Graduation date: 1967

Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Background: Fibroblast growth factor 23 (FGF23) is the earliest marker of disturbed mineral metabolism as renal function decreases. Its serum levels are associated with mortality in dialysis patients, persons with chronic kidney disease (CKD) and prevalent cardiovascular disease (CVD), and it is associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy in the general population. The primary aim of this study is to examine the association between FGF23 and mortality, in relation to renal function in the community. A secondary aim is to examine the association between FGF23 and CVD related death. Methods: The population-based cohort of MrOS Sweden included 3014 men (age 69-81 years). At inclusion intact FGF23, intact parathyroid hormone (PTH), 25 hydroxyl vitamin D (25D), calcium and phosphate were measured. Mortality data were collected after an average of 4.5 years follow-up. 352 deaths occurred, 132 of CVD. Association between FGF23 and mortality was analyzed in quartiles of FGF23. Kaplan-Meier curves and Log-rank test were used to examine time to events. Cox proportional hazards regression was used to examine the association between FGF23, in quartiles and as a continuous variable, with mortality. The associations were also analyzed in the sub-cohort with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m(2). Results: There was no association between FGF23 and all-cause mortality, Hazard ratio (HR) 95% confidence interval (CI): 1.02 (0.89-1.17). For CVD death the HR (95% CI) was 1.26 (0.99 - 1.59)/(1-SD) increase in log(10) FGF23 after adjustment for eGFR, and other confounders. In the sub-cohort with eGFR > 60 ml/min/1.73 m(2) the HR (95% CI) for CVD death was 55% (13-111)/(1-SD) increase in log(10) FGF23. Conclusions: FGF23 is not associated with mortality of all-cause in elderly community living men, but there is a weak association with CVD death, even after adjustment for eGFR and the other confounders. The association with CVD death is noticeable only in the sub-cohort with preserved renal function.

Typescript. / Thesis (Ph. D.)--University of Hawaii, 1965. / Bibliography: leaves 138-147. / vii, 147 l mounted illus., tables

Disturbances in mineral metabolism contribute to vascular calcification and mortality risk in chronic kidney disease (CKD). Serum levels of fibroblast growth factor (FGF)23, a bone derived, phosphaturic peptide, are associated with cardiovascular mortality in CKD. Membrane bound klotho(KL) is an obligate co receptor for FGF23 signaling in the kidney. To study aspects of FGF23 in mild to moderate impairment of renal function we have analyzed FGF23, estimated glomerular filtration rate (eGFR), parathyroid hormone(PTH), 1,25 (OH)2 vitamin D (1,25D), calcium and phosphate in one patient with a FGF23 producing tumor, before and after tumor removal (study 1), in 72 CKD patients with varying degree of renal dysfunction (study 2), in 9 healthy kidney donors, before and after nephrectomy (study 3). We also analyzed FGF23 (study 4), and performed genotyping of 27 single nucleotide polymorphisms (SNP) of the KL gene (study 5) in 2838 elderly Swedish men (MrOs study) and examined the association with mortality. FGF23 normalizes in 30-45 minutes after removal of a FGF23 producing tumor (study 1). 1,25D increases in hours and remains elevated months, even when the other parameters have normalized. FGF23 increase early in CKD, initially slowly, in correlation with PTH, but exponentially when hyperphosphatemia ensues (study 2). After unilateral nephrectomy (study 3) mineral homeostasis remain stable, initially due to a rise in PTH and later to an increase in FGF23. FGF23 levels are not correlated with mortality in elderly men after adjustment for eGFR, but with mortality due to cardiovascular disease, even in persons with normal eGFR (study 4). Polymorphism of the KL gene do not correlate with increased mortality risk in elderly men (study 5), but there is a modulating effect on FGF23 levels. FGF23 is of importance in maintaining phosphate homeostasis as renal function declines. It is co regulated with PTH until advanced renal dysfunction, and adjust the 1,25D to the actual GFR. FGF23 is associated with cardiovascular mortality. Further studies are needed to determine the mechanism, and if reduction of FGF23 by reducing phosphate intake may be beneficial even in persons with mild to moderate renal function.

Thesis (M.Sc.) --University of Adelaide, 1958.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

Thesis (M. Inst. Agrar.)(Animal Production)--University of Pretoria, 2006. / Includes summary. Includes bibliographical references. Available on the Internet via the World Wide Web.

No description available.

<p> Intestinal phosphorus absorption is a key contributor to the body phosphorus pool, but much is unknown regarding physiological adaptations in intestinal phosphorus absorption that occur in vivo. We sought to measure changes in intestinal phosphorus absorption efficiency and phosphorus balance in adolescent females and in rats in response to several factors, using physiologically relevant assessment approaches including whole-body phosphorus balance techniques and <i>in situ</i> ligated intestinal loop absorption methods.</p> <p> We first assessed phosphorus balance and net phosphorus absorption in female adolescents from a controlled crossover study with two levels of calcium intake. Despite an increased calcium intake of 600 mg/day, there was no change in phosphorus balance, nor a significant change in net phosphorus absorption.</p> <p> Next, we measured intestinal phosphorus absorption efficiency with the <i>in situ</i> ligated loop method in healthy Sprague Dawley rats as well as the Cy/+ rat model of progressive kidney disease. We found 10-week-old healthy rats had a small but higher absorption efficiency of phosphorus compared to 20- and 30-week-old rats, while 20-week Cy/+ rats had higher absorption efficiency than 30-week-old. Each of these results corresponded to net phosphorus absorption from balance as well as the concentration of 1,25-dihydroxyvitamin D3. In healthy rats, there was no effect of altering the level of phosphorus in the diet on absorption efficiency. In Cy/+ rats, kidney disease produced a small <i>increase</i> in absorption efficiency, contrary to the predicted decrease that would occur with lower 1,25-dihydroxyvitamin D3 observed in CKD. Gene expression of the major intestinal phosphate transporter, NaPi-2b, largely followed absorption patterns.</p> <p> The utility of the Cy/+ model is limited to males as females do not begin to show signs of progressive kidney decline until a much older age. Therefore, we sought to test whether ovariectomy would accelerate kidney disease in Cy/+ females, with the aim of establishing a postmenopausal model of progressive kidney disease. Our results show that kidney disease is not accelerated by ovariectomy in this rat strain, as measured by kidney weight and biochemistries including blood urea nitrogen, creatinine, creatinine clearance, and plasma phosphorus and calcium.</p> <p> Our results utilizing <i>in situ</i> absorption measures as well as net absorption of phosphorus suggest that some of the factors that are understood to influence the intestinal absorption of phosphorus do not have a significant influence in a physiological context.</p>