The ‘Phosphatonins’ and the regulation of phosphorus homeostasis

Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic Rochester, Mayo College of Medicine, MN 55905, USA.
American journal of physiology. Renal physiology (Impact Factor: 3.25). 01/2006; 289(6):F1170-82. DOI: 10.1152/ajprenal.00072.2005
Source: PubMed


Phosphate ions are critical for normal bone mineralization, and phosphate plays a vital role in a number of other biological processes such as signal transduction, nucleotide metabolism, and enzyme regulation. The study of rare disorders associated with renal phosphate wasting has resulted in the discovery of a number of proteins [fibroblast growth factor 23 (FGF-23), secreted frizzled related protein 4 (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF 7 (FGF-7)] that decrease renal sodium-dependent phosphate transport in vivo and in vitro. The "phosphatonins," FGF-23 and sFRP-4, also inhibit the synthesis of 1alpha,25-dihydroxyvitamin D, leading to decreased intestinal phosphate absorption and further reduction in phosphate retention by the organism. In this review, we discuss the biological properties of these proteins, alterations in their concentrations in various clinical disorders, and their possible physiological role.

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    • "Fibroblast growth factor 23 (FGF23) plays a central role in mineral and bone disorders associated with chronic kidney disease (CKD-MBD) [1]. FGF23 levels are elevated early in CKD and increase as the disease progresses [2]. "
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    ABSTRACT: BackgroundHigh levels of circulating fibroblast growth factor 23 (FGF23) are associated with chronic kidney disease (CKD) progression and high mortality. In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment (PREFECT) study, we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3.MethodsThirty-five individuals were randomized to lanthanum carbonate 3000 mg/day (n = 23) or placebo (n = 12) for 12 weeks. Levels of intact FGF23 (iFGF23), C-terminal FGF23, serum and urinary phosphate and calcium, intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed.ResultsThe median age was 65 years in the lanthanum group and 73 years in the placebo group; 58.8% and 41.7% were men, respectively. No significant difference was seen in mean iFGF23 between groups at week 12. There was, however, a transient reduction from baseline in iFGF23 in the lanthanum group at week 1, from 70.5 pg/ml to 51.9 pg/ml, which was not seen in the placebo group; this between-group difference in percentage change from baseline was significant in post hoc analyses (p = 0.0102). Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12.ConclusionsReducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3, although phosphaturia decreased. This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD.Trial NCT01128179, 20 May 2010.
    BMC Nephrology 05/2014; 15(1):71. DOI:10.1186/1471-2369-15-71 · 1.69 Impact Factor
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    • "At the end, the combination of renal phosphate wasting and calcitriol deficiency leads to osteomalacia, generalized disturbances in skeletal mineralization and thus to an increased fracture risk in patients with TIO [7]. This is caused by factors secreted by the tumors, so-called phosphatonins [8]. The most commonly found and best-characterized phosphatonin in TIO is FGF23 [5] [9]. "
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    ABSTRACT: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia and low calcitriol levels as well as clinical symptoms like diffuse bone and muscle pain, fatigue fractures or increased fracture risk. Conventional imaging methods, however, often fail to detect the small tumors. Lately, tumor localization clearly improved by somatostatin-receptor (SSTR) imaging, such as octreotide scintigraphy or octreotide SPECT/CT. However, recent studies revealed that still a large number of tumors remained undetected by octreotide imaging. Hence, studies focused on different SSTR imaging methods such as 68Ga DOTA-NOC, 68Ga DOTA-TOC and 68Ga DOTA-TATE PET/CT with promising first results. Studies comparing different SSTR imaging methods for tumor localization in TIO are rare and thus little is known about diagnostic alternatives once a particular method failed to detect a tumor in patients with TIO.
    Bone 04/2014; 64. DOI:10.1016/j.bone.2014.04.016 · 3.97 Impact Factor
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    • "Phosphorus has a number of key physiological functions including its roles in bone mineralization and as an important component of nucleic acids and cellular membrane [14]. This mineral also biologically interacts with calcium and vitamin D [15]. "
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    ABSTRACT: We aimed to investigate the effect of dietary intake of micronutrients that are metabolized and excreted via the urinary tract on bladder cancer risk. A semi-quantitative 322 item food frequency questionnaire (FFQ) was used to collect dietary data from 200 bladder cancer cases and 386 control subjects participating in the Belgian case-control study on bladder cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age, sex, smoking characteristics, occupational exposures, and energy intake. We observed a positive association between calcium intake and bladder cancer (OR: 1.77; 95% CI: 1.00-3.15; p-trend = 0.049) and increased odds, although not statistically significant, for highest tertile of phosphorus intake (OR: 1.82; 95% CI: 0.95-3.49; p-trend = 0.06). We identified possible modification of the effects of both calcium and phosphorus by level of magnesium intake. Increased odds of bladder cancer were also observed for participants with highest intake of phosphorus and lowest intake of vitamin D (OR: 4.25; 95% CI: 1.44-12.55) and among older participants with the highest intakes of calcium (OR: 1.90; 95% CI: 1.08-3.36) and phosphorus (OR: 2.02; 95% CI: 1.05-3.92). The positive associations we observed between bladder cancer and intake of calcium and phosphorus require confirmation by other studies. The balances between inter-related micronutrients also warrant further examination.
    Cancer Causes and Control 03/2011; 22(3):469-78. DOI:10.1007/s10552-010-9718-z · 2.74 Impact Factor
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