-FGF23 antibody, burosumab, for use in XLH provides a novel treatment option.Item Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer(Wolters Kluwer, 2021) Stremke, Elizabeth R.; Wiese, Gretchen N.; Moe, Sharon M.; Wastney, Meryl E.; Moorthi, Ranjani N.; Hill Gallant, Kathleen M.; Medicine, School of MedicineBackground: Reducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method. Methods: Patients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP). Results: In total, n=8 patients with CKD (eGFR=29-55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant. Conclusions: Intestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined.Item Intestinal Phosphorus Absorption: Recent Findings in Translational and Clinical Research(Wolters Kluwer, 2021) Hill Gallant, Kathleen M.; Vorland, Colby J.; Medicine, School of MedicinePurpose of review: The purpose of this review is to discuss recent findings in intestinal phosphorus absorption pathways, particularly the contributions of paracellular versus transcellular absorption, and the differential findings from studies using in vitro versus in vivo techniques of assessing phosphorus absorption in experimental animal studies. Recent findings: Experimental animal studies show that in vivo effects of low phosphorus diets, 1,25D, and chronic kidney disease on intestinal phosphorus absorption efficiency contradict effects previously established ex vivo/in vitro. Recent in vivo studies also suggest that the paracellular pathway accounts for the majority of phosphorus absorption in animals across very low to high luminal phosphate concentrations. The data from experimental animal studies correspond to recent human studies showing the effectiveness of targeted inhibition of paracellular phosphate absorption. Additionally, recent human studies have demonstrated that NaPi-2b inhibition alone does not appear to be effective in lowering serum phosphate levels in patients with chronic kidney disease. Pursuit of other transcellular phosphate transporter inhibitors may still hold promise. Summary: In vivo animal and human studies have added to our understanding of intestinal phosphorus absorption pathways, regulation, and mechanisms. This is beneficial for developing effective new strategies for phosphate management in patients with chronic kidney disease.